Handbook of Biologically Active Peptides

Handbook of Biologically Active Peptides

2nd Edition - January 26, 2013

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  • Editor: Abba Kastin
  • eBook ISBN: 9780123850966

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Description

Handbook of Biologically Active Peptides, Second Edition, is the definitive, indispensable reference for peptide researchers, biochemists, cell and molecular biologists, neuroscientists, pharmacologists, and endocrinologists. Its chapters are designed to be a source for workers in the field and enable researchers working in a specific area to examine related areas outside their expertise. Peptides play a crucial role in many physiological processes, including actions as neurotransmitters, hormones, and antibiotics. Research has shown their importance in such fields as neuroscience, immunology, pharmacology, and cell biology. The second edition of Handbook of Biologically Active Peptides presents this tremendous body of knowledge in the field of biologically active peptides in one single reference. The section editors and contributors represent some of the most sophisticated and distinguished scientists working in basic sciences and clinical medicine.

Key Features

  • Presents all aspects of biologically active peptides in one resource
  • Features more than 20 sections spanning plant, bacterial, fungal, venom, and invertebrate peptides to general peptides
  • Includes immunological, inflammatory, cancer, vaccine, and neurotrophic peptides
  • Discusses peptide precursors, mRNA distribution, processing, and receptors, not just pathophysiological implications

Readership

Peptide researchers, biochemists, cell and molecular biologists, neuroscientists, pharmacologists, and endocrinologists

Table of Contents

  • Contributors

    Preface to the 1st Edition

    Preface to the 2nd Edition

    Section I: Plant Peptides

    Chapter 1. CLAVATA3

    Discovery

    Structure of the peptide

    Distribution of the mRNA and peptide

    Biological functions

    Receptors and signaling cascades

    References

    Chapter 2. Defense Signal Peptides

    Discovery

    Systemin

    HYPSYS

    Plant Elicitor Peptides (Peps)

    GMSUBPEP

    GMPEP914/890

    Inceptins

    Conclusions

    References

    Chapter 3. DVL/RTFL

    Discovery

    Structure of the peptide

    Distribution of the mRNA/peptide

    Biological function

    Receptors and signaling cascades

    References

    Chapter 4. EPF

    Discovery

    Structure of the Peptide

    Distribution of the mRNA/PEPTIDE

    References

    Chapter 5. IDA/IDL

    Discovery

    Structure of the IDA and IDL Peptides

    Distribution of the mRNA and Biological Function of the IDA and IDL Peptides

    Receptors and Signaling Cascade of IDA

    References

    Chapter 6. LUREs

    Discovery

    Structure of the Peptide

    Distribution of the mRNA/Peptide

    Biological functions

    Receptors and Signaling Cascades

    References

    Chapter 7. Phytosulfokine

    Discovery and Structure of PSK

    Biological Function of PSK In Vitro

    Expression Pattern and In Vivo Function of PSK

    Receptor for PSK and In Planta Function of PSK

    PSY1, A Sulfated Glycopeptide Functionally Similar to PSK

    References

    Chapter 8. POLARIS

    Discovery

    Structure of the Precursor mRNA/Gene

    Distribution of the mRNA

    Processing

    Biological Actions

    References

    Chapter 9. RALF Peptides

    Discovery

    Structure of RALF

    Distribution of the mRNA/Peptide

    Biological Functions

    Receptors and Signaling Cascades

    References

    Chapter 10. Root Meristem Growth Factor

    Discovery of RGF

    Structure, Expression, and Biological Functions of RGF

    Molecular Target of RGF Signaling

    References

    Chapter 11. ROTUNDIFOLIA4

    Discovery

    Structure of the Peptide

    Distribution of the mRNA/Peptide

    Biological Functions

    Receptors and Signaling Cascades

    References

    Chapter 12. SCR

    Discovery of SCR

    Structure of the precursor mRNA gene

    Distribution of the SCR mRNA and the basis of allelic dominance in heterozygotes

    Processing of the SCR protein

    The SCR receptor: the S-locus receptor kinase (SRK)

    Structure of SCR

    Biological actions of SCR and SI signaling

    The SCR-like (SCRL) gene family in plants

    Acknowledgments

    References

    Chapter 13. Stomagen/EPFL9

    Discovery

    Structure of the Peptide

    Distribution of the mRNA/Peptide

    Biological Functions

    Receptors and Signaling Cascades

    References

    Chapter 14. TDIF

    Discovery

    Structure of the peptide

    Distribution of the mRNA/peptide

    Biological functions

    Receptors and signaling cascades

    Acknowledgments

    References

    Section II: Bacterial/Antibiotic Peptides

    Chapter 15. Cathelicidins

    Discovery

    Structure of the Precursor mRNA/Structural Gene

    Distribution of Cathelicidins

    Processing

    Receptors

    Information on Active and/or Solution Conformation

    Biological Functions

    Therapeutic Potential

    Acknowledgments

    References

    Chapter 16. Class II Non-Lantibiotic Bacteriocins

    Background

    Non-Lantibiotic Bacteriocins: Properties and Structural Features

    Other Non-Lantibiotics but Modified Bacteriocins

    Concluding Remarks

    References

    Chapter 17. Colicins

    Discovery and Classification

    Colicin, Immunity, and Lysis Proteins

    The Domain Concept

    Crystal Structures of Colicins (Fig. 1B–E)

    Crystal structures of Colicin–Receptor complexes (Fig. 2)

    Mechanism of import across the outer membrane (Fig. 3)

    Areas of research encompassed by colicin studies

    Acknowledgments

    References

    Chapter 18. Defensins

    Discovery

    Structure of Precursor mRNA and Gene

    Distribution and Expression of the mRNA

    Processing

    Receptors

    Active Conformation

    Biological Actions

    Acknowledgments

    References

    Chapter 19. Lantibiotics

    Discovery

    Structural lanA genes

    Biosynthetic gene clusters

    Biosynthesis of the ring structures

    Processing

    Receptors

    Producer self-protection

    Information on active and/or solution conformation

    Biological activities

    Acknowledgments

    References

    Chapter 20. Microcins

    Discovery and Classification

    Genetic Systems and Biosynthesis

    Immunity of Producing Bacteria to Microcins

    Receptors and Biological Activities

    Structure/Activity Relationships

    Concluding Remarks

    References

    Chapter 21. Nonribosomal Peptide Synthesis

    Introduction

    Monomer Diversity

    Initiation of NRP Assembly

    Elongation during NRP Assembly

    Termination of NRP Assembly

    References

    Chapter 22. Peptaibols

    Introduction

    Characteristic Features of the Peptaibols

    Biological Origins and Biosynthesis of Peptaibols

    Peptaibol Structures

    Functions and Activities of Peptaibols

    Acknowledgments

    References

    Section III: Fungal Peptides

    Chapter 23. Antifungal and Antibacterial Peptides of Fungal Origin

    Introduction

    References

    Chapter 24. Fungal Peptides with Ribonuclease and Ribosome Inactivating Activities

    Mushroom Ubiquitin-Like Peptides

    Mushroom RNases

    Fungal Ribonucleolytic Toxins

    Mushroom Ribosome Inactivating Proteins (RIPs)

    References

    Chapter 25. Fungal Toxins

    Introduction

    Structural Features of the Peptidic Fungal Toxins

    Biosynthesis of Peptidic Fungal Toxins

    Proposed Usage of Fungal Toxins

    Antidotes to Fungal Toxins

    References

    Chapter 26. Plant Antifungal Peptides

    Discovery

    Three-Dimensional Structures of Plant Antifungal Peptides

    Proposed Mechanisms of Action of Plant Antifungal Peptides

    Transgenic Plants Expressing Antifungal Peptides from Plants

    Conclusions

    References

    Chapter 27. Polysaccaride Krestin (PSK) and Polysaccharopeptide PSP

    Discovery

    Strucutre and Chemical Compositions

    Biological Acitvities

    Other Biological Activities

    Conclusions

    References

    Section IV: Invertebrate Peptides

    Chapter 28. AKH/RPCH Peptides

    Discovery

    AKH Structure

    AKH/RPCH Receptors and their Signaling

    Biological Actions

    Acknowledgments

    References

    Chapter 29. Allatostatins

    Discovery

    Structure of Allatostatin Precursors

    Distribution of mRNA and Peptides

    Peptide Processing

    Allatostatin Receptors

    Structure Activity and Active Conformations

    Biological Actions

    Concluding Remarks

    References

    Chapter 30. Allatotropin

    Isolation and Structure of Allatotropin

    The Allatotropin Gene and its Expression

    Biological Activity of Allatotropin

    The Allatotropin Receptor

    References

    Chapter 31. B-Type Allatostatins and Sex Peptides

    Discovery

    Structure of the mRNA/Gene

    Processing of the Precursor

    Distribution of the mRNAS and Peptides

    Receptors and Signaling Cascades

    Biological Actions

    References

    Chapter 32. Crustacean Bioactive Peptides

    Introduction

    Androgenic Gland Hormone (AGH)/Insulin-Related Peptides

    Allatostatins (See Chapter 29)

    CHH-Superfamily

    Corazonin

    Crustacean Cardioactive Peptide (CCAP)

    Diuretic Hormone 31

    Enkephalins (See Chapter 219)

    FMRFamide-Related Peptides (FaRPs) (See Chapter 35)

    GAHKNYLRFamide

    Kinins (See the Kinin Chapters in this and Other Sections of the Book)

    Myosuppressin

    Neuropeptide F-related Peptides

    Orcokinin and Orcomyotropin

    Pigment-Dispersing Hormone (PDH)

    Proctolin

    Pyrokinin

    Red Pigment Concentrating Hormone (RPCH)

    Sifamide

    Sulfakinins

    Tachykinin-Related Peptides

    Conclusions and Perspectives

    References

    Chapter 33. Developmental Peptides: ETH, Corazonin, and PTTH

    Ecdysis-Triggering Hormones

    Corazonin

    Prothoracicotropic Hormone (PTTH)

    References

    Chapter 34. Diuretic/Antidiuretic

    Discovery

    Structure of Precursor mRNAs and Genes

    Distribution of mRNA and Peptides

    Peptide Processing

    Receptors

    Structure–Activity and Active Conformation

    Biological Actions

    Concluding Remarks

    References

    Chapter 35. FMRFamide-Like Peptides (FLPs)

    Discovery

    Structure of the mRNA/Gene

    Processing of the Precursor

    Distribution of mRNA/Peptide

    Receptors and Signaling Cascade

    Biological Actions

    References

    Chapter 36. Free-Living Nematodes

    Introduction

    FMRFamide-Like Peptides (FLPS)

    Neuropeptide-Like Peptides (NLPs)

    Insulins (INSs)

    Antimicrobial Peptides

    Summary

    References

    Chapter 37. FXPRLamide (Pyrokinin/PBAN) Family

    Introduction

    Discovery of the PK/PBAN Family of Peptides: Historical Perspective

    Structure of the mRNA/Gene

    Processing of the Precursor

    Distribution of the Peptide/mRNA

    Receptors and Signaling Cascade

    Signaling Cascade

    Biological Actions

    The PK/PBAN Peptides Family as Potential Targets for Pest Management

    Summary and Future Prospects

    References

    Chapter 38. Insulin-Like Peptides

    Introduction

    Characterization of Insect and Invertebrate ILPs

    Expression, Processing and Secretion of ILPs

    Insulin Signaling

    Regulatory Roles of Insulin-Like Peptides

    Growth and Development

    Ecdysteroid Hormone Production

    Metabolism

    Reproduction

    Diapause

    Behavior

    Immunity

    Aging

    Conclusions

    References

    Chapter 39. Molluscan Bioactive Peptides

    Introduction

    FMRFAMIDE, FMRFAMIDE-Related Peptides (FARPs)

    Insulin-Related Peptides and NPY

    Peptides and Feeding Behavior

    Peptides and Renal Function

    Tachykinin

    Peptides and Reproduction

    APGWAMIDE

    GnRH and Related Peptides

    VP/OP

    References

    Chapter 40. Parasitic Nematode Peptides

    Introduction

    FMRFAMIDE-like Peptides (FLPS)

    Biological Actions of FLPs

    Neuropeptide-Like Peptides (NLPS)

    Insulin-Like Peptides (INSS)

    References

    Chapter 41. Pigment Dispersing Factor

    Discovery

    Structure of the mRNA/Gene

    Processing of the Precursor

    Distribution of the mRNA/Peptide

    Receptors and Signaling Cascades

    Biological Actions

    Acknowledgments

    References

    Chapter 42. Proctolin

    Discovery

    Structure of the MRNA/Gene

    Processing of the Precursor

    Distribution of MRNA/Peptide

    Receptors and Signaling Cascade

    Biological Actions

    References

    Chapter 43. Sulfakinins

    Discovery

    Structure of the mRNA/Gene

    Processing

    Tissue Distribution

    Receptors

    Biological Actions

    References

    Chapter 44. Tachykinin Peptides

    Discovery

    Structure of Precursor mRNAS and Genes

    Distribution of mRNA and Peptides

    Peptide Processing

    Receptors of TKRPs

    Structure Activity and Active Conformation

    Biological Actions

    Concluding Remarks

    References

    Section V: Amphibian/Skin Peptides

    Chapter 45. Bradykinin Peptides

    Discovery and Distribution

    Biosynthesis of Bradykinin and Related Peptides

    Molecular Variants of BK

    Biological Activities

    References

    Chapter 46. Bombesin Peptides

    Introduction

    Amphibian Bombesins

    Amphibian Phyllolitorins

    Ranatensin-Like Peptides

    Gastrin-Releasing Peptide

    Phylogenetic Considerations and Implications for Additional Mammalian Bombesin-Like Peptides

    References

    Chapter 47. Bombinins

    Bombinins: General Features

    Solution Structure

    The Gene Structure of BLPs and Bombinins H

    Biological Properties (Antibacterial, Antifungal, Antiparasitic, and Cytolytic Activities)

    Bombinins H: Mechanism of Action of Antimicrobial Activity

    Acknowledgments

    References

    Chapter 48. Caeruleins

    Introduction

    The Caerulein Peptides

    Acknowledgments

    References

    Chapter 49. Chromogranins/Secretogranins

    Discovery

    Structure and Processing of the Precursors

    Distribution and Regulation of the mRNAs

    Biological Actions

    Acknowledgments

    References

    Chapter 50. Dermaseptins

    The Dermaseptin Superfamily: A Library of Structurally and Functionally Disparate Peptides Originating from a Single Gene Family

    The Dermaseptin Superfamily: Gene Duplication, Focal Hypermutation, and Diversifying Selection

    Antimicrobial Activities of the Preprodermaseptin-Derived Peptides from South American Hylidae Frogs

    Mechanisms of Microbicidal Activity

    The Dermaseptins: Multifunctional Host Defense Peptides

    References

    Chapter 51. Insulin-Releasing Peptides

    Introduction

    Insulinotropic Peptides from Ranidae

    Insulinotropic Peptides from Hylidae

    Insulinotropic Peptides from Bombinatoridae

    Insulinotropic Peptides from Leptodactylidae

    Insulinotropic Peptides from Dicroglossidae

    Insulinotropic Peptides from Pipidae

    Analogs with Increased Insulin-Releasing Activity

    Conclusions

    References

    Chapter 52. Neurohypophysial Peptides

    Discovery

    Distribution of AVT and MT

    Receptor Structure and Distribution

    Major Biological Actions of AVT and MT

    Structure and Function of Hydrins

    References

    Chapter 53. Opioid and Bv8 Peptides

    Opioid Peptides

    Bv8/Prokineticin Family (Swiss-Prot: Q9PW66)

    References

    Chapter 54. Sodefrin and Related Pheromones

    Discovery

    Structure of the Precursor mRNA/Gene

    Distribution of the mRNA

    Processing of the Precursors

    Receptors

    Structure–Activity Relationships

    Biological Actions

    Physiological Implications

    References

    Chapter 55. Tachykinins

    Discovery

    Structure of the Precursor mRNA/Gene

    Processing of the Precursor

    Distribution

    Receptors and Signaling Cascades

    Actions in Amphibians

    Actions of Amphibian TKs in their Species of Origin

    Actions in Mammals

    Pathological Implications

    References

    Chapter 56. Temporins

    Discovery and Distribution

    Biosynthesis

    Molecular Heterogeneity

    Biophysical Properties and Interaction with Membranes

    Biological Activities

    Potential Clinical and Commercial Applications

    Conclusions

    References

    Section VI: Venom Peptides

    Chapter 57. Animal Toxins

    Animal Toxins as Candidate Drugs

    Animal Toxins in Biotechnological Applications

    Maurocalcine, an Animal Toxin that Targets an Intracellular Receptor

    Maurocalcine is a Competitive Cell-Penetrating Peptide

    The Pharmacological Activity of Maurocalcine is Easy to Neutralize

    Maurocalcine Produces Cell Delivery into the Cytoplasm

    Maurocalcine has an Excellent Cell Entry/Toxicity Ratio

    Maurocalcine is a Stable CPP Vector in Vivo

    Maurocalcine Preferentially Targets Some Cell Types and Organs in Vivo

    Concluding Remarks

    References

    Chapter 58. Hymenoptera Insect Peptides

    Introduction

    Peptides from the Venoms of Social Hymenoptera

    Peptide Toxins from Honey Bee Venom

    Peptide Toxins from Bumblebee Venoms

    Peptide Toxins from Social Wasp Venoms

    Peptides from Ant Venoms

    Pathophysiology of Hymenopteran Peptide Toxins

    Acknowledgments

    References

    Chapter 59. Scorpion Peptides

    Introduction

    Mining on Scorpion Venoms

    Documented Molecular Diversity

    Structural and Functional Types

    Concluding Remarks

    Acknowledgments

    References

    Chapter 60. Sea Anemone Peptides

    Introduction

    Sea Anemone Genome

    Other Genomics Analyses

    New Peptides from Anemones

    Structures

    Therapeutic Applications

    Acknowledgments

    References

    Chapter 61. Snail Peptides

    Biodiversity of Venomous Molluscs and Discovery of Their Venom Peptides

    Discovery of Conotoxins

    Precursor Structure, Expression, and Processing: Conotoxin Superfamilies

    Definition of Conotoxin Families, Receptor Targets, and Structures

    Biological Mechanisms: Therapeutic Applications

    Overview of Peptides from Other Venomous Marine Snails

    Perspectives

    Acknowledgments

    References

    Chapter 62. Snake Peptides

    Introduction

    Three-Finger Toxins

    Protease Inhibitor Homologs

    Crotamine-Like Myotoxins

    Sarafotoxins

    CRISP Family Toxins

    Natriuretic Peptides

    Disintegrins

    C-Type Lectins and Lectin-Like Proteins

    Waglerins

    Bradykinin-potentiating peptides

    AVIT peptides

    Cystatins

    Cathelicidins

    Waprins

    Miscellaneous Peptides

    References

    Chapter 63. Spider Peptides

    Introduction

    Methodological Approaches in the Isolation of Spider Venom Peptides

    Structure of the Precursor Spider Venom Peptide and PostTranslational Processing

    Linear Peptides

    Disulfide-Rich Peptides

    Conclusions and Future Directions

    References

    Chapter 64. Targets and Therapeutic Properties

    Cardiovascular Diseases

    Infection, Immunity, and Oncology

    Nervous System

    Metabolic and Other Diseases

    Conclusions

    Acknowledgments

    References

    Chapter 65. Worm Peptides

    Introduction

    Nemertine Neurotoxins

    Nemertine Peptide Cytolysins

    Annelid (Glycera) Neurotoxin

    Annelid Antibacterial Peptide Toxins

    Nematode and Platyhelminth Peptide Cytolysins

    Concluding Comments

    References

    Section VII: Cancer/Anticancer Peptides

    Chapter 66. Adrenomedullin

    Introduction

    Anatomical Sources of AM

    Regulatory Pathway that Stimulate AM Expression

    AM Induced Cell Growth

    AM-Mediated Antiapoptosis

    AM-Regulated Cell Migration/Invasion

    AM Effects on the Immune Response

    AM Stimulates Angiogenesis and Lymphangiogenesis

    AM-Targeted Therapies for Cancer

    AM, Obesity, Diabetes, and Cancer— Axial Link

    Conclusions

    Acknowledgments

    References

    Chapter 67. Angiotensin II/Angiotensin-(1–7)

    Introduction

    Detection of Ang II in Tumor Tissue and Cancer Cell Lines

    Ang II Stimulates Cancer Cell Proliferation

    Ang II Promotes Tumor Angiogenesis

    Effects of Ang II on the Tumor Microenvironment

    Ang II Stimulates Cancer Cell Migration and Invasion

    Ang II Induced Cancer Cell Signaling

    Ang-(1–7) Attenuates Tumor Growth

    Ang-(1–7) Inhibits Tumor Angiogenesis

    Effects of Ang-(1–7) on the Tumor Microenvironment

    Ang-(1–7) Clinical Trials

    Conclusions

    References

    Chapter 68. Apelin

    Introduction

    Role of Apelin in Cancer

    Conclusions

    References

    Chapter 69. Bombesin Peptides

    Introduction

    Bn-Related Peptides (GRP, NMB)

    Acknowledgments

    References

    Chapter 70. Endothelin-1

    Endothelin-1

    ET-1 Associated Signal Transduction Pathways

    ET-1 Expression in Cancer

    Endothelin Receptor Expression in Cancer

    ET-1 as a Mitogen

    ET-1 and Apoptosis

    ET-1 and Angiogenesis

    ET-1 and Tumor Progression/Metastases

    Endothelin Antagonism in vivo

    Clinical Trials

    References

    Chapter 71. Gastrin

    Introduction

    Expression of Gastrins in Normal Tissue

    The Gastrin Receptor(s)

    Expression of Gastrin in Tumors

    Gastrin as a Tumor Growth Factor

    Conclusions

    References

    Chapter 72. Leptin/Adiponectin

    Introduction

    Leptin and Cancer

    Clinical Evidence of Leptin Related to Cancer

    In Vitro Results of Leptin as a Mitogenic Factor

    Systemic Regulation of Leptin on Cancer

    In Vivo Results of Leptin and Cancer

    Adiponectin and Cancer

    Clinical Evidence of Adiponectin Related to Cancer

    Potential Mechanisms of Adiponectin as a Protective Factor of Cancer

    In Vivo Results of Adiponectin and Cancer

    Cancer-Related Polymorphisms of Adiponectin and AdipoR1 Genes

    Interplay between Leptin and Adiponectin

    Summary

    Acknowledgments

    References

    Chapter 73. LHRH Analogs

    Introduction

    Receptors for LHRH-I and LHRH-II

    Signaling mechanisms from LHRH receptors

    Development of Analogs of LHRH

    Agonistic Analogs of LHRH-I

    Mechanism of Biological Action of LHRH and its Agonists

    Applications of Agonists of LHRH-I

    Antagonists of LHRH

    Targeted Cytotoxic Analogs of LHRH

    Mechanism of Action of Cytotoxic LHRH Analogs

    Receptors for LHRH on Human Tumors

    Antitumor effects of Agonists and Antagonists of LHRH—Experimental and Clinical Findings

    Applications of Cytotoxic LHRH Analogs

    Clinical trials with AN-152 (AEZS-108) in Men with Prostate Cancer

    Breast Cancer

    Summary

    Acknowledgments

    References

    Chapter 74. Orexins (Hypocretins)

    Introduction

    Discovery

    Structure of the mRNA/Gene

    Processing of the Precursor

    Distribution of the mRNA/Peptide

    Receptors and Signaling Cascades

    Biological Actions within the Gastrointestinal Tract and the Pancreas

    Pathophysiological Implications

    Conclusions and Perspectives

    References

    Chapter 75. Somatostatin/NPY

    Introduction

    Somatostatin

    NPY

    References

    Chapter 76. VIP/PACAP Receptors

    Introduction

    VPAC1-R

    PAC1-R

    Second Messengers

    Protein Phosphorylation

    Proliferation

    Summary

    Acknowledgments

    References

    Section VIII: Vaccine Peptides

    Chapter 77. Antiadhesin Peptide-Based Vaccines for Pseudomonas aeruginosa

    Significance and Background

    Synthetic Consensus Sequence Peptide-Based Pseudomonas Aeruginosa Vaccines

    Conclusions

    References

    Chapter 78. Lipo-Peptides/Saccharides for Peptide Vaccine Delivery

    Introduction

    Subunit Vaccines

    Lipidation

    Glycolipopeptides

    Conclusions

    References

    Chapter 79. Novel Tumor Derived Peptides in Vaccines

    Introduction

    Antigen Processing and Its Role in Peptide-Based Vaccinology

    Mass Spectrometry and the Identification of T-cell Epitopes

    Synthetic Peptides as Vaccines

    Conclusions

    Acknowledgments

    References

    Chapter 80. Peptide Vaccine for Alzheimer’s Disease

    Introduction

    In vitro modulation of β-amyloid formation

    EFRH Phage Elicits Antibodies Against β-Amyloid Peptide

    Peptides as Vaccines for the Prevention and/or Reduction of Amyloid Plaques in AD Transgenic Mice

    Active Immunization of hAPP Transgenic Mice with EFRH Phage as Peptide Vaccine

    Future Outlook

    Acknowledgments

    References

    Chapter 81. Peptide Vaccines for Myeloid Leukemias

    Introduction

    Leukemia-Associated Antigens (LAAs)

    Vaccination

    Why Peptides?

    BCR-ABL Peptide Vaccine

    WT1 Peptide Vaccine

    PR1 Peptide Vaccine

    Combined PR1 and WT1 Peptide Vaccines

    RHAMM Peptide Vaccine

    Implications and Future Perspectives

    References

    Chapter 82. Peptide Vaccines for Otitis Media

    Disease Target

    Background of Available Therapies

    Why Peptides?

    Our Contributions to the Area

    Future Outlook

    References

    Chapter 83. Therapeutic Peptides Targeting HER-2/neu and VEGF Signaling Pathways in Breast Cancer

    Peptides as Therapeutic Candidates

    HER-2 Signaling Pathways, Cancer, and Strategy for the Design of HER-2 Peptide Mimic

    VEGF, Cancer, and the Design of VEGF Peptide Inhibitor

    Additive/Synergistic Effects of Targeting Both HER-2 and VEGF Pathways in Cancer

    Conclusions

    Acknowledgments

    References

    Chapter 84. Use of Positional Scanning Libraries to Identify Immunologically Relevant Peptides

    Definition of Mixture-Based Libraries

    Use of Positional Scanning Libraries to Determine Antibody Specificity

    Use of Positional Scanning Libraries for T Cell Epitope Mapping

    Use of Positional Scanning Libraries to Identify MHC-Binding Motifs

    Conclusions

    References

    Section IX: Immune/Inflammatory Peptides

    Chapter 85. Anaphylatoxins

    Historical Perspective and Scope

    Precursor mRNA/Gene Structure, Expression, and Regulation of Anaphylatoxins

    Generation of C3A and C5A Anaphylatoxins

    Structure of Anaphylatoxins

    Receptors for Anaphylatoxins

    Biological Actions of Anaphylatoxins

    Pathophysiological Implications of Anaphylatoxins

    Acknowledgments

    References

    Chapter 86. Annexin-A1 Peptide Ac2–26

    Discovery

    Scope of this Chapter

    Discovery of Importance of the N-Terminal Peptide

    The Structure of Anx-A1 and Acetyl 2–26

    Receptors for Anx-A1 and N-Acetyl 2–26

    Biological Properties of the Acetyl-26 Peptide

    Structure–Activity Relationships

    Summary

    References

    Chapter 87. Immunoregulatory Neuropeptides

    Introduction

    Anti-inflammatory Neuropeptides that Regulate the Autoimmune Response

    Induction of Immune Tolerance by Generating Regulatory T-Cells

    Redundant and Pleiotropic Effects on Immune Homeostasis: A Matter of Receptor Specificity and Signaling

    A healthy Immune System Requires a Physiologically Functional Neuropeptide System

    Conclusions

    Acknowledgments

    References

    Chapter 88. Chemerin

    Discovery

    Structure of the mRNA/Gene

    Processing of the Precursor

    Distribution of the mRNA/Peptide

    Receptors and Signaling Cascades

    Biological Actions

    Pathophysiological Implications

    Acknowledgments

    References

    Chapter 89. Chemokines

    Organization of Chemokines

    Structure of Chemokines

    Chemokine Receptors

    Biology of Chemokines

    Chemokines in Host Defense

    Chemokines in Inflammatory Diseases

    Chemokines as Antimicrobial Peptides

    References

    Chapter 90. DP IV/CD26 Effector Peptides

    Introduction

    DP IV/CD26 in the Immune System

    DP IV Effector Peptides

    Primary DP IV Effector Peptides

    Secondary Immunorelevant DP IV peptide substrates

    Peptide Inhibitors of DP IV

    References

    Chapter 91. FPR Ligands

    Introduction

    Formyl Peptide Receptors (FPRs)

    FPR Agonists

    Nonpeptides

    FPR Antagonists

    Perspectives

    Acknowledgments

    References

    Chapter 92. Neuroimmune Peptides

    Introduction

    Acknowledgments

    References

    Chapter 93. Peptide Loading of MHC

    Introduction

    The MHC Locus

    MHC-Class I

    MHC-Class II

    Concluding Remarks

    References

    Chapter 94. Peptide Recognition by T Cells

    Introduction

    Major Histocompatibility Complex Class I and Class II Molecules

    Characteristics of Peptides Presented by MHC-Class I

    Characteristics of Peptides Presented by MHC-Class II

    Biological Roles of MHC-Bound Peptides

    Autoimmune Diseases

    Therapeutic Use of Peptides

    Conclusions

    References

    Chapter 95. RGD Peptides

    Discovery of The Antiadhesive RGD Peptides

    RGD Peptides in Platelet Aggregation

    Biologically Active Conformation of RGD Peptides

    RGD Peptides in Immunological Phenomena

    RGD Peptides and Pathogen Invasions

    RGD Peptides in Other Pathological Phenomena

    Perspectives

    References

    Section X: Brain Peptides

    Chapter 96. Apelin

    Discovery

    Structure of the mRNA/Gene

    Processing of the Precursor

    Distribution of the mRNA/Peptide

    Receptors and Signaling Cascades

    Biological Actions Within the Brain and Pituitary Gland

    Peripheral Cardiovascular Actions

    Pathophysiological Implications

    References

    Chapter 97. BNP/CNP

    Discovery

    Structure of the mRNA/Gene

    Processing of the Precursor

    Distribution of the mRNA/Peptide

    Receptors and Signaling Cascades

    Biological Actions Within the Brain and Pituitary

    Pathophysiological Implications

    References

    Chapter 98. CART

    Discovery

    Structure of the CART Precursor mRNA and CART Gene

    Processing of CART Peptides

    Distribution of CART mRNA and Peptides

    Receptors and Signaling Cascades

    Biological Actions of CART Peptides within the Brain and Pituitary

    Pathophysiological Implications

    References

    Chapter 99. CCK

    Structure of the Precursor mRNA/Gene

    Distribution of CCK

    Processing of the Precursor (see Peptide Biosynthesis/Processing section of this book)

    References

    Chapter 100. CGRP/Adrenomedullin

    Discovery

    Structure of the Precursor mRNA/Gene

    Distribution of the mRNA/Peptide

    Processing of the Precursor

    Receptors and Signaling Cascades

    Peptide Conformation

    Biological Actions within the Brain

    Pathophysiological Implications

    Acknowledgments

    References

    Chapter 101. CRH Family

    Discovery

    Precursor Gene and cDNA Structure

    Distribution and Expression of mRNA

    Processing of Preprohormone

    Receptors and Binding Proteins

    Biological Actions in the Central Nervous System

    Pathophysiological Implications

    References

    Chapter 102. Endozepines

    Discovery

    Structure of DBI mRNA/Gene

    Processing of the DBI Precursor

    Distribution of DBI mRNA and Endozepine Immunoreactivity

    Control of Biosynthesis and Release of Endozepines

    Receptors and Signaling Cascades

    Information on Solution Conformation of Endozepines

    Biological Actions of Endozepines within the Brain

    Pathophysiological Implications of Endozepines

    References

    Chapter 103. Galanin and GALP

    Discovery

    Structure of the mRNA/Gene

    Processing of the Peptide Precursor

    Distribution of the mRNA/Peptide

    Receptors and Signaling Cascades

    Biological Actions within the Brain and Pituitary

    Pathophysiological Implications

    References

    Chapter 104. Ghrelin

    Discovery

    Structure of the Ghrelin Gene, mRNA, and Precursor Protein

    Distribution of Ghrelin in the Central Nervous System

    Processing of the Ghrelin Precursor

    Ghrelin Receptor in the Brain

    Biological Actions of Ghrelin Within the Brain

    References

    Chapter 105. GHRH

    Discovery

    Structure of the GHRH mRNA/GENE

    Processing of the GHRH Precursor

    Distribution of the GHRH mRNA/Peptide

    GHRH Receptor and Signaling Cascades

    Biological Actions of GHRH within the Pituitary and The Brain

    Pathophysiological Implications

    References

    Chapter 106. GnRH (LHRH)

    Discovery And Background

    Structure of GnRHs and Their Precursors

    GnRH Distribution

    Processing of The GnRH Precursor

    GnRH Receptors and Signaling Cascades

    Physical Structure of GnRH

    Biological Actions

    Therapeutic Application of GnRH Analogs

    Future Perspectives

    References

    Chapter 107. Gonadotropin-Inhibitory Hormone

    Discovery

    Structure of the mRNA/GENE

    Processing of the Precursor

    Distribution of the mRNA/PEPTIDE

    Receptors and Signaling Cascades

    Biological Actions on the Pituitary and within the Brain

    Pathophysiological Implications

    References

    Chapter 108. Hypocretins (Orexins)

    Discovery

    Structure of the Precursor mRNA/Gene

    Distribution of the mRNA

    Processing of the Precursor

    Receptors and Signaling Cascades

    Information on Active and/or Solution Conformation

    Biological Actions Within the Brain

    Pathophysiological Implications

    References

    Chapter 109. Kisspeptins

    Discovery of the Kiss1 System

    Pathophysiological Implications

    Acknowledgments

    References

    Chapter 110. MCH

    Discovery

    Structure of the Precursor mRNA/Gene

    Processing of the MCH Precursor

    Distribution of the mRNA/Peptides

    Receptors and Signaling Cascades

    MCH-R1 Structure and Signaling

    MCH-R2 Structure and Signaling

    Active Structure of the MCH Peptide and Receptor Conformation

    Biological Actions within the Brain (and Pituitary)

    Pathophysiological Implications

    References

    Chapter 111. Melanocortins

    Discovery

    References

    Chapter 112. MIF-1/Tyr-MIF-1

    Conformation

    References

    Chapter 113. Nesfatin-1

    Discovery

    Structure of the mRNA/GENE

    Processing of the Precursor

    Distribution of the mRNA/peptide

    Receptors and Signaling Cascades

    Biological Actions within the Brain (and Pituitary)

    Pathophysiological Implications

    Acknowledgments

    References

    Chapter 114. Neuromedin U

    Discovery

    Structure of NMU mRNA

    NMU Distribution and Processing

    NMU Receptors

    NMU1R

    Biological Actions of NMU in the Brain

    Comparison of the Biological Actions of NMU and NMS

    Pathophysiological Implications

    References

    Chapter 115. Neuropeptide B/W

    Introduction

    Identification of NPB/W

    Acknowledgments

    References

    Chapter 116. Neuropeptide S

    Discovery

    Structure of the mRNA/gene

    Processing of the Precursor

    Distribution of the mRNA/peptide

    Receptors and Signaling Cascades

    Biological Actions within the Brain

    Pathophysiological Implications

    References

    Chapter 117. Neurotensin/Neuromedin N

    Discovery of Neurotensin

    Structure of the Neurotensin/Neuromedin N Precursor mRNA/gene

    NT/NMN mRNA Expression in Brain

    Processing of the Precursor

    Receptors and Signaling Cascades

    Conformation

    Brain Functions

    Pathophysiological Implications

    References

    Chapter 118. NPY

    Discovery of NPY and Homologs

    Structure of the Precursor mRNA/Gene

    Processing of the NPY Precursor

    Distribution of NPY mRNA and Protein

    Structure of NPY-Like Peptides

    Receptors and Signaling Cascades

    Biological Actions

    Pathophysiological Implications

    Acknowledgment

    References

    Chapter 119. PACAP

    Discovery

    Structure of the mRNA/Gene

    Processing of the Precursor

    Distribution of the mRNA/Peptide

    Receptors and Signaling Cascades

    Biological Actions within the Brain

    Pathophysiological Implications

    References

    Chapter 120. Prolactin-Releasing Peptide

    Discovery

    Structure of the PrRP mRNA/Gene

    Processing of the PrRP Precursor

    Distribution of the mRNA/Peptide

    PrRP Receptors and Signaling Cascades

    Biological Actions of PrRP within the Brain (and Pituitary)

    Pathophysiological Implications

    References

    Chapter 121. Relaxins

    Discovery

    Structure of the mRNA/Gene

    Processing of the Peptide Precursor

    Distribution of the mRNA/Peptide

    Receptors and Signaling Cascades

    Distribution of mRNA/Protein

    Biological Actions within the Brain

    Pathophysiological Implications

    Acknowledgments

    References

    Chapter 122. 26RFa

    Discovery

    Structure of the 26RFa Precursor

    Processing of the Precursor

    Distribution of 26RFa mRNA

    Distribution of GPR103 mRNA and Signaling Cascades

    Solution Conformation

    Structure–Activity Relationships

    Biological Actions within the Brain (and Pituitary)

    Pathophysiological Implications

    Acknowledgments

    References

    Chapter 123. Secretin

    Discovery

    Structure of the mRNA/Gene

    Processing of the Precursor

    Distribution of the mRNA/Peptide

    The Secretin Receptor and its Signaling Cascades

    Biological Actions within the Brain (and Pituitary)

    Pathophysiological Implications

    References

    Chapter 124. Somatostatin/Cortistatin

    Discovery

    Structure of the Precursor mRNA/Genes

    Distribution of the mRNAS and Peptides

    Processing of the Precursors and Degradation of the Peptides

    Receptors and Signaling Cascades

    Information on Active and/or Solution Conformation

    Biological Actions within the Brain and Pituitary

    Pathophysiological Implications

    References

    Chapter 125. Tachykinins

    Discovery

    Structure of the mRNA/Gene

    Processing of the Precursor

    Distribution of the mRNA/Peptide

    Receptors and Signaling Cascades

    Biological Actions within the Brain

    Pathophysiological Implications

    References

    Chapter 126. TRH

    Discovery of TRH

    Structure of the Precursor mRNA/Gene

    Distribution of PreproTRH mRNA and PreproTRH-Derived Peptides

    Processing of the TRH Precursor

    Distribution of TRH Receptors and the TRH Degrading Enzyme

    TRH Receptor Signaling Cascades

    Biological Actions of TRH within the Brain and Pituitary

    Pathophysiological Implications

    References

    Chapter 127. Urotensin II Peptides

    Discovery

    Structure

    Localization

    Receptors and Signaling Cascades

    Biological Actions within The Central Nervous System

    Physiological and Pathophysiological Significance

    References

    Chapter 128. VIP

    Introduction

    Structure of the mRNA/Gene

    Distribution of the mRNA/Peptide

    Receptors and Signaling Cascades

    Biological Action within the Brain (and Pituitary) and Pathophysiological Implications

    References

    Chapter 129. VP/OT

    Discovery and History

    Structure and Regulation of the Precursor mRNAs/Genes (Fig. 1)

    Processing of the Precursors (Fig. 2),

    Distribution of VP and OT Producing Cells; Sites of Release (Figs. 3 and 4)

    Receptors for VP and OT; Signaling Cascades (Fig. 5)

    Biological Actions

    Physiological and Pathological Implications (See Chapters in Cardiovascular and Renal Peptides Section of the Book)

    References

    Section XI: Endocrine Peptides

    Chapter 130. Adiponectin

    Discovery

    The Adiponectin Gene and Protein Structure

    Production of Adiponectin

    Adiponectin Receptors

    Adiponectin Signaling

    Adiponectin and Energy Homeostasis

    Adiponectin and Obesity

    Conclusions

    References

    Chapter 131. Adrenomedullin Peptides

    Introduction

    Pituitary

    Adrenals

    Endocrine Pancreas

    Diffuse Endocrine System of the Gut

    Other Endocrine Organs

    Conclusions

    Acknowledgments

    References

    Chapter 132. Ghrelin

    Introduction

    Ghrelin System in the Pituitary

    Ghrelin System and Thyroid Gland

    Ghrelin System in the Parathyroid Gland

    Ghrelin System in the Testis and Ovary

    Ghrelin System in the Pancreatic Islets

    Ghrelin System in the Adrenal Gland

    Concluding Remarks

    References

    Chapter 133. Leptin

    Introduction

    Regulation of Pancreatic B-cell Functions by Leptin

    Role of Leptin in Regulating Thyroid Functions

    Leptin and the Reproductive System

    Regulation of Adrenal Glands by Leptin

    Conclusions

    References

    Chapter 134. ANP

    Discovery

    Structure of the Precursor mRNA Gene

    Processing

    Release of NPs

    Receptors and Signaling Cascade

    Biological Activities of NPs

    Pathophysiological Implications

    References

    Chapter 135. Neuromedins U/S

    Introduction

    Hypothalamus

    Pituitary Gland

    Thyroid Gland

    Pancreatic Islets

    Adrenal Gland

    Testis

    Ovary

    Conclusions

    References

    Chapter 136. Neuropeptide B/W

    Introduction

    Neuroendocrine Function of NPB/NPW

    Endocrine Function of NPB/W

    Regulation of Feeding and Energy Metabolism by NPW

    Antihyperalgesic Effect of NPB/W

    Acknowledgments

    References

    Chapter 137. Orexins

    Overview of the Structure of Orexins and its Receptors

    Adipose Tissue

    Gastrointestinal Tract

    Hypothalamic–Pituitary–Adrenal Axis

    Adrenal Glands

    Hypothalamic–Pituitary–Thyroid Axis

    Testes and Ovaries

    PANCREATIC ISLETS

    Energy Expenditure

    Physiological Implications

    Conclusions

    References

    Chapter 138. PACAP

    Introduction

    Effects on the Pituitary Gland

    Effects on the Thyroid Gland

    Effects of PACAP on the Endocrine Testis and Ovary

    Effects of PACAP on the ADRENAL GLAND

    Effects of PACAP on Pancreatic Islets

    References

    Section XII: Ingestive Peptides

    Chapter 139. Adiponectin/Resistin

    Adiponectin and Energy Homeostasis

    Rodent versus Human Resistin

    Resistin and Energy Homeostasis

    Conclusions

    Acknowledgments

    References

    Chapter 140. Amylin/CGRP

    Introduction

    Receptors for Amylin and CGRP Action

    Characterization of the Effects of Amylin and CGRP on Eating as Satiating Hormone

    Amylin as an Adiposity Signal

    Eating in Knockout Animals

    Eating in Animals Overexpressing Amylin

    Eating in Animals Deficient of CGRP or Overexpressing CGRP

    Energy Expenditure as Affected by Amylin and CGRP

    Energy Metabolism in Animals with Increased Amylin or CGRP Signaling Propensity

    Regulation of Amylin and CGRP Synthesis and Secretion in Lean and Obese Individuals

    Central Pathways Mediating the Anorectic Effects of Amylin and CGRP

    Phenotype of Amylin Responsive Neurons in The AP

    Intracellular Signaling Pathways in AP Neurons Activated by Amylin

    Projections of AP neurons implicated in amylin’s and CGRP’s effects and hypothalamic involvement in the anorectic action of peripheral amylin.,

    Site of CGRP Action

    Forebrain Effects of Amylin

    Forebrain Effects of CGRP

    Interaction Between Amylin and Estradiol

    Short-term Interaction with Other Hormones Controlling Ingestive Behavior

    Interaction Between Amylin and Leptin

    Role of the VMH in the Leptin and Amylin Interaction

    Interaction between Amylin and Metabolites

    Physiological and Pathophysiological Implications

    Summary

    References

    Chapter 141. Apolipoprotein (apo) A-IV/apoE

    Introduction

    Regulation of apo A-IV and apoE Production

    Peripheral and Neural Networks and Signaling Pathways Affected

    References

    Chapter 142. Bombesin

    Background

    Peripheral Effects of BN-like Peptides on Food Intake

    Central Effects of BN-like Peptides on Food Intake

    Neural Pathways Mediating the Effects of BN-like Peptides

    Contribution of BN Receptor Subtypes to Food Intake Using Genetically Modified Mice

    BN-like Peptides/Receptors and Energy Homeostasis

    ACKNOWLEDGMENT

    References

    Chapter 143. CART

    Introduction

    Effects on Feeding Behavior

    Studies from Genetically Modified Organisms

    Functional Responses in Different Metabolic States

    Neural Networks Involved

    Receptors and Signaling Pathways

    Interactions with Other Systems

    Pathophysiological Implications

    Physiological Overview

    References

    Chapter 144. CCK

    Introduction

    CCK as a Gut Peptide

    Feeding Inhibitory Actions of Peripheral CCK

    Feeding Inhibitory Actions of Endogenous CCK

    Sites of Action for Peripheral CCK in Satiety

    CCK-Induced Control of Vagal Afferent Gene Expression

    Functional Responses to Peripheral CCK in Differing Metabolic States

    Summary

    References

    Chapter 145. CRH

    Introduction

    Brain Distribution of CRH, Urocortins, and CRH Receptor

    CRH, Urocortins, and Energy Balance Regulation

    CRH and Stress-Induced Anorexia

    CRH and Stress-Induced Obesity

    Conclusions

    References

    Chapter 146. Enterostatin

    The Discovery of Enterostatin

    Chemistry of Enterostatin and Tissue Distribution

    The Receptor for Enterostatin

    Mechanism of Enterostatin in the Regulation of Food Intake and Body Weight Regulation

    Effects of Enterostatin Other than Feeding Effects

    Acknowledgments

    References

    Chapter 147. Galanin

    Introduction

    Effects of Galanin Injection on Ingestive Behavior

    Genetic Manipulation of Galanin

    Effects of Ingestive Behavior on Galanin

    Role of Galanin Receptors

    Effects of Hormones on Galanin

    Interactions Between Galanin and Other Orexigenic Transmitters

    Close Relationship Between Galanin and Circulating Lipids

    Role of Inflammation in Increased Galanin

    Clinical Support

    Summary and Conclusions

    Acknowledgments

    References

    Chapter 148. Ghrelin

    Ghrelin Regulates Feeding Behavior Across Species

    The Growth Hormone SECRETAGOG Receptor GHSR-1a Mediates Ghrelin-Induced Food Intake

    Ghrelin Targets the Hypothalamus to Regulate Feeding

    Ghrelin Targets Intracellular Fuel-Sensing Pathways in Hypothalamic Neurons to Control Feeding

    Ghrelin Targets Extra-Hypothalamic Areas to Regulate Feeding

    Ghrelin Targets Visceral Afferents to Regulate Feeding

    Peripheral Ghrelin Levels are Regulated by Feeding and Nutritional Status

    References

    Chapter 149. GLP-1

    General

    Peripheral GLP-1

    Endogenous Peripheral GLP-1

    Central Nervous System GLP-1

    GLP-1 in Obesity Therapy

    Conclusions and Perspectives

    References

    Chapter 150. Glucagon

    Introduction

    Glucagon and the Glucagon Receptor

    Glucagon Secretion

    Physiological Effects

    Pathophysiology

    Therapeutic Use

    References

    Chapter 151. Insulin

    Introduction

    Glucoregulatory Actions of Insulin

    Insulin Actions

    Insulin Secretion

    Insulin and the Brain

    Insulin and the ARC

    Interaction of Brain Insulin with Gut Hormones

    Pathophysiologic Implications of Brain Insulin Dysfunction

    Conclusions

    ACKNOWLEDGMENTS

    References

    Chapter 152. Leptin

    Leptin and Feeding Behavior

    The Absence of Leptin Action

    Leptin production and the Control of Circulating Leptin

    Leptin Receptors

    Sites of Leptin Action

    LEPR-B Signaling Pathways and the Control of Energy Balance

    “Leptin Resistance” and Cellular Mechanisms That Impair LEPR-B Signaling

    References

    Chapter 153. Melanocortins

    The Melanocortin System

    Ingestive Behavior in Humans with Mutations in the MC System

    Ingestive Behavior in Rodent Models with Disruption of MC4R Function

    Ingestive Behavior in Rodent Models with Disruption of MC3R Function

    Ingestive Behavior in Rodent Models with Disruption of AGRP Function

    Ingestive Behavior in Rodent Models with Disruption of POMC Function

    Pharmacological Studies with MCR Ligands Modulating Ingestive Behavior

    Brain Sites where MC Receptor Signaling Affects Ingestive Behavior

    Concluding Remarks

    References

    Chapter 154. NPY

    NPY and the Central Regulation of Food Intake

    Neuropeptide Y and Feeding

    NPY in the ARC Nucleus

    Peripheral Signaling Involved in the Regulation of Food Intake in the ARC

    NPY Receptors in the ARC

    The Role of NPY in the DMN

    NPY Action in the PVN

    NPY actions in VMN

    NPY action in the LHA

    NPY and Feeding Behavior

    Insight from Genetic ModelS

    Regulation of NPY Receptors in Feeding Behavior

    Conclusions

    References

    Chapter 155. Opioids

    Effects of Opioids on Feeding Behavior

    Studies from Genetic Manipulations or Mutations

    Functional Response of Opioids to Metabolic and Feeding States

    Opioid Ligands and Receptors: Sites of Action and Neural Networks Affected

    Interactions with Other Neurochemical Systems

    Physiological and Pathophysiological Implications

    Conclusions

    References

    Chapter 156. Orexin

    Introduction

    Orexin

    Lateral Hypothalamus

    Mesolimbic System

    Orexin and Mesolimbic System

    Orexin Targets

    Orexin and the Paraventricular Thalamic Nucleus

    OREXIN AND Metabolic Status

    Orexin Regulation by Feeding Peptides

    References

    Chapter 157. PYY

    Discovery

    Structure of the mRNA/Gene

    Receptors

    Regulation of PYY Secretion

    Biological Actions of PYY

    Pathophysiological Implications

    PYY Levels after Gastric Bypass surgery

    Acknowledgments

    References

    Section XIII: Gastrointestinal Peptides

    Chapter 158. Adrenomedullin

    Discovery

    Structure of the mRNA/Gene

    Processing of the Precursor

    Distribution of the mRNA/Peptide

    Receptors and Signaling Cascades

    Biological Actions Within the Gastrointestinal Tract

    Pathological Implications

    Acknowledgments

    References

    Chapter 159. Angiogenic Growth Factors

    Introduction

    Angiogenesis in Chronic GI Ulcer Development and Healing

    Angiogenic Growth Factors and GI Ulcer Healing

    Summary

    References

    Chapter 160. Apelin

    Discovery

    Structure of the Apelin mRNA/Gene, Precursor Processing

    Apelin Distribution

    Signaling Cascades

    GI and Pancreatic Actions of Apelin

    Pathophysiological Implications

    References

    Chapter 161. Bombesin-Related Peptides

    Discovery (Bn Peptides and Their Receptors)

    Structure of the mRNA/Gene

    Processing of the Precursor

    Distribution of the RNA/Peptide

    Receptors and Their Signal Cascades

    Biological Actions of Bn Peptides within the Gastrointestinal (GI) Tract

    Pathophysiological Implications of Bn Peptides within the Gastrointestinal (GI) Tract

    Pathophysiological Implications of Bn Peptides in Gastrointestinal and Other Cancers

    Possible Treatments Directed at Bn Peptides and/or Their Receptors Growth Effects on Tumors

    Possible Use of Bn Receptor Overexpression/Ectopic Expression by Tumors for Imaging/Tumor Localization

    Possible Use of Bn Receptor Overexpression/Ectopic Expression by Tumors for Molecular Targeting of Cytotoxic Agents

    Serum Levels of Bn Peptides as Tumor Markers

    Other Possible Bn Peptide Pathophysiological Implications in Nonneoplastic Diseases

    Acknowledgments

    References

    Chapter 162. CCK

    History

    Acknowledgments

    References

    Chapter 163. CGRP

    Discovery and Structure of mRNA Gene

    Distribution of mRNA/Peptide and Receptors

    Biological Actions within Gastrointestinal Tract

    Pathophysiological Implications

    Acknowledgments

    References

    Chapter 164. Galanin

    Discovery

    Structure of the Gene and Processing of the Precursor

    Distributions of Galanin

    Receptors and Signaling Cascades

    Biological Actions within the Gastrointestinal Tract

    Pathophysiological Implications

    References

    Chapter 165. Gastrin

    Discovery

    Structure of the Gene/mRNA

    Processing of the Precursor

    Distribution of the mRNA/Peptide

    Receptors and Signaling Cascades

    Biological Actions within the Gastrointestinal Tract

    Pathophysiological Implications

    Acknowledgments

    References

    Chapter 166. GIP

    Discovery

    Structure of the mRNA/Gene

    Processing of the Precursor

    Distribution of the mRNA/Peptide

    Receptors and Signaling Cascades

    Biological Actions within the Gastrointestinal Tract

    Pathophysiological Implications

    References

    Chapter 167. Ghrelin

    Discovery

    Structure of the Gene/mRNA/Peptide

    Distribution of the mRNA/Peptide

    Receptors and Signaling Cascades

    Biological Actions within Gastrointestinal Tract

    Pathophysiological Implications

    Therapeutic Potential

    References

    Chapter 168. GLP 1/2, Enteroglucagon, Glicentin, and Oxyntomodulin

    Discovery, Structure of the Gene, and Processing of the Precursor

    Expression of the Gene/Distribution of the Gene/Secretion

    Active Conformation and Metabolism

    Receptor Expression

    Biological Actions

    Actions of GLP-1

    Actions of GLP-2

    Actions of Oxyntomodulin and Glicentin

    Pathophysiological Implications

    References

    Chapter 169. Leptin

    Introduction

    The Stomach Produces Leptin

    Gastric Leptin is a Neuroendocrine Molecule for Satiety

    Gastric Leptin Enters the Intestine

    Leptin Regulates Intestinal Endocrine Secretions

    Gut Leptin and Intestinal Absorption of Nutrients

    Leptin and Gut Pathologies

    Conclusions

    Acknowledgments

    References

    Chapter 170. Motilin

    Discovery of Motilin

    Structure of Motilin and Related Peptides

    Gene structure and posttranslational processing

    Distribution in the GI Tract

    Receptor and Structure Activity

    Biological Actions

    Pathophysiological Implication

    References

    Chapter 171. Neurotensin

    Discovery

    Structure of the mRNA/Gene

    Processing of the Precursor

    Distribution of the Peptide

    Receptors and Signaling Cascades

    Biological Actions Within the Gastrointestinal Tract

    Pathophysiological Implications

    Summary

    References

    Chapter 172. Nesfatin-1

    Discovery, Structure, and Processing

    Central and Peripheral Satiety Action of Nesfatin-1

    Distribution and Biological Action of Nesfatin-1 in the GI Tract

    Pathophysiological Implication

    Perspective

    References

    Chapter 173. Obestatin

    Obestatin Discovery

    Processing from the Ghrelin Gene to Obestatin

    Obestatin Distribution

    Obestatin and GPR39

    Pathophysiological Implications

    Conclusions

    Acknowledgment

    References

    Chapter 174. Opioids

    Discovery of Opioid Peptides and Receptors

    Structure of the mRNA/Gene and Processing of the Precursor

    Distribution of the mRNA/Peptide

    Receptors and Signaling Cascades

    Biological Actions Within the Gastrointestinal Tract

    Pathophysiological Implications

    References

    Chapter 175. PACAP

    Introduction

    Cloning and Characterization of PAC1

    Receptor Binding and Intracellular Signaling Characteristics of PAC1

    Role of PACAP in the Gastrointestinal Tract

    Role of PACAP in Thermogenesis, Obesity, and Appetite

    Role of PACAP in the Immune System

    Conclusions

    References

    Chapter 176. Pancreatic Polypeptide

    Discovery

    Structure of the Gene and Protein

    Processing of PreproPP and PP

    Distribution and Secretion of PP

    Receptors and Signaling Cascades

    Biological Actions

    Pathophysiological Implications

    References

    Chapter 177. Paneth Cell α-Defensins

    Discovery of Paneth Cell α-defensins

    Defensin Gene and Precursor Structures

    Acknowledgments

    References

    Chapter 178. PYY

    Discovery

    Structure of Gene

    Processing of the Precursor

    Distribution in the Gastrointestinal Tract

    Regulation of Secretion

    Receptors and Signaling Cascades

    Biological Actions within Gastrointestinal Tract

    Pathophysiological Implications

    References

    Chapter 179. Secretin

    Discovery

    Structure of the mRNA/Gene

    Processing of the Precursor

    Distribution of the mRNA/Peptide

    Receptors and Signaling Cascades

    Biological Actions within the Gastrointestinal Tract

    Pathophysiological Implications

    Acknowledgments

    References

    Chapter 180. Somatostatin

    Discovery

    Structure of the mRNA/Gene

    Processing of the Precursor

    Distribution and Release

    Receptors and Signaling Cascades

    Biological Actions Within the Gastrointestinal Tract

    Pathophysiological Implications

    Acknowledgments

    References

    Chapter 181. Tachykinins

    Discovery of Tachykinins in the Gut

    Distribution of Tachykinin mRNAs and Peptides in the GI Tract

    Tachykinin Receptor Subtypes, Signaling, and Distribution in the GI Tract

    Biological Actions of Tachykinins in the Gut

    Pathophysiological Implications of Tachykinins in the GI Tract

    Acknowledgments

    References

    Chapter 182. TFF Peptides

    Discovery

    Structure of the mRNA/Gene

    Processing of the Precursor

    Distribution of the mRNA/Peptide

    Receptors and Signaling Cascades

    Biological Actions within the Gastrointestinal Tract

    Pathophysiological Implications

    References

    Chapter 183. Urocortins

    Discovery of Urocortins

    Urocortin Genes and Precursor Structures

    Receptors and Signaling Cascades

    Distribution of Urocortins in the GI Tract

    Biological Actions within the Gastrointestinal Tract

    Pathophysiological Implications

    Acknowledgments

    References

    Chapter 184. VIP

    Discovery

    Structure of the Gene and Processing of the Precursor

    Distribution in the Gastrointestinal Tract

    Receptors and their Signaling Pathways

    Biological Action Within the Gastrointestinal Tract

    Pathophysiological Implications

    Acknowledgments

    References

    Section XIV: Cardiovascular Peptides

    Chapter 185. Adrenomedullin Peptides

    Discovery and the Peptide Sequence of AM and Related Peptides

    Structure of the mRNA/Gene and Processing of the Precursor

    Distribution of the mRNA/Peptide and AM Circulating in the Blood Stream

    Receptor and Signaling Cascades

    Biological Actions Within the Cardiovascular System

    Pathophysiological Implications

    References

    Chapter 186. Angiotensin II Peptides

    Discovery

    Structure of the Peptides and Component of RAS

    Distribution of RAS, Processing, and Endogenous Form in the Cardiovascular System

    Receptors and their Distribution in the Cardiovascular System

    Biological Actions and Pathophysiological Implication in the Cardiovascular System

    References

    Chapter 187. Apelin

    The Apelin–APJ System

    Distribution within the Cardiovascular System

    Signaling Cascades

    Biological Actions in the Cardiovascular System

    Pathophysiological Implications

    Perspective

    Acknowledgments

    References

    Chapter 188. Bradykinin Peptides

    Discovery

    Structure of Kininogen mRNA and Gene

    Processing of the Precursor

    Distribution of Kininogen and Kallikrein mRNA, and Kinin Peptides

    Receptors and Signaling Cascades

    Biological Actions Within the Cardiovascular System

    Pathophysiological Implications

    Acknowledgments

    References

    Chapter 189. CGRP

    Discovery

    Distribution of the mRNA/Peptide in the Cardiovascular System

    Receptors and Signaling Cascades

    Biological Actions Within the Cardiovascular System

    Pathophysiological Implications

    References

    Chapter 190. Endothelins

    Discovery

    Structure of the mRNA/Gene

    Processing of the Precursor

    Distribution of the mRNA/Peptide in the Cardiovascular System

    Receptors and Their Distribution

    Biological Actions within the Cardiovascular System

    Pathophysiological Implications

    References

    Chapter 191. Ghrelin

    Introduction

    Discovery

    Structure of the mRNA/Gene

    Processing of the Precursor

    Regulation of Plasma Ghrelin Concentration

    Distribution of the mRNA/Peptide in the Cardiovascular System

    Receptors and Signaling Cascades

    Biological Actions within the Cardiovascular System

    Pathophysiological Implications

    Conclusions

    References

    Chapter 192. Natriuretic Peptides

    Discovery of Natriuretic Peptides (NPs)

    Structure of the NP mRNAs/Genes

    Processing of the NP Precursors

    Distribution of the NP mRNA/Peptide in the Cardiovascular System

    NP Receptors and Signaling Cascades

    Biological Actions of NPs in the Cardiovascular System

    Pathophysiological Implications of NPs

    References

    Chapter 193. Salusins

    Discovery

    Structure of the mRNA/Gene

    Processing of the Precursor

    Distribution of the mRNA/Peptide in the Cardiovascular System

    Receptors and Signaling Cascades

    Biological Actions within the Cardiovascular System

    Pathophysiological Implications

    References

    Chapter 194. Urocortins

    Discovery

    Structure of Urocortins mRNA/Gene

    Processing of Precursor Peptides

    Distribution of Urocortins mRNA and Peptide in the Cardiovascular System

    Receptors and Signaling Cascades

    Biological Actions Within the Cardiovascular System

    Pathophysiological and Therapeutic Implications

    Acknowledgments

    References

    Chapter 195. Urotensin Peptides

    Discovery

    Distribution of the mRNA/Peptide in the Cardiovascular System

    Receptors and Signaling Cascades

    Biological Actions within the Cardiovascular System

    Pathophysiological Implications

    References

    Chapter 196. VIP

    Introduction

    Discovery

    Distribution

    Processing

    Receptors

    Biological Actions

    Pathophysiology

    Acknowledgments

    References

    Chapter 197. VP/OT

    Discovery

    Peptide Structure

    Biological Activity

    Receptors

    Pathophysiological Implications in the Cardiovascular System

    OT and AVP in Cardiomyogenesis

    References

    Section XV: Renal Peptides

    Chapter 198. Adrenomedullin 2/Intermedin

    Discovery

    Structure of the Precursor mRNA and Gene

    Distribution of mRNA

    Processing of Precursor

    Receptors and Signaling Cascade

    Biological Actions

    Pathophysiological Implications

    References

    Chapter 199. ANP

    Discovery of Atrial Natriuretic Peptide Actions in the Kidney

    Effects of ANP on Tubular Transport Systems

    References

    Chapter 200. Endothelin

    Basic Components of the Endothelin System

    Localization of the ET-1 System in the Kidney

    Renal Hemodynamic Effects of ET-1

    ET-1 Control of Excretory Function

    Renal ET-1 in Hypertension

    ET and Kidney Disease

    Conclusions

    References

    Chapter 201. Neurohypophyseal Peptides

    Brief History and Overview of the Neurohypophyseal Peptides

    Body Fluid Homeostasis

    Vasopressin and Oxytocin Receptors

    Localization of Vasopressin and Oxytocin Receptors in the Kidney

    Renal Effects of Vasopressin

    Renal Effects of Oxytocin

    References

    Chapter 202. Peptides, Sex, Diabetes, and the Kidney

    Introduction

    Etiology of Diabetic Nephropathy

    Peptide Regulation of Renal Function in the Diabetic Kidney

    Estrogen–Peptide Interactions in the Diabetic Kidney

    Androgen–Peptide Interactions in the Diabetic Kidney

    Summary and Perspectives

    Acknowledgments

    References

    Chapter 203. Prolactin

    Classical production site and actions of prolactin

    Prolactin Receptors

    Prolactin and Osmoregulation

    Prolactin Receptors in the Mammalian Kidney

    Renal Production of Prolactin

    Renal Actions of Prolactin

    The Jury is Still Out on the Renal Actions of Prolactin

    Have Transgene Methods Clarified the Issue?

    References

    Chapter 204. Renin–Angiotensin System

    Introduction

    Distribution of Angiotensinogen, Renin, (Pro)renin Receptors, Angiotensin Converting Enzymes, and Ang Type 1 Receptors in the Kidney

    Intrarenal Levels of Angiotensin II

    Biological Actions of Intrarenal Ang II

    Concluding Comments and Perspective

    Acknowledgments

    References

    Section XVI: Respiratory Peptides

    Chapter 205. Adrenomedullin

    Introduction

    AM Expression and Clearance in the Lung

    AM in Models of Acute Lung Inflammation

    AM and Pulmonary Arterial Hypertension

    AM and Chronic Lung Disease

    AM—Mode of Action in the Lung

    Conclusions

    References

    Chapter 206. Endothelin-1

    Introduction

    Endothelin Genes, Cellular Distribution, Synthesis, Receptors, and Regulation

    Airway Diseases

    Pulmonary Vascular Disease

    Lung Transplantation and Rejection

    Pulmonary Malignancies

    Acute respiratory Distress Syndrome (ARDS)

    Pulmonary Fibrosis

    Conclusions

    References

    Chapter 207. Kinin Receptors

    Introduction

    Kinins

    Kinin Receptors

    Kinin Receptors Expression

    Role of Kinin Receptors in Airways

    Contribution of Immune Cells to Airway Inflammation Induced by Kinin Receptors

    Kinin Receptors in Lung Fibrosis and Airway Tissue Remodeling

    Kinin Receptors in Lung Inflammation Induced by Cigarette Smoke Exposure

    Conclusions

    Acknowledgments

    References

    Chapter 208. PACAP

    Discovery, Structure, and Synthesis of PACAP

    PACAP Receptors and Signaling

    Biological Actions and Pathological Implications

    Conclusions

    References

    Chapter 209. VIP

    How Was VIP Discovered?

    VIP Is a Member of a Family of Peptides

    Tissue Distribution and Cellular Localization

    Colocalization with Other Peptides and Neurotransmitters

    Biological Actions in the Lung

    Receptors and Signal Transduction Pathways

    Physiological Roles

    VIP in the Pathogenesis and Modulation of Pulmonary Disease

    Cystic Fibrosis (CF)

    References

    Section XVII: Opiate Peptides

    Chapter 210. Antiopioid Peptides

    Introduction

    Regulation of Opioid Analgesia by CCK

    CCK Gene Expression in Response to Opioid Analgesia

    The Role of CCK in the Development and Maintenance of Chronic Pain

    CCK Release in Response to Opioid Analgesia

    CCK–Opioid Interactions in Physiological Functions Other than Pain

    Cellular and Molecular Mechanisms for CCK–Opioid Interactions

    CCK as Mediator of Other Peptides with ANTIOPIOID Effect

    Regulation of Opioid Analgesia by NPFF

    Regulation of Opioid Analgesia by Nociceptin/Orphanin FQ

    Regulation of µ-Opioid Systems by MIF-1, TYR-MIF-1, and TYR-W-MIF-1

    Conclusions

    Acknowledgments

    References

    Chapter 211. Casomorphins/Hemorphins

    Introduction

    Discovery of the β-Casomorphins and the Hemorphins

    The Formation of β-Casomorphins and Hemorphins

    Receptor Selectivity and Its Modulation

    Biological Actions and Functional Relevance of the β-Casomorphins and Hemorphins

    Implication of β-Casomorphins and Hemorphins in Pathophysiolgy

    Concluding Remarks

    Acknowledgments

    References

    Chapter 212. Endomorphins

    Discovery of Endomorphins

    Distribution of the Endomorphins in the Central Nervous System

    Receptor Selectivity and Its Modulation

    Biological Actions of Endomorphins

    Pathophysiological Implications of Endomorphins

    Concluding Remarks

    Acknowledgments

    References

    Chapter 213. Evolution of the Opioid System

    Peptide Family

    Receptors

    Evolution Of The Opioid System

    Concluding Remarks

    References

    Chapter 214. Exorphins

    Opioid Peptides Derived from Plant Proteins

    Opioid Peptides Derived from Animal Proteins (see the Hemorphins/Casomorphins Chapter in This Section of the Book)

    Intraprotein Opioid Sequence

    Classification of Exorphins According to Their Structure

    Opioid Antagonist and Antiopioid Peptide Derived from Proteins

    Concluding Remarks

    References

    Chapter 215. Nociceptin/Orphanin FQ

    The Discovery of Nociceptin/Orphanin FQ

    The N/OFQ Peptide

    The NOP Receptor

    Pharmacological and Genetic Tools

    Biological Actions

    Therapeutic Potential of NOP Receptor Ligands

    References

    Chapter 216. Opioid-Substance P Chimeric Peptides

    Introduction

    CrossInteraction of Tachykinin and Opioid Systems

    Tachykinin Antagonist–Opioid Agonist Chimeric Compounds

    Tachykinin Agonist–Opioid Agonist Chimeric Compounds

    Conclusions

    References

    Chapter 217. POMC-Derived Opioid Peptides

    History

    Structure of β-Endorphin

    Location and Mechanism of Action

    Function

    β-Endorphin and Mu Receptor Functions

    β-Endorphin and Obesity

    β-Endorphin as a Neuromodulator of the Cardiovascular System

    β-Endorphin and the Immune System

    Miscellaneous Roles of β-Endorphin

    Summary

    References

    Chapter 218. Prodynorphin-Derived Peptides

    Discovery

    Structure of the Precursor mrna/Gene

    Processing

    Receptors

    Conformational Analysis of Dyn A(1–17)

    Dynorphin Expression in the Central Nervous System and Possible Biological Actions

    Pathophysiological Implications

    Drug Abuse and Dynorphins

    Dynorphin Expression in Peripheral Tissues

    Perspective

    References

    Chapter 219. Proenkephalin-Derived Peptides

    Discovery of the Enkephalins

    Structure of the Precursor Gene

    Distribution of Enkephalin mrna and Peptide

    Processing

    Receptors

    Biological Activity of Enkephalins

    Pathophysiological Implications

    Clinical Studies With Ogf

    References

    Section XVIII: Neurotrophic Peptides

    Chapter 220. Activity-Dependent Neuroprotective Protein (ADNP) and Davunetide (NAP)

    Discovery and Structure of ADNP and Davunetide (NAP)

    The ADNP Gene

    ADNP Expression

    ADNP Interacting Proteins

    ADNP Biological Actions

    The ADNP-Derived Neuroprotective Peptide NAP: Biological Actions and Microtubule Connection

    Cytoskeleton Protection, In Vitro

    Cytoskeleton Protection, In Vivo

    Broad Neuroprotective Scope

    General Consideration for Microtubule Protection

    Clinical Progress

    Working Hypothesis and Future Perspectives

    Conflict of Interest

    Acknowledgments

    References

    Chapter 221. Erythropoietin

    Discovery and Structure of Epo

    The Epo Gene

    Distribution of Epo and Epo mRNA

    Processing of Epo

    The Epo Receptor

    Epo Biological Actions

    Pathophysiological Implications

    References

    Chapter 222. Insulin-like Growth Factor-1

    Discovery

    Structure of Precursor mrna/Gene

    Distribution of the mrna

    Processing

    Receptors

    Active and/or Solution Conformation

    Biological Actions

    Pathophysiological Implications

    Conclusions and Future Directions

    References

    Chapter 223. Neuregulins

    Discovery and Structure

    Distribution and Processing

    Receptors

    Biological Actions

    ACKNOWLEDGMENTS

    References

    Chapter 224. Neurotrophins

    Discovery of Nerve Growth Factor

    Structure of the mRNA/Gene

    Distribution of the mRNA

    Conformation

    Receptors—Binding Sites

    TrkA and p75 Receptors—Structure

    Trk Receptor Signaling

    p75 Receptor Signaling

    Neurotrophins—Retrograde Transport

    Neurotrophins—Physiological Role and Roles in Pathology

    Clinical Prospects

    References

    Chapter 225. TGF-β

    Discovery

    Structure of the RNA/Gene

    Processing of the Precursor

    Receptors and Signaling Cascades

    Distribution of the mRNA/Peptide

    Biological Actions

    Pathophysiological Implications of TGF-β

    Summary

    Acknowledgments

    References

    Section XIX: Blood–Brain Peptides

    Chapter 226. Augurin and Ecrg4-derived Neuropeptides

    Introduction

    Discovery of Preponderant Expression of Augurin in Choroid Plexus

    Exploring Physiologic Roles for Augurin

    CSF as a Circulatory Link between CP and Brain

    Peptide Traffic through the Blood–CSF Barrier vs. Blood–Brain Barrier

    CSF-Peptide-mediated Homeostatic Responses in CNS Pathophysiology

    Elements of an Injury Response Feedback Loop

    Level of Augurin Peptide Expression and Degree of NPC Mitosis in TBI

    Titrating SVZ Proliferation by Altering Augurin in the CP–CSF–Ependymal Nexus

    Augurin Release: Relation to Autocrine vs. Endocrine Homeostatic Mechanisms

    Conclusions

    References

    Chapter 227. Diseases Mediated by the BBB: Alzheimer’s, Obesity, and Beyond

    Introduction

    Leptin and Obesity

    Amyloid β Protein Efflux and Alzheimer’s Disease

    Methionine Enkephalin and Alcohol Withdrawal

    GLUT-1 Deficiency Syndrome

    Insulin Resistance in Sepsis

    Summary

    References

    Chapter 228. Hypothalamic Neuropeptides

    Introduction

    TRH

    GnRH

    Corticotropin-Releasing Hormone (CRH)

    Vasopressin (antidiuretic hormone)

    Oxytocin

    Somatostatin

    PACAP

    References

    Chapter 229. Ingestive Peptides

    Introduction

    Insulin

    Leptin

    Ghrelin

    Other Ingestive Peptides and Proteins: Special Interactions with the BBB

    Actions Other than Feeding

    Summary

    References

    Chapter 230. Neurotrophic Peptides

    Introduction

    Resolution of Myths about Peptides and their CNS Effects: In Vivo and In Vitro Methodologies

    Binding Proteins that Affect the Stability and Permeation Kinetics: Intravenous Delivery vs In Situ Brain Perfusion

    Presence of Receptors at the Apical or Basolateral Surface of the BBB: Useful or Not for Peptide Transport?

    Adsorptive Endocytosis and Chemical Modifications that Enhance Delivery across the BBB

    The Intracellular Trafficking of Peptides that Leads to Exocytosis

    Specific Examples of the Pharmacokinetics of BBB Permeation

    The Situation of the Partially Disrupted BBB and Selective Regulation of the Transport System in Pathophysiology

    Enhanced Delivery of Neurotrophic Peptides: How it Affects Neuroregeneration

    Summary

    References

    Chapter 231. Oligopeptide and Peptide-Like Drug Transport

    Introduction

    Blood–Brain Barriers: General Properties

    Oligopeptide Transport at the BBB

    Peptidases at the BBB

    Oligopeptide Transporters at the Choroid Plexus

    Peptidases at the Choroid Plexus

    Peptide and Peptide-Like Drug Transport at the BCSFB

    Regulation of Peptide Transport

    Summary

    Acknowledgments

    References

    Chapter 232. Opioid Peptides

    Introduction

    Stability

    Transport

    BBB and Disease, Will It Change Opioid Peptide Delivery?

    Conclusions

    References

    Chapter 233. Peptide Delivery

    Introduction

    Models to Study Brain Delivery of Peptides

    Methods to Improve Paracellular Peptide Delivery Through the BBB

    Formation of Cyclic Peptides to Improve Transcellular Delivery Through the BBB

    Improving Enzymatic Stability

    Targeting Saturable Transport Systems in the BBB to Improve Delivery into the CNS

    Use of Receptor-Mediated Drug Transport to Improve Peptide Delivery into the Brain

    Conclusions

    Acknowledgments

    References

    Section XX: Peptide Biosynthesis/Processing

    Chapter 234. Acetylation

    Acetylation of Bioactive Peptides

    Acetyl Transferases

    Distribution and Localization of Peptide Acetyl Transferase Activity

    Pathophysiology of Acetylated and Nonacetylated α-MSH and β-Endorphin

    Conclusions

    References

    Chapter 235. Carboxypeptidases E and D

    Name and History

    Function in Peptide Biosynthesis

    General Properties

    Substrate Specificity and Regulation of Activity

    Distribution/Localization

    Pathophysiological Implications

    Later Findings

    References

    Chapter 236. Disulfide Bond Formation

    Introduction

    The Concept of Secretory Pathway Catalysis of Disulfide Bond Formation

    Transfer of Reducing Equivalents from the ER Lumen to the Cytosol

    Proper Disulfide Bond Formation in the Secretory Pathway may also Include Disulfide Reduction and Isomerization

    The Family of PDI-like ER Oxidoreductases

    Selective Activities of Oxidoreductases within the ER Environment

    Oxidation of Specific Bioactive Peptide Substrates within the ER: the Case of Proinsulin

    Conclusions

    References

    Chapter 237. Ghrelin O-Acyltransferase (GOAT)

    Introduction

    Name and History of GOAT

    Functions of GOAT in Ghrelin Processing

    Properties

    Stimulation of GOAT

    Substrate Specificity of GOAT

    Regulation of Activity

    Pathophysiological Implications

    References

    Chapter 238. Glutaminyl Cyclases

    N-Terminal pGlu-Modification of Peptides and Proteins

    Glutaminyl Cyclases

    References

    Chapter 239. In Silico Search for Biologically Active Peptides

    Background of GPCR Deorphanization

    Prediction of Bioactive Peptides: Biosynthetic Pathway of Bioactive Peptides and the Empirical Cleavage Rules

    Prediction of Bioactive Peptide Candidates

    Perspectives

    References

    Chapter 240. New Mass Spectrometric Approaches for Uncovering Neuropeptides

    Introduction

    MS-Based Neuropeptide Discovery

    Conclusions

    Acknowledgments

    References

    Chapter 241. Peptide Degradation (Neprilysin and Other Regulatory Peptidases)

    Introduction

    Neutral Endopeptidase (Neprilysin) Family

    The ACE Family (ACE and ACE-2)

    Insulin-Degrading Enzyme (Insulysin, IDE)

    Proline-Directed Peptidases

    Conclusions

    References

    Chapter 242. Peptidomics of Mice Lacking Peptide Processing Enzymes

    Introduction

    Quantitative Peptidomic Techniques

    CPE-deficient Mice

    PC Knockout Mice

    Conclusions

    References

    Chapter 243. Peptidomics Strategy for Discovering Endogenous Biologically Active Peptides

    Mass Spectrometry in Endogenous Peptide Research

    Peptidomic Identification and Biological Validation of Novel C-Terminally Amidated Peptides: Neuroendocrine Regulatory Peptides (NERPs)

    Elucidating Precursor Cleavage Sites by Secretopeptidome Analysis

    A Universal Peptidomics Strategy for Discovering Endogenous Biologically Active Peptides

    Focused Secretopeptidome Mining: Discovery of Antimicrobial Peptide AMP-IBP5

    Conclusions

    Acknowledgments

    References

    Chapter 244. Peptidylglycine Amidating Monoxygenase (PAM)

    Name and History

    Function of PAM in Peptide Biosynthesis

    Properties of the PHM Domain of PAM

    Properties of the PAL Domain of PAM

    The PAM Gene

    Regulation of PAM Activity

    Distribution/Localization: Biosynthetic and Endocytic Trafficking of PAM

    Inhibitors of Amidation

    Pathophysiological Implications

    Later Findings

    References

    Chapter 245. Prohormone Convertase 1/3

    Discovery and General Features of PC1/3

    Peptide Biosynthesis and Processing: PC1/3 Function

    Properties of PC1/3

    Distribution/Localization

    Pathophysiological Implications of PC1/3 Variants

    Summary and Conclusions

    References

    Chapter 246. Prohormone Convertase 2

    Discovery and General Features Of PC2

    PC2 Function in Peptide Biosynthesis and Processing

    Properties Of PC2

    Distribution/Localization Of PC2

    Pathophysiological Implications of PC2 and 7B2 Variants and Null Animals

    Summary and Conclusions

    References

    Chapter 247. Proprotein Convertase Furin and Proprotein Convertase PC5/6

    Discovery and Nomenclature

    Functions in Peptide Biosynthesis/Processing

    Conclusions

    Acknowledgments

    References

    Chapter 248. Proprotein Convertases PC4, PACE4, and PC7

    Discovery and Nomenclature

    Functions in Polypeptide Biosynthesis/Processing

    Conclusions

    Acknowledgments

    References

    Chapter 249. Proprotein Convertases SKI-1/S1P and PCSK9

    Discovery and Nomenclature

    Functions in Polypeptide Biosynthesis/Processing

    Conclusions

    Acknowledgments

    References

    Chapter 250. Tyrosylprotein sulfotransferases

    Function in Cellular Synthesis and Processing of Peptides

    Enzyme Properties

    Distribution

    Patophysiological Implications

    Immunochemical and Diagnostic Implications

    Additional Findings

    References

    Section XXI: General Peptide Topics

    Chapter 251. Classical Neurotransmitters and Neuropeptides

    Some Historical Notes on Neurotransmitters

    Neuropeptide Research—The Beginnings

    Neuropeptides at Karolinska

    Neurotransmitter Storage—Synaptic Versus Dense Core Vesicles

    Neurotransmitter Coexistence

    Plasticity in Neuropeptide Expression

    Neuropeptide Receptors

    Neuropeptide Receptors and Drug Development

    Concluding Remarks

    Acknowledgments

    References

    Chapter 252. Evolution in Action: Skin Peptides

    Introduction

    Agnatha

    Elasmobranchii

    Teleostei

    Amphibia

    Conclusions

    References

    Chapter 253. Peptide Chronomics

    Preamble

    Introduction

    Avoiding Blunders

    Chronomics Spawned by Chronobiology Maps Dynamics

    Endpoints

    Susceptibility Rhythms

    Atlas

    Beginnings of Opportunistic Mapping along the Scale of Years

    Chronomics in Men

    Chronomics in Women

    Discussion

    Acknowledgments

    References

    Chapter 254. Peptides and Behavior

    Introduction

    General Features of Peptide Modulation of Behavior

    Peptide Modulation of Specific Behaviors

    Consummatory Behavior

    Peptide Therapeutics

    Conclusion

    References

    Chapter 255. Peptides and Sleep

    Introduction

    Hypothalamic–Pituitary–Somatotropic (HPS) System

    Hypothalamic Pituitary Adrenocortical System

    Corticotropin

    Hypothalamic–Pituitary–Thyroid System

    Other Peptides

    Orexins/Hypocretins

    Conclusions

    Acknowledgments

    References

    Chapter 256. Peptides and Stress

    Introduction

    The “Stress” Concept

    CRH

    Neuropeptide Y

    Evidence for Interactions between CRH and NPY Systems

    Urocortins

    Substance P

    Neuropeptide S

    Arginine Vasopressin

    Concluding Remarks

    Chapter 257. Peptides and Temperature

    Introduction

    Body Temperature and Its Regulation

    Participants of Energy Balance Regulation

    Acknowledgment

    References

    Chapter 258. Pheromone Peptides

    Introduction

    Bacterial Pheromone Peptides

    Fungal Pheromone Peptides

    Ciliates

    Mollusk Pheromone Peptides

    Annelid Pheromone Peptides

    Arthropod Pheromone Peptides

    Vertebrate Pheromone Peptides

    Summary

    References

    Chapter 259. Prebiotic Peptides

    Introduction

    The Primitive Earth Scenario

    The Formation of Amino Acids

    The Formation of Peptides

    A ‘Peptide World’ as the Origin of Life?

    References

    Chapter 260. Viral Fusion Peptides

    Introduction

    Methods to Analyze Fusion Peptide Structure and Function

    Fusion Peptides in Retroviruses

    Fusion Peptides in Paramyxoviruses

    Conclusions and Prospects

    Acknowledgments

    References

    Index

    Color Plates

Product details

  • No. of pages: 2032
  • Language: English
  • Copyright: © Academic Press 2013
  • Published: January 26, 2013
  • Imprint: Academic Press
  • eBook ISBN: 9780123850966

About the Editor

Abba Kastin

Affiliations and Expertise

Pennington Biomedical Research Center, Baton Rouge, LA, USA

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