This book is based on presentations given at CGRP '98, the Third International Meeting on CGRP and related peptides held in the UK in May 1998. The principal speakers have each contributed a chapter and many of the short and poster communications will also be found here. This book follows from the tradition set by the First and Second Meetings in 1992 and 1995 when the proceedings were published. The work is aimed at the specialist in the field, but it is hoped that many of the chapters will also prove useful as introductions to those wishing to gain greater familiarity with the biology and pharmacology of these important peptides. The book begins with a broad overview of the field, past and present. It is followed by two chapters dealing with the "classical" pharmacology of CGRP. In particular there is an account of the pitfalls of the present generation of CGRP antagonists and the dangers of assuming that every action of CGRP is mediated by a CGRP receptor. However the bulk of this section is taken up by the recent developments concerning the cloning of receptors for CGRP and adrenomedullin. An exciting story is emerging of how a single molecule, calcitonin receptor-like receptor (CRLR), can mediate the response to both CGRP and adrenomedullin depending on the presence of different members of a family of accessory proteins, the Receptor Activity Modifying Proteins (RAMPs). This is covered in three chapters and is followed by an account of another accessory protein associated with CGRP responsiveness, Receptor Component Protein (RCP). Following sections of the book deal with the biochemistry, physiology and pharmacology of receptors for the allied peptides amylin and adrenomedullin. The close connections between amylin and calcitonin receptors are highlighted and role of amylin in the regulation of food intake is then considered. The molecular nature of adrenomedullin receptors is addressed in an earlier chapter but in this section their pharmacology is examined. The pathophysiology of CGRP and related peptides formed a significant part of the meeting. Three chapters examine the role of CGRP in vascular disorders, joint dysfunction and gastrointestinal pathology. A separate section considers the role of CGRP in headache and migraine. The book concludes with a selection of the short oral and poster communications and then an important appendix, reflecting a workshop held to discuss the nomenclature of CGRP, amylin and adrenomedullin receptors. As the majority of the active workers in the field were present at this meeting it is hoped that the consensus view presented here might be widely acceptable.
Table of Contents
Section 1: Pharmacology and Molecular Biology of CGRP Receptors 1. Multiple Receptors for CGRP and Related Peptides 2. CGRP Receptor Heterogeneity: Use of CGRP8-37 3. Structure Activity Relationship for CGRP 4. The Binding of CGRP and Adrenomedullin to a Cloned Receptor 5. CGRP Receptors, Structure and Function 6. Receptor Activity Modifying Proteins(RAMPS) and CRLR Define the Receptors for CGRP and Adrenomedullin 7. The CGRP-Receptor Component Protein: A Novel Signal Transduction Protein Section 2: Amylin Receptors 8. What Makes an Amylin Receptor? 9. Neuroendocrine Actions of Amylin Section 3: Adrenomedullin Receptors 10. Characterization of Adrenomedullin Receptor Binding in Rat Tissues and Cell Lines 11. Cardiovascular Actions of Adrenomedullin Section 4: General Pathophysiology of CGRP, Amylin and Adrenomedullin 12. Calcitonin Gene-Related Peptide in Gastrointestinal Homeostasis 13. CGRP and Neurogenic Vasodilatation: Role of Nerve Growth Factor in Diabetes 14. Neurogenically-Derived Pathological Hyperaemia in Articular Tissues Section 5: CGRP in Migraine and Headache 15. Evidence of the Involvement of CGRP in Migraine and Cluster Headache: A Physiological Perspective 16. CGRP, CGRP mRNA and CGRP1 Receptor mRNA and Release from the Human Trigeminovascular System Section 6: Short Communications 17. Investigation of Different Pathways for the Relaxant Responses of Human αCGRP and βCGRP on Guinea Pig Basilar Artery 18. CGRP Receptors in Rat Intramural Left Coronary Arteries 19. Discrete Expression of a Putative CGRP Receptor (RDC1) mRNA in the Rat Brain and Peripheral Tissues 20. Amylin-Immunoreactivity in Monkey Hypothalamus 21. Analysis o f Responses to hAmylin and hCGRP in Isolated Resistance Arteries from the Mesenteric Vascular Bed of the Rat 22. Adrenomedullin in the Rat Placenta and Uterus 23. Effects of ADM and CGRP on Erectile Activity in the Cat 24. Evidence for a Specific Endothelial Cell Adrenomedullin Receptor Regulating Endothelin-1 Gene Expression and Synthesis 25. Antimicrobial Effects of Adrenomedullin and CGRP 26. The Comparative Activity of Adrenomedullin and CGRP to Potentiate Inflammatory Oedema Formation 27. The Effects of a Selective CGRP1 Receptor Antagonist, and a Selective Neuronal Nitric Oxide Synthase Inhibitor on Neurogenic Vasodilatation in the Rat 28. CGRP and NO in the Regulation of Blood Flow in Rabbit Knee Joints 29. CGRP Modulates LPS- and Cytokine-Induced iNOS/NO Formation 30. Identification and Regulation of CGRP in T Lymphocytes of the Rat 31. CGRP and Pregnancy 32. Characterization of CGRP Receptors in Human Cranial Arteries 33. CGRP-Mediated Dural Vessel Vasodilation Produces Sensitisation of Trigeminal Nucleus Caudalis Neurones in Rats 34. Mechanism of CGRP Release from Sensory Nerve Terminals in Isolated Trachea of the Rat 35. Expression and Distribution of CGRP Peptide and Receptor in Human Skin