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  • Book
    Susan D. Brain, Pierangelo Geppetti, editors.
    Summary: This book is designed to focus on the role of Calcitonin Gene-Related Peptide (CGRP) in health and disease. This peptide, originally discovered in the 1980s as a sensory neuropeptide with cardiovascular effects, is now known to play a distinct role in the pain processing of migraine. The various chapters address the origin, localization and function of CGRP and its receptor in the peripheral nervous system, in the cardiovascular system, and in other tissues and organs. Further attention is paid to the drug discovery pathway where recent findings show the beneficial effect of small molecule antagonists of the CGRP receptors for the relief of the migraine attack and of monoclonal antibodies against CGRP or the CGRP receptor for migraine prevention.

    Intro; Preface; Contents; CGRP Discovery and Timeline; 1 Discovery of the Sensory Neuropeptide Calcitonin Gene-Related Peptide; 2 Family and Structure; 3 Receptors; 4 Migraine; 5 Antagonists; 6 Antibodies; 7 Other Indications for Calcitonin Gene-Related Peptide Antagonists and Antibodies; 8 Role of Calcitonin Gene-Related Peptide in the Cardiovascular System; 9 The Therapeutic Potential of Calcitonin Gene-Related Peptide Agonists; 10 Conclusion; References; CGRP Receptor Biology: Is There More Than One Receptor?; 1 Introduction; 2 Proteins with Affinity for Calcitonin Gene-Related Peptide 2 Excitatory Receptors in Primary Sensory Neurons2.1 Receptors for ATP; 2.2 PAR Receptors; 2.3 Serotonin Receptors; 2.4 Bradykinin and Prostaglandin Receptors; 3 Excitatory Channels in Trigeminal Primary Sensory Neurons; 3.1 Sodium Channels; 3.2 TRP Channels; 4 Inhibitory Receptors and Channels in Trigeminal Primary Sensory Neurons; 4.1 Adenosine Receptors; 4.2 Serotonin 5-HT1D Receptors; 4.3 Potassium Channels; 5 Agents that Provoke Migraine Attacks and Release CGRP; 5.1 Nitric Oxide Donors; 5.2 Ethanol and TRPV1; 5.3 TRPA1 Agonists 3 Pharmacology of Calcitonin Gene-Related Peptide-Responsive Receptors4 Calcitonin Gene-Related Peptide Receptors in Migraine; References; The Structure of the CGRP and Related Receptors; 1 Introduction to the CGRP Receptors; 2 The Extracellular Domain of Calcitonin Receptor-Like Receptor/Receptor Activity-Modifying Protein 1; Peptide Binding; 3 The Extracellular Domain of Calcitonin Receptor-Like Receptor/Receptor Activity-Modifying Protein 1; Non-peptide Antagonist ... ; 4 The TM Domains of Calcitonin Receptor and Calcitonin Receptor-Like Receptor; 5 The C-Terminus 5.2 Calcitonin Gene-Related Peptide Receptor Activation of Endosomal Signalling Pathways6 Calcitonin Gene-Related Peptide-Mediated Signalling in Primary Cells; 6.1 Calcitonin Gene-Related Peptide Signalling in Neuronal Cells; 6.2 Calcitonin Gene-Related Peptide Signalling in Glial Cells; 6.3 Calcitonin Gene-Related Peptide Signalling in Vascular Smooth Muscle Cells; 7 Conclusions; References; Pathways of CGRP Release from Primary Sensory Neurons; 1 Sources of CGRP Release; 1.1 Primary Sensory Neurons; 1.2 Intrinsic Gut Neurons; 1.3 Central Neurons; 1.4 Non-neuronal Cells 6 Receptor Component Protein7 Conclusion; References; CGRP Receptor Signalling Pathways; 1 The Discovery of the Calcitonin Gene-Related Peptide Receptor; 2 Calcitonin Gene-Related Peptide Receptors Mediate G Protein-Dependent Signalling; 3 Calcitonin Gene-Related Peptide Receptor Component Protein; 4 Calcitonin Gene-Related Peptide Receptor Internalization and Trafficking; 5 Calcitonin Gene-Related Peptide Receptor Signalling Pathways in Model Cell Lines; 5.1 Activation of Calcitonin Gene-Related Peptide Receptors Promotes Activation of Protein Kinases
    Digital Access Springer 2019