Functional Selectivity of G Protein Coupled Receptor Ligands

by Neve, Kim A.

• ISBN13: 9781603273343
• ISBN10: 1603273344
• Edition: 1st
• Format: Hardcover
• Copyright: 2009-04-22
• Publisher: Humana Pr Inc

Summary

Functional selectivity refers to the ability of different ligands acting at one receptor subtype to activate multiple signaling pathways in unique combinations; that is, one drug can be an agonist at pathway A and an antagonist or partial agonist at pathway B, and another drug can have the reverse profile. Functional selectivity has profound implications for drug development, for chemical biology, and for the design of experiments to characterize receptor function. In Functional Selectivity of G Protein-Coupled Receptors expert neuroscientists and pharmacologists review the work that demonstrated the existence of functional selectivity, placed it within a theoretical framework, and provided a mechanistic basis for the phenomenon. This exciting, comprehensive, and future-oriented volume includes chapters that focus on theoretical and mechanistic aspects of functional selectivity and that cut across subfamilies of GPCRs. Additional chapters focus on subfamilies of therapeutically relevant receptors where there is considerable evidence of ligand functional selectivity. Accessible and authoritative, Functional Selectivity of G Protein-Coupled Receptors is a valuable educational tool and reference source for students and scientists interested in drug development, chemical biology, and GPCR function.

Table of Contents

Preface	p. v
Contributors	p. ix
Theoretical And Mechanistic Aspects Of Functional Selectivity
Historical Overview of the Concept of Functional Selectivity	p. 3
Functional Selectivity: Theoretical Considerations and Future Directions	p. 9
Agonist-Selective Coupling of G Protein-Coupled Receptors	p. 25
Ligand-Selective Receptor Desensitization and Endocytosis	p. 55
Selectivity for G Protein or Arrestin-Mediated Signaling	p. 71
In Vivo Evidence for and Consequences of Functional Selectivity	p. 87
Subfamilies Of Therapeutically Relevant Receptors
Functional Selectivity at Adrenergic Receptors	p. 107
Signaling Diversity Mediated by Muscarinic Acetylcholine Receptor Subtypes and Evidence for Functional Selectivity	p. 125
Functional Selectivity at Serotonin Receptors	p. 155
Functional Selectivity at Dopamine Receptors	p. 177
Functional Selectivity at Receptors for Cannabinoids and Other Lipids	p. 211
Functional Selectivity at Opioid Receptors	p. 243
Functional Selectivity at Non-Opioid Peptide Receptors	p. 267
Index	p. 283
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