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Agonist-Selective Coupling of G Protein-Coupled Receptors

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Functional Selectivity of G Protein-Coupled Receptor Ligands

Part of the book series: The Receptors ((REC))

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Abstract

During the last 20 years, molecular and biochemical data concerning G protein-coupled receptors (GPCRs) have accumulated, providing a detailed characterization of the structure and function of this large family of receptors. Initially viewed as simple transducing proteins interacting with intracellular adapters that confer signaling specificity and amplification, the last decade has revealed the extreme complexity and flexibility offered by these membrane receptors. Indeed, the capacity to interact with several unrelated G proteins, which was originally considered as a peculiar property of some recombinant receptors, is now demonstrated for the vast majority of GPCRs. The mechanisms governing and regulating this multiplicity of coupling have been deeply investigated, highlighting the physiological and pharmacological consequences, which are herein reviewed. Of particular importance is the emerging concept of functional selectivity, which explains the capacity of a ligand to selectively orientate the coupling of a receptor with a subset of G proteins. Obviously, future studies should help to transpose functional selective ligands into functional selective drugs showing enhanced clinical efficacy with lower unwanted side effects. In addition, ligands endowed with functional selectivity constitute relevant tools for exploring the GPCR functions in physiological and pathological processes.

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Acknowledgments

This study was supported by grants from the National Fund for Scientific Research. EH is Research Director of the F.N.R.S.

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  1. Laboratoire de Pharmacologie Expérimentale, Université catholique de Louvain, 1200, Brussels, Belgium

    Barbara Bosier & Emmanuel Hermans

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  1. Barbara Bosier
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  2. Emmanuel Hermans
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Correspondence to Emmanuel Hermans .

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  1. VA Medical Center, 3710 SW US Veterans Hospital Road, 97239-2999, Portland, OR, USA

    Kim A. Neve

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Bosier, B., Hermans, E. (2009). Agonist-Selective Coupling of G Protein-Coupled Receptors . In: Neve, K.A. (eds) Functional Selectivity of G Protein-Coupled Receptor Ligands. The Receptors. Humana Press. https://doi.org/10.1007/978-1-60327-335-0_3

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