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Approaches to Assess Functional Selectivity in GPCRs: Evaluating G Protein Signaling in an Endogenous Environment

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G Protein-Coupled Receptors in Drug Discovery

Part of the book series: Methods in Molecular Biology ((MIMB,volume 1335))

Abstract

Ligand-directed signaling, biased agonism, and functional selectivity are terms that describe the propensity of a ligand to drive signaling toward one GPCR pathway over another. Most of the early examples demonstrated to date examine the divergence between GPCR signaling to G protein coupling and βarrestin2 recruitment. As biased agonists begin to become available based on cell-based screening criteria, a need arises to determine if G protein signaling biases will be maintained in the endogenous setting, wherein receptors are functioning to control relevant biological responses. This report presents our method and offers tips for evaluating G protein signaling in endogenous tissues. Predominately, brain tissues are discussed here; optimization points that can be applied to any tissues are highlighted.

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Acknowledgement

NIH/NIDA grants DA0031927, DA033073, DA009158 fund G protein signaling projects in our laboratory.

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Authors and Affiliations

  1. Departments of Molecular Therapeutics and Neuroscience, The Scripps Research Institute, 130 Scripps Way #2A2, Jupiter, FL, 33458, USA

    Laura M. Bohn & Lei Zhou

  2. Kellogg School of Science and Technology, The Scripps Research Institute Graduate Studies Program, Jupiter, FL, 33458, USA

    Jo-Hao Ho

Authors
  1. Laura M. Bohn
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  2. Lei Zhou
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  3. Jo-Hao Ho
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Corresponding author

Correspondence to Laura M. Bohn .

Editor information

Editors and Affiliations

  1. Department of Structural and Chemical Biology, Icahn School of Medicine at Mount Sinai, New York, New York, USA

    Marta Filizola

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Bohn, L.M., Zhou, L., Ho, JH. (2015). Approaches to Assess Functional Selectivity in GPCRs: Evaluating G Protein Signaling in an Endogenous Environment. In: Filizola, M. (eds) G Protein-Coupled Receptors in Drug Discovery. Methods in Molecular Biology, vol 1335. Humana Press, New York, NY. https://doi.org/10.1007/978-1-4939-2914-6_12

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  • DOI: https://doi.org/10.1007/978-1-4939-2914-6_12

  • Publisher Name: Humana Press, New York, NY

  • Print ISBN: 978-1-4939-2913-9

  • Online ISBN: 978-1-4939-2914-6

  • eBook Packages: Springer Protocols

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