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Opioid Receptor Signal Transduction Mechanisms

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The Opiate Receptors

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

Abstract

The myriad functions of morphine and its congeners are the consequences of the drug interacting with the three opioid receptors. In order to develop a perfect analgesic compound that mediates its function via these receptors, the mechanisms by which signaling occurs and the regulation of the signals must be fully elucidated. Since opioid receptors are members of the G protein-coupled receptor (GPCR) superfamily, many of their signaling processes mimic those of other GPCRs. However, it is apparent from recent proteomic and other studies that opioid receptors, similar to several GPCRs in the rhodopsin subfamily, exist in signaling complexes. These signaling complexes include the oligomerization of the opioid receptors with each other, with other GPCRs, or with other cellular proteins, such as β-arrestin or regulators of G protein signaling (RGS) that could alter or modulate the final receptor signals. In addition, accumulating evidence points to the presence of an agonist-selective signaling process with the opioid receptors. In this chapter, we will review the classical signaling mechanisms of opioid receptors, the various effectors that are regulated by opioid receptors, and their possible roles in the in vivo functions of drugs, and cellular regulators that could influence the amplitude and duration of the signals. We will examine recent data that support the existence of opioid receptor signaling complexes, or “receptosomes,” in the transduction of opioid receptor signals. Finally, evidence for ligand-selective signaling and its implication in future drug development will be discussed.

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Acknowledgement

The research for this article was supported in part by grants provided by the National Institute on Drug Abuse, DA007339 and DA016674. PYL is a recipient of a Senior Scientist Award from NIDA, K05-DA000513.

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  1. Department of Pharmacology, University of Minnesota Medical School, Minneapolis, MN, 55455-0217, USA

    Ping-Yee Law

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    Gavril W. Pasternak

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Law, PY. (2011). Opioid Receptor Signal Transduction Mechanisms. In: Pasternak, G. (eds) The Opiate Receptors. The Receptors. Humana Press, Totowa, NJ. https://doi.org/10.1007/978-1-60761-993-2_9

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