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- W201331485 abstract "The μ-opioid receptor is the G protein coupled receptor (GPCR) responsible for the analgesic, rewarding and unwanted effects of morphine and similar drugs. Constitutive activity of GPCRs is a phenomenon that likely reflects receptors spontaneous adopting conformations that can activate G proteins, and is likely to be common to most if not all GPCRs. Basal constitutive activity has been observed in some systems with μ-opioid receptors, and constitutive activity is expressed by mutant μ-opioid receptors with amino acid substitutions in regions known to be important for signaling. However, μ-opioid receptors are unique in that a putative constitutively active state of the receptor, the μ*-state, has been suggested to be induced by prolonged agonist treatment. The μ*-state is thought to contribute to processes underlying adaptation to and withdrawal from opioid treatment, and may have a ligand sensitivity distinct from basal constitutive activity of the μ-opioid receptor or that exhibited by μ-opioid receptor mutants. In this chapter, we outline methods for measuring constitutively active μ-opioid receptors, including some that take advantage of the fairly direct coupling of the receptor to ion channels. We also briefly summarize the pharmacology of the different constitutively active μ-opioid receptor states, and highlight the areas where we need to know more. We hope that a better understanding of constitutive activity at the μ-opioid receptor may provide information useful in developing ligands that access subsets of receptor conformations, offering the potential to fine-tune opioid pharmacotherapy." @default.
- W201331485 created "2016-06-24" @default.
- W201331485 creator A5010714266 @default.
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- W201331485 date "2010-01-01" @default.
- W201331485 modified "2023-09-23" @default.
- W201331485 title "Constitutively Active μ-Opioid Receptors" @default.
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- W201331485 doi "https://doi.org/10.1016/b978-0-12-381298-8.00022-8" @default.
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