Morphine-activated opioid receptors elude desensitization by β-arrestin

Jennifer Whistler, Mark Von Zastrow

Research output: Contribution to journalArticlepeer-review

306 Scopus citations

Abstract

μ opioid receptors are targets of native opioid peptides and addictive analgesic drugs. A major clinical liability of opiate drugs is their ability to cause physiological tolerance. Individual opiates, such as morphine and etorphine, differ both in their ability to promote physiological tolerance and in their effects on receptor regulation by endocytosis. Here, we demonstrate that arrestins play a fundamental role in mediating this agonist- selective regulation and that morphine-activated μ receptors fail to undergo arrestin-dependent uncoupling from cognate G proteins. Thus, highly addictive opiate drugs elude a fundamental mode of physiological regulation that is mediated by agonist-specific interaction of opioid receptors with arrestins.

Original languageEnglish (US)
Pages (from-to)9914-9919
Number of pages6
JournalProceedings of the National Academy of Sciences of the United States of America
Volume95
Issue number17
DOIs
StatePublished - Aug 18 1998
Externally publishedYes

ASJC Scopus subject areas

  • General

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