Endocytosis of the mu opioid receptor reduces tolerance and a cellular hallmark of opiate withdrawal

Andrew K. Finn, Jennifer Whistler

Research output: Contribution to journalArticle

222 Citations (Scopus)

Abstract

Morphine is unusual in its failure to promote robust desensitization and endocytosis of the mu opioid receptor (MOR), processes that for many receptors contribute directly to tolerance. This apparent paradox has led us to revise the idea that receptor desensitization and endocytosis are solely responsible for tolerance and withdrawal to morphine, and instead test the hypothesis that these side effects occur due to abnormally prolonged MOR signaling. We report here that MOR mutations that facilitate endocytosis reduce the development of cellular tolerance and cAMP superactivation, a cellular hallmark of withdrawal. Moreover, mutant receptors with reduced endocytosis produce exacerbated superactivation. These data demonstrate a critical role for receptor endocytosis in the development of adverse side effects associated with prolonged opiate use.

Original languageEnglish (US)
Pages (from-to)829-839
Number of pages11
JournalNeuron
Volume32
Issue number5
DOIs
StatePublished - Dec 6 2001
Externally publishedYes

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Opiate Alkaloids
mu Opioid Receptor
Endocytosis
Morphine
Mutation

ASJC Scopus subject areas

  • Neuroscience(all)

Cite this

Endocytosis of the mu opioid receptor reduces tolerance and a cellular hallmark of opiate withdrawal. / Finn, Andrew K.; Whistler, Jennifer.

In: Neuron, Vol. 32, No. 5, 06.12.2001, p. 829-839.

Research output: Contribution to journalArticle

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