Enhanced morphine analgesia in mice lacking beta-arrestin 2.

Published

Journal Article

The ability of morphine to alleviate pain is mediated through a heterotrimeric guanine nucleotide binding protein (G protein)-coupled heptahelical receptor (GPCR), the mu opioid receptor (muOR). The efficiency of GPCR signaling is tightly regulated and ultimately limited by the coordinated phosphorylation of the receptors by specific GPCR kinases and the subsequent interaction of the phosphorylated receptors with beta-arrestin 1 and beta-arrestin 2. Functional deletion of the beta-arrestin 2 gene in mice resulted in remarkable potentiation and prolongation of the analgesic effect of morphine, suggesting that muOR desensitization was impaired. These results provide evidence in vivo for the physiological importance of beta-arrestin 2 in regulating the function of a specific GPCR, the muOR. Moreover, they suggest that inhibition of beta-arrestin 2 function might lead to enhanced analgesic effectiveness of morphine and provide potential new avenues for the study and treatment of pain, narcotic tolerance, and dependence.

Full Text

Duke Authors

Cited Authors

  • Bohn, LM; Lefkowitz, RJ; Gainetdinov, RR; Peppel, K; Caron, MG; Lin, FT

Published Date

  • December 24, 1999

Published In

Volume / Issue

  • 286 / 5449

Start / End Page

  • 2495 - 2498

PubMed ID

  • 10617462

Pubmed Central ID

  • 10617462

International Standard Serial Number (ISSN)

  • 0036-8075

Digital Object Identifier (DOI)

  • 10.1126/science.286.5449.2495

Language

  • eng

Conference Location

  • United States