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Enhanced morphine analgesia in mice lacking beta-arrestin 2.

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.

Pubmed ID: 10617462


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


Science (New York, N.Y.)

Publication Data

December 24, 1999

Associated Grants

  • Agency: NIDA NIH HHS, Id: F32 DA006023
  • Agency: NHLBI NIH HHS, Id: HL16037
  • Agency: NINDS NIH HHS, Id: NS 19576

Mesh Terms

  • Analgesia
  • Analgesics, Opioid
  • Animals
  • Arrestins
  • Binding Sites
  • Body Temperature
  • Brain
  • Enkephalin, Ala(2)-MePhe(4)-Gly(5)-
  • GTP-Binding Proteins
  • Guanosine 5'-O-(3-Thiotriphosphate)
  • Mice
  • Mice, Inbred C57BL
  • Mice, Knockout
  • Morphine
  • Naloxone
  • Narcotic Antagonists
  • Pain Measurement
  • Pain Threshold
  • Phosphorylation
  • Receptors, Opioid, mu
  • Signal Transduction