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Research ArticleCELLULAR AND MOLECULAR

Gz Can Mediate the Acute Actions of μ- and κ-Opioids but Is Not Involved in Opioid-Induced Adenylyl Cyclase Supersensitization

Prudence H. Tso and Yung H. Wong
Journal of Pharmacology and Experimental Therapeutics October 2000, 295 (1) 168-176;
Prudence H. Tso
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Yung H. Wong
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Abstract

The three subtypes of opioid receptors (δ, μ, and κ) are known to regulate multiple effectors through either pertussis toxin-sensitive or -insensitive G proteins. In opioid-induced inhibition of adenylyl cyclase, both Gi and Gz proteins can serve as the signal transducer. Our previous study showed that opioid-induced adenylyl cyclase supersensitization in human embryonic kidney (HEK) 293 cells expressing the δ-opioid receptor requires Gi but not Gz proteins. Herein, we studied the ability of μ- and κ-opioid receptors to regulate the activities of adenylyl cyclase through Gz. In HEK 293 cells coexpressing Gzwith the μ- or κ-opioid receptors, opioid agonists induced inhibition of adenylyl cyclase in a pertussis toxin-insensitive manner. However, adenylyl cyclase supersensitization induced by chronic opioid treatments remained sensitive to pertussis toxin. We also showed that the responsiveness of cAMP-dependent response element-binding proteins to forskolin was not altered after prolonged opioid treatment but was higher in cells coexpressing Gz. Although the μ- and κ-opioid receptors mediated acute activation of extracellular signal-regulated protein kinase 1/2 via both Gi and Gz, these responses were abolished by chronic opioid treatment. These studies showed that Gzcould mediate acute actions of μ- and κ-opioids but Gzalone was insufficient to mediate adenylyl cyclase supersensitization induced by the chronic activation of opioid receptors.

Footnotes

  • Send reprint requests to: Dr. Y. H. Wong, Department of Biochemistry, Hong Kong University of Science and Technology, Clear Water Bay, Kowloon, Hong Kong, China. E-mail:boyung{at}ust.hk

  • ↵1 This study was supported in part by grants from the Research Grants Council of Hong Kong (HKUST 567/95M and HKUST 653/96M) and the Hong Kong Jockey Club.

  • Abbreviations:
    AC
    adenylyl cyclase
    CREB
    cAMP-dependent response element-binding protein
    ERK
    extracellular signal-regulated protein kinase
    PTX
    pertussis toxin
    HEK
    human embryonic kidney
    DAGO
    [d-Ala2,N-Me-Phe4,Gly5-ol]-enkephalin
    MAPK
    mitogen-activated protein kinase
    MEM
    minimum essential medium
    DTT
    dithiothreitol
    • Received March 2, 2000.
    • Accepted June 12, 2000.
  • The American Society for Pharmacology and Experimental Therapeutics
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Journal of Pharmacology and Experimental Therapeutics: 295 (1)
Journal of Pharmacology and Experimental Therapeutics
Vol. 295, Issue 1
1 Oct 2000
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Research ArticleCELLULAR AND MOLECULAR

Gz Can Mediate the Acute Actions of μ- and κ-Opioids but Is Not Involved in Opioid-Induced Adenylyl Cyclase Supersensitization

Prudence H. Tso and Yung H. Wong
Journal of Pharmacology and Experimental Therapeutics October 1, 2000, 295 (1) 168-176;

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Research ArticleCELLULAR AND MOLECULAR

Gz Can Mediate the Acute Actions of μ- and κ-Opioids but Is Not Involved in Opioid-Induced Adenylyl Cyclase Supersensitization

Prudence H. Tso and Yung H. Wong
Journal of Pharmacology and Experimental Therapeutics October 1, 2000, 295 (1) 168-176;
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