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The interaction of the mu-opioid receptor and G protein is altered after chronic morphine treatment in rats

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Summary

The interaction of µ-opioid receptors and G proteins after chronic morphine treatment was investigated in rats. Male Sprague-Dawley rats (200–260 g) were rendered tolerant to morphine by i.p. injections of increasing doses of morphine twice daily for 4 or 6 days. During this period, there was a time-dependent increase in the AD50 values for morphine to inhibit the tail-flick response. In addition, in vitro µ-opioid receptor binding to midbrain P2 membranes from these animals revealed that the ability of 10 μmol/l Gpp(NH)p (guanyl-5′-yl imidodiphosphate) to decrease [3H]DAMGO (TyrD-Ala-Gly-McPhe-Gly-ol) binding affinity, i.e., the ratio K d(+Gpp(NH)p)/K d(−Gpp(NH)p), decreased significantly from the control value of 3.68±0.40 to 2.37±0.35 after 6 days of morphine treatment (P<0.05).

The ability of DAMGO to stimulate low K m GTPase activity was also investigated. The EC50 significantly increased from 2.7± 1.1 × 10−8 mol/l in the control group to 10.8±1.5 × 10−8 mol/l after 4 days of morphine treatment and was further increased to 13.5±2.1 × 10−8 mol/l after 6 days of morphine treatment. The maximal stimulation by DAMGO decreased significantly from 18.0±1.7% to 12.8± 1.6% after 6 days of morphine treatment.

These results indicate that the interaction between µ-opioid receptors and G proteins had been altered after chronic morphine treatment.

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Authors and Affiliations

  1. Department of Pharmacology, National Defense Medical Center, P.O. Box 90048-504, Taipei, Taiwan, R.O.C.

    Pao-Luh Tao & Chia-Rong Lee

  2. Department of Pharmacology, University of Minnesota, Minneapolis, MN, USA

    Ping-Yee Law & Horace H. Loh

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  1. Pao-Luh Tao
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  2. Chia-Rong Lee
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  3. Ping-Yee Law
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  4. Horace H. Loh
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Correspondence to: P.-L. Tao at the above address

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Tao, PL., Lee, CR., Law, PY. et al. The interaction of the mu-opioid receptor and G protein is altered after chronic morphine treatment in rats. Naunyn-Schmiedeberg's Arch Pharmacol 348, 504–508 (1993). https://doi.org/10.1007/BF00173210

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  • DOI: https://doi.org/10.1007/BF00173210

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