Chronic opioid treatment may uncouple opioid receptors and G-proteins: evidence from radiation inactivation analysis

Pao Luh Tao, Li Ren Chang, Yen Ping Chou, Ping-Yee Law, Horace H Loh

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22 Scopus citations


Radiation inactivation (target size analysis) was used in this study to determine whether uncoupling of opioid receptor and G-protein is a contributing mechanism to opioid tolerance. Male Sprague-Dawley rats (160-260 g) were rendered tolerant to morphine or [D-Ala2, D-Leu5]enkephalin (DADLE) by multiple i.p. or i.c.v. injections twice a day for 6 or 5 days. Control rats were injected with saline instead of opioids. The animals were killed, the midbrains excised and pooled together for each group. The washed P2 membranes were suspended in buffer and irradiated with 1-10 Mrad doses of 60Co irradiation, following which μ- or δ-opioid receptor binding activity of each sample was assayed. The molecular weight of the receptor was calculated from a standard irradiation curve constructed using several enzyme markers of known molecular weight. We found that the functional molecular size of μ-opioid receptor significantly decreased from 349 kDa to 228 kDa after 6 days of chronic morphine treatment, while, the molecular size of δ-opioid receptor decreased from 303 kDa to 223 kDa after 5 days of chronic DADLE treatment. These results are consistent with the uncoupling of opioid receptor from G-protein during chronic opioid treatment.

Original languageEnglish (US)
Pages (from-to)233-238
Number of pages6
JournalEuropean Journal of Pharmacology: Molecular Pharmacology
Issue number3
StatePublished - Aug 15 1993

Bibliographical note

Funding Information:
The present studies were supported by a Grant NSC 76-0412-B016-18 from the National Science Council, Taipei, Taiwan, Republic of China. We are grateful to Dr. Ying-kai Fu and the stuff at the Institute of Nuclear Energy Research, Lung-tan, Taiwan, R.O.C. for providing the facilities for irradiation, and for their technical assistance.


  • (Uncoupling)
  • G-protein
  • Opioid receptor
  • Radiation inactivation
  • Tolerance


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