Involvement of kappa opioid receptors in the inhibition of receptor desensitization and PKC activation induced by repeated morphine treatment.

Involvement of kappa opioid receptors in the inhibition of receptor desensitization and PKC activation induced by repeated morphine treatment. Research Abstract Details 

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Involvement of kappa opioid receptors in the inhibition of receptor desensitization and PKC activation induced by repeated morphine treatment. Abstract Text:

Analgesic tolerance to morphine can develop from long-term use of this drug for the treatment of pain. Many reports have shown that stimulation of the kappa opioid receptor (KOR) suppresses development of analgesic tolerance to morphine. Here, we studied the KOR-mediated inhibition of morphine tolerance during repeated morphine treatment, with a focus on desensitization of the receptor. The development of analgesic tolerance to morphine during repeated morphine administration (10 mg kg(-1) s.c.) was completely suppressed by U-50488H (2 mg kg(-1) i.p.), a KOR agonist. The decrease in [(35)S] GTP(gamma)S binding activity stimulated by the mu opioid receptor (MOR) agonist [D-Ala(2), N-Me-Phe(4), Gly(5)-ol]-enkephalin (DAMGO) was also significantly inhibited by U-50488H. These results indicate that stimulation of KOR caused by repeated morphine treatment either inhibits MOR desensitization or accelerates recycling of MOR on the cell surface, thereby suppressing morphine tolerance. Furthermore, we found that activity of protein kinase C (PKC) was significantly decreased in mice treated with both U-50488H and morphine. These results suggest that the mechanisms underlying KOR-mediated inhibition of analgesic tolerance to morphine may be partly due to suppression of PKC activation and prevention of receptor desensitization.

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Involvement of kappa opioid receptors in the inhibition of receptor desensitization and PKC activation induced by repeated morphine treatment. Journal Published:

PUBLICATION TYPE: Journal Article

Journal: The Journal of pharmacy and pharmacology

VOLUME: 60

Page Numbers: 1183-8

Journal Abbreviation: J. Pharm. Pharmacol.

ISSN: 0022-3573

DAY: 22

MONTH: Sep

YEAR: 2008

Involvement of kappa opioid receptors in the inhibition of receptor desensitization and PKC activation induced by repeated morphine treatment. Information

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LANGUAGE: eng

NlmUniqueID: 376363

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Grant and Affiliation Information for Involvement of kappa opioid receptors in the inhibition of receptor desensitization and PKC activation induced by repeated morphine treatment.

AFFILIATION: Department of Clinical Pharmacy, Faculty of Pharmaceutical Sciences, Kobe Gakuin University, 1-1-3 Minatojima, Chuo-ku, Kobe, 650-8586, Japan.

Country: England

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MEDLINETA: J Pharm Pharmacol

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