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

The Journal of Pharmacy and Pharmacology
Wakako HamabeShogo Tokuyama

Abstract

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 [35S] GTPgammaS binding activity stimulated by the mu opioid receptor (MOR) agonist [D-Ala2, N-Me-Phe4, Gly5-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 ...Continue Reading

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Aug 30, 2007·The Journal of Pharmacy and Pharmacology·Shogo TokuyamaWakako Hamabe

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Citations

May 10, 2011·European Journal of Pharmacology·Wakako Fujita-HamabeShogo Tokuyama
Mar 17, 2012·The Journal of Pharmacy and Pharmacology·Wakako Fujita-HamabeShogo Tokuyama
Aug 31, 2013·Life Sciences·Shinichi HaradaShogo Tokuyama
Oct 2, 2009·Peptides·Richard J Bodnar

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