Basal phosphorylation of mu opioid receptor is agonist modulated and Ca2+-dependent

被引:39
作者
Wang, ZJ
Arden, J
Sadee, W
机构
[1] UNIV CALIF SAN FRANCISCO, DEPT BIOPHARMACEUT SCI, SAN FRANCISCO, CA 94143 USA
[2] UNIV CALIF SAN FRANCISCO, DEPT PHARMACEUT CHEM, SAN FRANCISCO, CA 94143 USA
来源
FEBS LETTERS | 1996年 / 387卷 / 01期
关键词
mu opioid receptor; receptor phosphorylation; Ca2+ dependent kinase; narcotic dependence and tolerance;
D O I
10.1016/0014-5793(96)00467-X
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
The mu opioid receptor was shown to be phosphorylated at a basal rate in the absence of agonist, measured in permeabilized HEK293 cells transfected with an epitope tagged mu receptor (EE-mu) [Arden, J., Segredo, V., Wang, Z., Lameh, J. and Sadee, W. (1995) J. Neurochem. 65, 1636-1645]. In the present study, basal phosphorylation was found to be Ca2+ dependent; however, several inhibitors of protein kinase C and Ca2+-calmodulin dependent kinases failed to affect basal mu receptor phosphorylation. Thus, the basal mu receptor phosphorylating activity differed from the main kinases involved in receptor regulation. The general kinase inhibitor H7 (100 mu M) suppressed basal mu receptor phosphorylation. Pretreatment with the agonist morphine, followed by drug removal, resulted in a sustained increase of basal mu receptor phosphorylation. The gradual agonist dependent modulation of basal mu receptor phosphorylation suggests a novel regulatory mechanism which may play a role in narcotic tolerance and dependence.
引用
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页码:53 / 57
页数:5
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