期刊
EUROPEAN JOURNAL OF PHARMACOLOGY
卷 525, 期 1-3, 页码 18-23出版社
ELSEVIER SCIENCE BV
DOI: 10.1016/j.ejphar.2005.09.057
关键词
alpha(1)-adrenoceptor; receptor phosphorylation; protein kinase C; protein phosphatase; desensitization; phosphatidylinositol 3-kinase
Okadaic acid, a protein phosphatase inhibitor, and phorbol myristate acetate, an activator of protein kinase C, increased the phosphorylation state of alpha(1A)-drenergic receptors. The effects of these agents were of similar magnitude but that of okadaic acid developed more slowly. Wortmannin (inhibitor of phosphomositide 3-kinase), but not staurosporine (inhibitor of protein kinase C), abolished the effect of okadaic acid on the alpha(1A)-adrenoceptor phosphorylation state. The effect of phorbol myristate acetate on this parameter was blocked by staurosporine and only partially inhibited by wortmannin. Okadaic acid markedly increased the co-immunoprecipitation of both the catalytic and regulatory subunits of phosphatidylinositol 3-kinase and of Akt/protein kinase B with the adrenoceptor and only marginally increases receptor association with protein kinase C epsilon. Okadaic acid induced desensitization of alpha(1A)-adrenoceptors as evidenced by a decreased ability of noradrenaline to increase intracellular calcium. Such desensitization was fully reverted by wortmannin. Our data indicate that inhibition of serine/threonine protein phosphatases increases the phosphorylation state of alpha(1A)-adrenergic receptor and alters the adrenoceptor function. (c) 2005 Elsevier B.V. All rights reserved.
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