脑内皮细胞培养。II. 腺苷酸环化酶对前列腺素的反应及其与肾上腺素能系统的相互作用。

Cerebral endothelial cell culture. II. Adenylate cyclase response to prostaglandins and their interaction with the adrenergic system.

作者信息

Karnushina I L, Spatz M, Bembry J

出版信息

Life Sci. 1983 Mar 28;32(13):1427-35. doi: 10.1016/0024-3205(83)90907-4.

Abstract

The response of endothelial adenylate cyclase (AC) to prostaglandins (PGE1, PGE2, PGF1 alpha, PGF2 alpha, PGD2 and PGI2) and the relationship of PGE2 to adrenergic systems were investigated in cerebrovascular endothelial cultures. E-type prostaglandins and PGI2 were more effective in stimulating endothelial AC (EC50 = 3 x 10(-7)M, and 3 x 10(-6)M, respectively) than prostaglandins of the F-series and PGD2 which activated AC at high doses only. A modulation of endothelial AC response to either PGE2 or norepinephrine (NE) was observed in the presence of both agents in the system. It was manifested by a dose-dependent NE inhibition of the PGE2-stimulated formation of cAMP, which was partially restored by phentolamine. Alpha and beta-adrenergic agonists (alpha, clonidine and 6-fluoronorepinephrine; beta, isoproterenol) also partly blocked while forskolin and PGE2 synergistically stimulated the production of cAMP in the endothelial cultures. These findings strongly suggest that the interaction of prostaglandins and alpha- and beta-adrenergic agonists with the AC system in cerebrovascular endothelium may play a role in the regulation of the cerebral microcirculation and/or blood pressure.

摘要

在脑血管内皮细胞培养物中，研究了内皮腺苷酸环化酶（AC）对前列腺素（PGE1、PGE2、PGF1α、PGF2α、PGD2和PGI2）的反应以及PGE2与肾上腺素能系统的关系。E型前列腺素和PGI2在刺激内皮AC方面比F系列前列腺素和PGD2更有效（EC50分别为3×10−7M和3×10−6M），后者仅在高剂量时激活AC。在系统中同时存在这两种药物的情况下，观察到内皮AC对PGE2或去甲肾上腺素（NE）的反应受到调节。其表现为NE对PGE2刺激的cAMP形成具有剂量依赖性抑制作用，酚妥拉明可部分恢复该作用。α和β肾上腺素能激动剂（α，可乐定和6-氟去甲肾上腺素；β，异丙肾上腺素）也部分阻断了内皮细胞培养物中cAMP的产生，而福斯可林和PGE2则协同刺激其产生。这些发现强烈表明，前列腺素以及α和β肾上腺素能激动剂与脑血管内皮中的AC系统相互作用可能在脑微循环和/或血压调节中发挥作用。