前列腺素E2对血小板的腺苷酸环化酶既有刺激作用又有抑制作用：对克隆的EP4和EP3前列腺素受体亚型的作用比较。

Prostaglandin E2 both stimulates and inhibits adenyl cyclase on platelets: comparison of effects on cloned EP4 and EP3 prostaglandin receptor subtypes.

作者信息

Mao G F, Jin J G, Bastepe M, Ortiz-Vega S, Ashby B

机构信息

Department of Pharmacology, Temple University School of Medicine, Philadelphia, PA 19140, USA.

出版信息

Prostaglandins. 1996 Sep;52(3):175-85. doi: 10.1016/s0090-6980(96)00095-0.

DOI:10.1016/s0090-6980(96)00095-0

PMID:8908618

Abstract

The effects of prostaglandin E2 (PGE2) on platelet cyclic AMP formation were examined and compared with effects on cloned prostaglandin receptors. PGE2 gave a weak stimulation of adenyl cyclase in platelets compared with the PGI2 analog Iloprost. In the presence of the adenyl cyclase stimulator forskolin, the response to PGE2 was amplified in a synergistic manner. By contrast, in the presence of Iloprost, PGE2 inhibited cyclic AMP formation. We postulate that the weak platelet response to PGE2 is due to co-localization of a PGE2 receptor that couples to stimulation of adenyl cyclase with the EP3 prostaglandin receptor that binds PGE2 tightly and inhibits adenyl cyclase. In support of this postulate, we compared the responses obtained with platelets with those of cloned EP4 (stimulatory) and EP3 (inhibitory) prostaglandin receptor subtypes and show similar dose-response curves for stimulation and inhibition of cyclic AMP formation between platelets and cloned receptors.

摘要

研究了前列腺素E2（PGE2）对血小板环磷酸腺苷（cAMP）生成的影响，并与对克隆前列腺素受体的影响进行了比较。与前列环素（PGI2）类似物伊洛前列素相比，PGE2对血小板腺苷酸环化酶的刺激作用较弱。在腺苷酸环化酶刺激剂福斯高林存在的情况下，对PGE2的反应以协同方式放大。相比之下，在伊洛前列素存在的情况下，PGE2抑制cAMP生成。我们推测，血小板对PGE2的反应较弱是由于与腺苷酸环化酶刺激偶联的PGE2受体与紧密结合PGE2并抑制腺苷酸环化酶的EP3前列腺素受体共定位所致。为支持这一推测，我们比较了血小板与克隆的EP4（刺激性）和EP3（抑制性）前列腺素受体亚型的反应，结果显示血小板和克隆受体在刺激和抑制cAMP生成方面具有相似的剂量反应曲线。