Pawlotsky J M, Ruszniewski P, Reyl-Desmars F, Bourgeois M, Lewin M J
Unité de Recherches de Gastroentérologie, INSERM U.10, Hôpital Bichat, Paris, France.
Dig Dis Sci. 1993 Feb;38(2):316-20. doi: 10.1007/BF01307550.
Prostaglandins of the E series (PGE) are known to stimulate intestinal water and electrolyte secretions via the activation of the enterocyte adenylate cyclase. Their methylated synthetic analogs misoprostol and enprostil induced diarrhea in 5-13% of the patients in most clinical studies. In order to elucidate the role of PGE-adenylate cyclase interaction in these phenomena, we studied the stimulation of adenylate cyclase by native prostaglandin E2 (PGE2) and synthetic PGE analogs on isolated guinea pig intestinal epithelial cells. PGE2 stimulation of adenylate cyclase was dose-dependent, reaching a maximum for 3 x 10(-4) M, with an EC50 of 3.7 x 10(-6) M. The Hill analysis of the concentration-response curve gave a straight line, with a slope close to 1. The effect of PGE2 was strictly additive to that of 10(-5) M forskolin, whereas it was decreased in terms of potency by 10(-9) M cholera toxin. Somatostatin-14 markedly inhibited PGE2 stimulation by 37% and 45% with 10(-9) M and 10(-6) M, respectively. The two PGE methylated analogs misoprostol and enprostil were less potent than PGE2 in stimulating adenylate cyclase in our model.(ABSTRACT TRUNCATED AT 250 WORDS)
已知E系列前列腺素（PGE）可通过激活肠上皮细胞腺苷酸环化酶来刺激肠道水和电解质分泌。在大多数临床研究中，其甲基化合成类似物米索前列醇和恩前列素在5%-13%的患者中会引起腹泻。为了阐明PGE-腺苷酸环化酶相互作用在这些现象中的作用，我们研究了天然前列腺素E2（PGE2）和合成PGE类似物对分离的豚鼠肠上皮细胞腺苷酸环化酶的刺激作用。PGE2对腺苷酸环化酶的刺激呈剂量依赖性，在3×10^(-4) M时达到最大值，EC50为3.7×10^(-6) M。对浓度-反应曲线进行希尔分析得到一条直线，斜率接近1。PGE2的作用与10^(-5) M福斯可林的作用严格相加，而其效力在10^(-9) M霍乱毒素作用下降低。生长抑素-14分别以10^(-9) M和10^(-6) M显著抑制PGE2刺激37%和45%。在我们的模型中，两种PGE甲基化类似物米索前列醇和恩前列素在刺激腺苷酸环化酶方面的效力低于PGE2。（摘要截短于250字）
