Goh Y, Nakajima M
Shionogi Research Laboratories, Osaka, Japan.
Exp Eye Res. 1990 Nov;51(5):585-90. doi: 10.1016/0014-4835(90)90089-d.
Effects of prostaglandin (PG) D2 analogues on the adenylate cyclase activity in membrane fractions of the iris-ciliary body complex were studied. PGD2 dose-dependently activated the adenylate cyclase with a maximal activity increase of about 60%. The concentration required to cause a half-maximal stimulation (EC50) was about 5 x 10(-7) M. The stimulatory effect of PGD2 was totally dependent on GTP with EC50 for GTP at about 10(-7) M. The rank order of potency of PGD2 analogues for stimulating the adenylate cyclase and BW245C (a selective PGD2 agonist) greater than PGD3 greater than PGD2 greater than 9 beta-PGD2. PGD2 metabolites and PGD2 analogues which have little hypotensive activity were essentially ineffective in stimulating the adenylate cyclase. This rank order was strikingly similar to that reported previously for their intraocular pressure-lowering effects. One exception was PGD2 methylester. This compound, though reportedly effective in reducing IOP, failed to activate the adenylate cyclase by itself, presumably because its hypotensive effect is due to its hydrolyzed product, PGD2. These results indicate that the abilities of PGD2 analogues to stimulate the adenylate cyclase of the iris-ciliary body complex in GTP-dependent manner are highly correlated with their ocular hypotensive activities, and suggest that a PGD2 receptor-stimulatory GTP-binding protein-adenylate cyclase complex is involved in the PGD2-induced ocular hypotension.
研究了前列腺素（PG）D2类似物对虹膜-睫状体复合体膜组分中腺苷酸环化酶活性的影响。PGD2以剂量依赖性方式激活腺苷酸环化酶，最大活性增加约60%。引起半数最大刺激所需的浓度（EC50）约为5×10（-7）M。PGD2的刺激作用完全依赖于GTP，GTP的EC50约为10（-7）M。PGD2类似物刺激腺苷酸环化酶的效力顺序为BW245C（一种选择性PGD2激动剂）＞PGD3＞PGD2＞9β-PGD2。几乎没有降压活性的PGD2代谢产物和PGD2类似物在刺激腺苷酸环化酶方面基本无效。这个效力顺序与先前报道的它们的降眼压作用顺序惊人地相似。一个例外是PGD2甲酯。据报道该化合物可有效降低眼压，但其本身未能激活腺苷酸环化酶，推测是因为其降压作用归因于其水解产物PGD2。这些结果表明，PGD2类似物以GTP依赖性方式刺激虹膜-睫状体复合体腺苷酸环化酶的能力与其降眼压活性高度相关，并提示PGD2受体刺激型GTP结合蛋白-腺苷酸环化酶复合物参与了PGD2诱导的眼压降低过程。
