Ahluwalia A, Perretti M
Department of Biochemical Pharmacology, William Harvey Research Institute, Medical College of St. Bartholomew's Hospital, London, England.
J Pharmacol Exp Ther. 1994 Mar;268(3):1526-31.
The effects of prostaglandin E1 (PGE1) and certain PGE-analogs on edema formation were investigated in mouse and rat skin. In the mouse, intradermal administration of both zymosan-activated serum (ZAS) (5-50% per site) and platelet-activating factor (PAF) (0.1-5.0 nmol/site) caused dose-related increases in edema formation. PGE1 (0.003-3.0 nmol/site) caused a dose-related inhibition of the edema response to ZAS, whereas a dose of 0.3 nmol potentiated the edema response to PAF. Sulprostone, which is selective for EP1 and EP3 PGE-receptors, produced a potent inhibition of the edema responses to both ZAS (80%) and PAF (60%). Misoprostol, which is selective for both EP2- and EP3-receptors, inhibited the edema response to ZAS (> 40%) but had no effect on the response to PAF. Treatment of mice with the thromboxane A2-receptor antagonist GR32191B did not modify the anti-inflammatory activity of PGE1 or sulprostone. In the rat skin model, PGE1 produced only potentiation of the responses to both ZAS and PAF. However, sulprostone displayed significant inhibitory effects on the edema responses to both stimuli (40-50%). From these data we propose that the anti-inflammatory activity of PGE1 and of the two analogs sulprostone and misoprostol may be mediated via activation of the contractile EP3-receptor. Differences in the responses to prostanoids from one species to another may reflect differences in the relative densities of receptor subtypes mediating opposite effects.
研究了前列腺素E1（PGE1）和某些PGE类似物对小鼠和大鼠皮肤水肿形成的影响。在小鼠中，皮内注射酵母聚糖激活血清（ZAS）（每个部位5%-50%）和血小板活化因子（PAF）（0.1-5.0 nmol/部位）均导致水肿形成呈剂量相关增加。PGE1（0.003-3.0 nmol/部位）导致对ZAS的水肿反应呈剂量相关抑制，而0.3 nmol的剂量则增强了对PAF的水肿反应。对EP1和EP3 PGE受体具有选择性的舒前列素对ZAS（80%）和PAF（60%）的水肿反应均产生了强效抑制作用。对EP2和EP3受体均具有选择性的米索前列醇抑制了对ZAS的水肿反应（>40%），但对PAF反应无影响。用血栓素A2受体拮抗剂GR32191B处理小鼠并未改变PGE1或舒前列素的抗炎活性。在大鼠皮肤模型中，PGE1仅增强了对ZAS和PAF的反应。然而，舒前列素对两种刺激的水肿反应均显示出显著的抑制作用（40%-50%）。根据这些数据，我们提出PGE1以及舒前列素和米索前列醇这两种类似物的抗炎活性可能是通过收缩性EP3受体的激活介导的。不同物种对前列腺素反应的差异可能反映了介导相反作用的受体亚型相对密度的差异。
