前列腺素E2的甲基化类似物与胃黏膜屏障

Methylated analogues of prostaglandin E2 and the gastric mucosal barrier.

作者信息

Kenyon G S, Ansell I F, Carter D C

出版信息

Prostaglandins. 1978 May;15(5):779-94. doi: 10.1016/0090-6980(78)90144-2.

Abstract

15(R)-methyl PGE2 methyl ester (15MPG) and 16,16-dimethyl PGE2 methyl ester (16DMPG) were assessed for their effect on gastric mucosal permeability to Na+ and H+ in dogs prepared by antrectomy and vagally-denervated fundic pouches. 15MPG did not increase mucosal permeability to either ion when given topically (18.75-300 microgram) or parenterally (30 microgram), and did not affect permeability increases induced by topical 5mM sodium taurocholate in acid solution. 16DMPG caused significant increases in net Na+ gain when given topically (18.75-75 microgram) but did not affect net H+ loss from the pouch lumen. Attempts to use higher doses of 16DMPG were abandoned because of bleeding from the pouch, and perforation in one animal. It is conceivable that 16DMPG could cause adverse effects on the gastric mucosal barrier if used to suppress gastric secretion therapeutically. 15MPG does not share this potentially harmful property and remains worthy of further study as an inhibitor of gastric secretion with therapeutic promise.

摘要

对15（R）-甲基前列腺素E2甲酯（15MPG）和16,16-二甲基前列腺素E2甲酯（16DMPG）进行了评估，观察它们对经胃窦切除和迷走神经切断的胃底囊制备的犬胃黏膜对Na⁺和H⁺通透性的影响。局部给予15MPG（18.75 - 300微克）或经胃肠外给予（30微克）时，均未增加黏膜对任何一种离子的通透性，且不影响酸性溶液中局部给予5mM牛磺胆酸钠所诱导的通透性增加。局部给予16DMPG（18.75 - 75微克）时，可导致净Na⁺摄取显著增加，但不影响胃囊腔中的净H⁺丢失。由于胃囊出血以及一只动物出现穿孔，放弃了使用更高剂量16DMPG的尝试。可以想象，如果将16DMPG用于治疗性抑制胃酸分泌，可能会对胃黏膜屏障产生不利影响。15MPG不具有这种潜在有害特性，作为一种具有治疗前景的胃酸分泌抑制剂，仍值得进一步研究。