Taylor S D, Chey W Y, Scheiman J M
Division of Gastroenterology, University of Michigan, Ann Arbor, USA.
J Clin Gastroenterol. 1995 Mar;20(2):131-5. doi: 10.1097/00004836-199503000-00012.
Secretin is an important physiologic regulator of gastric acid and pancreatic bicarbonate secretion. Endogenous prostaglandins play an important intermediary role, because indomethacin pretreatment prevents the physiological actions of secretin. Misoprostol is a prostaglandin E1 (PGE1) analog used for the prevention of nonsteroidal antiinflammatory drug (NSAID)-induced ulceration. This study sought to determine whether cotherapy with misoprostol reverses the NSAID-induced blockade of secretin's inhibition of human gastric acid secretion. Seven healthy volunteers were studied. Gastric acid secretion was measured during the basal, pentagastin-stimulated and intravenous secretin--inhibited states. The studies were then repeated after 3 days of oral indomethacin (50 mg p.o. t.i.d. for 10 doses) with and without concomitant misoprostol (200 micrograms q.i.d. for 13 doses). Exogenous secretin reduced pentagastrin-stimulated acid secretion by 35%, and this inhibition was reduced to 9% during indomethacin treatment (p < 0.05). Cotherapy with misoprostol during indomethacin treatment did not restore secretin's inhibition of gastric acid secretion; paradoxically, during secretin administration, acid secretion increased. When subjects received misoprostol treatment only, secretin failed to inhibit gastric acid secretion. We conclude that during indomethacin treatment, cotherapy with misoprostol cannot restore the inhibitory action of secretin to inhibit gastric acid secretion. These results suggest that PGE1 is an unlikely intermediate in secretin's physiological action. Although misoprostol can prevent NSAID-induced ulcers, it does not ameliorate all physiological perturbations induced by cyclooxygenase inhibition.
促胰液素是胃酸和胰腺碳酸氢盐分泌的重要生理调节因子。内源性前列腺素起重要的中介作用，因为吲哚美辛预处理可阻止促胰液素的生理作用。米索前列醇是一种前列腺素E1（PGE1）类似物，用于预防非甾体抗炎药（NSAID）引起的溃疡。本研究旨在确定米索前列醇联合治疗是否能逆转NSAID引起的促胰液素对人胃酸分泌抑制作用的阻断。研究了7名健康志愿者。在基础状态、五肽胃泌素刺激状态和静脉注射促胰液素抑制状态下测量胃酸分泌。然后在口服吲哚美辛（50mg口服，每日3次，共10剂）3天后，分别在同时服用和不服用米索前列醇（200μg每日4次，共13剂）的情况下重复这些研究。外源性促胰液素使五肽胃泌素刺激的胃酸分泌减少35%，在吲哚美辛治疗期间这种抑制作用降至9%（p<0.05）。吲哚美辛治疗期间与米索前列醇联合治疗并未恢复促胰液素对胃酸分泌的抑制作用；矛盾的是，在给予促胰液素期间，胃酸分泌增加。当受试者仅接受米索前列醇治疗时，促胰液素未能抑制胃酸分泌。我们得出结论，在吲哚美辛治疗期间，与米索前列醇联合治疗不能恢复促胰液素抑制胃酸分泌的作用。这些结果表明，PGE1不太可能是促胰液素生理作用的中介物。虽然米索前列醇可以预防NSAID引起的溃疡，但它并不能改善环氧化酶抑制引起的所有生理紊乱。
