Im W B, Blakeman D P, Sachs G
Biochim Biophys Acta. 1985 Apr 22;845(1):54-9. doi: 10.1016/0167-4889(85)90054-0.
We have examined the interaction of omeprazole, a gastric antisecretory agent, with endogenous or exogenous sulfhydryl compounds in isolated rabbit gastric glands. The glands exposed to omeprazole (2 microM for 50 min) could recover acid secretory response to dibutyryl-cAMP upon addition of dithiothreitol, cysteine or glutathione. Washing the omeprazole-exposed glands free of the extracellular drug also led to a similar recovery of the acid secretory response. Depletion of cellular glutathione with 2-cyclohexen-1-one had no considerable effect on the secretory response of the glands to dibutyryl-cAMP, but prevented the reversal of the antisecretory effect of omeprazole upon washing or adding exogenous cysteine. Also, the antisecretory potency of omeprazole increased several fold in the glutathione-depleted glands. These observations indicate that cellular glutathione is essential to reactivate the omeprazole-modified enzyme(s), possibly (H+ + K+)-ATPase, in acid secretory process and led us to propose that omeprazole is an agent reacting with sulfhydryl groups.
我们研究了胃分泌抑制剂奥美拉唑与分离的兔胃腺中内源性或外源性巯基化合物的相互作用。暴露于奥美拉唑（2微摩尔，50分钟）的胃腺在加入二硫苏糖醇、半胱氨酸或谷胱甘肽后，对二丁酰环磷腺苷酸的酸分泌反应能够恢复。将暴露于奥美拉唑的胃腺冲洗以去除细胞外药物，也会导致酸分泌反应出现类似的恢复。用2-环己烯-1-酮消耗细胞内谷胱甘肽对胃腺对二丁酰环磷腺苷酸的分泌反应没有显著影响，但阻止了奥美拉唑的抗分泌作用在冲洗或添加外源性半胱氨酸后逆转。此外，在谷胱甘肽耗尽的胃腺中，奥美拉唑的抗分泌效力增加了几倍。这些观察结果表明，细胞内谷胱甘肽对于在酸分泌过程中重新激活可能被奥美拉唑修饰的酶（可能是（H⁺+K⁺）-ATP酶）至关重要，并使我们提出奥美拉唑是一种与巯基反应的药物。
