SUBSTITUTED BENZIMIDAZOLES INHIBIT GASTRIC-ACID SECRETION BY BLOCKING (H++K+)ATPASE
SUBSTITUTED BENZIMIDAZOLES INHIBIT GASTRIC-ACID SECRETION BY BLOCKING (H++K+)ATPASE
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DOI：
10.1038/290159a0
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发表时间：
1981-01-01
期刊：
影响因子：
64.8
通讯作者：
WALLMARK, B
中科院分区：
文献类型：
--
作者：
FELLENIUS, E;BERGLINDH, T;WALLMARK, B
体内1、2和体外1 - 5的研究均表明，取代的苯并咪唑抑制二丁酰环腺苷酸和组胺产生的酸分泌刺激。此外，与H2拮抗剂和抗胆碱能药物的结果不同，其抑制作用不是竞争性的，作用部位是双丁酰环腺苷酸的细胞内和外周。为了研究取代的苯并咪唑的生物化学作用机制，已经直接在从猪和人胃粘膜分离的（H++ K+）ATP酶上或在从兔和人胃粘膜分离的胃腺中该酶的功能上测试了一种这样的化合物H 149/94（2-{ [2-（3-甲基）吡啶基-甲基]-亚磺酰基]-5-甲氧羰基-6-甲基苯并咪唑）。（H++ K+）ATP酶6，7仅在壁细胞的分泌表面发现8，催化质子和钾离子的一对一交换9 -11。它可能是胃粘膜内的质子泵，因此可能是酸分泌过程的终端或终端步骤之一12，13。我们发现H 149/94抑制（H++ K+）ATP酶，这可能解释了它在体外和体内抑制酸分泌的作用。由于（H++ K+）ATP酶的独特分布和性质，H 149/94对该酶的抑制作用可能是抑制酸分泌过程的高度选择性临床手段。
Studies bothin vivo1,2andin vitro1–5have shown that substituted benzimidazoles inhibit the stimulation of acid secretion produced by dibutyryl cyclic AMP and histamine. Furthermore, the results differ from those produced by H2antagonists and anticholinergic agents in that the inhibition is not competitive, and the site of action is intracellular and peripheral to that of dibutyryl cyclic AMP. To investigate the biochemical mechanism of action of substituted benzimidazoles, one such compound, H 149/94 (2-{ [2-(3-methyl)pyridyl-methyl]-sulphinyl]-5-methoxycarbonyl-6-methylbenzimidazol), has been tested either directly on an (H++ K+) ATPase isolated from pig and human gastric mucosa or on the function of this enzyme in gastric glands isolated from rabbit and human gastric mucosa. (H++ K+)ATPase6,7, which has only been found at the secretory surface of the parietal cell8, catalyses a one-to-one exchange of protons and potassium ions9–11. It is possibly the proton pump within the gastric mucosa, and may thus be the terminal or one of the terminal steps of the acid secretory process12,13. We show here that H 149/94 inhibits (H++ K+)ATPase, which may explain its inhibitory action on acid secretionin vitroandin vivo. Because of the unique distribution and properties of the (H++ K+) ATPase, the inhibitory action of H 149/94 on this enzyme may be a highly selective clinical means of suppressing the acid secretory process.