哇巴因抑制Na⁺,K⁺-ATP酶对小鼠离体胃组胺和氨甲酰甲胆碱酸分泌反应的不同影响
Differential effects of Na+, K(+)-ATPase inhibition by ouabain on acid secretory responses to histamine and bethanechol in the mouse isolated stomach.
作者信息
Horie S, Yano S, Watanabe K
机构信息
Department of Drug Evaluation and Toxicological Sciences, Faculty of Pharmaceutical Sciences, Chiba University, Japan.
出版信息
Br J Pharmacol. 1994 May;112(1):87-92. doi: 10.1111/j.1476-5381.1994.tb13034.x.
Abstract
- The effect of Na+,K(+)-ATPase inhibition by ouabain on gastric acid secretion was studied in the mouse isolated whole stomach preparation. 2. Ouabain caused a transient enhancement of histamine-induced gastric acid secretion followed by an inhibitory phase. On the other hand, ouabain caused a rapid reduction of bethanechol-stimulated acid secretion without an enhancement phase. 3. In dibutyryl cyclic AMP-induced acid secretion, ouabain led to a transient increase in acid secretion followed by a fall, as was seen with the histamine stimulation. Ouabain caused a rapid reduction of A23187-induced acid secretion. 4. Ouabain by itself increased basal acid secretion, and thereafter slowly suppressed the acid secretion. 5. Atropine inhibited both the ouabain-induced enhancement of the stimulated gastric acid secretion and the ouabain-induced stimulation of basal acid secretion. 6. The present study showed that Na+,K(+)-ATPase inhibition by ouabain caused a phasic enhancement of the stimulated gastric acid secretion through release of endogenous acetylcholine when the secretagogues act via an intracellular cyclic AMP pathway. It also inhibited the stimulated acid secretion irrespective of secretagogues, probably through its inhibitory effect on Na+,K(+)-ATPase in the gastric parietal cell.
摘要
- 在小鼠离体全胃标本中研究了哇巴因抑制Na⁺,K⁺-ATP酶对胃酸分泌的影响。2. 哇巴因引起组胺诱导的胃酸分泌短暂增强，随后进入抑制阶段。另一方面，哇巴因使氨甲酰甲胆碱刺激的胃酸分泌迅速减少，无增强阶段。3. 在二丁酰环磷腺苷诱导的胃酸分泌中，哇巴因导致胃酸分泌短暂增加，随后下降，这与组胺刺激时所见相同。哇巴因使A23187诱导的胃酸分泌迅速减少。4. 哇巴因本身增加基础胃酸分泌，此后缓慢抑制胃酸分泌。5. 阿托品抑制哇巴因诱导的刺激胃酸分泌增强以及哇巴因诱导的基础胃酸分泌刺激。6. 本研究表明，当促分泌剂通过细胞内环磷腺苷途径起作用时，哇巴因抑制Na⁺,K⁺-ATP酶通过释放内源性乙酰胆碱引起刺激胃酸分泌的阶段性增强。它也抑制刺激的胃酸分泌，而与促分泌剂无关，可能是通过其对胃壁细胞中Na⁺,K⁺-ATP酶的抑制作用。
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