Gerber J G, Payne N A, Fadul S, Nies A S
Eur J Pharmacol. 1984 Nov 13;106(2):373-80. doi: 10.1016/0014-2999(84)90725-8.
The effect of cholinergic stimulation on gastric acid secretion was examined in mongrel dogs using an in vivo and an in vitro preparation for comparison. The gastric fistula dog was used for the in vivo studies, and methacholine was infused directly into the artery supplying the fundus of the stomach to avoid systemic hemodynamic changes. Isolated parietal cells were used for the in vitro studies. In vivo, methacholine infused at 1 microgram/min was found to stimulate gastric acid secretion that was inhibited 98.5 +/- 1.4% by intravenously administered metiamide (H2 blocker) and 72 +/- 11% by intra-arterially administered glucagon. Glucagon had no effect on histamine stimulated acid secretion. In vitro, increasing concentrations of methacholine from 10(-7), 10(-6) to 10(-5) M stimulated [14C]aminopyrine uptake into parietal cells in a concentration dependent manner. This effect of methacholine was unaltered by 10(-4) M metiamide or 10(-6) M glucagon. However, atropine 10(-5) M totally blocked the stimulatory effect of methacholine. Our data suggest that the cholinergic mechanism of acid secretion is different when examined in vivo vs. in vitro even in the same species. In vivo histamine dependency has a major contribution to the cholinergic mechanism of acid secretion, whereas in vitro the interaction of the cholinergic agonist at the muscarinic receptor results in acid stimulation that does not require the presence of histamine.
为进行比较，使用体内和体外制备方法研究了胆碱能刺激对杂种犬胃酸分泌的影响。体内研究使用胃瘘犬，将乙酰甲胆碱直接注入供应胃底的动脉，以避免全身血流动力学变化。体外研究使用分离的壁细胞。在体内，发现以1微克/分钟的速度注入乙酰甲胆碱可刺激胃酸分泌，静脉注射甲硫咪特（H2受体阻滞剂）可抑制98.5±1.4%的胃酸分泌，动脉注射胰高血糖素可抑制72±11%的胃酸分泌。胰高血糖素对组胺刺激的胃酸分泌无影响。在体外，乙酰甲胆碱浓度从10^(-7)、10^(-6)增加到10^(-5)M时，以浓度依赖的方式刺激壁细胞摄取[14C]氨基比林。10^(-4)M甲硫咪特或10^(-6)M胰高血糖素不会改变乙酰甲胆碱的这种作用。然而，10^(-5)M阿托品完全阻断了乙酰甲胆碱的刺激作用。我们的数据表明，即使在同一物种中，体内和体外研究时胃酸分泌的胆碱能机制也有所不同。在体内，组胺依赖性对胃酸分泌的胆碱能机制有主要贡献，而在体外，胆碱能激动剂与毒蕈碱受体的相互作用导致胃酸刺激，且不需要组胺的存在。
