The role of gastric histamine release in the acid secretory response to pentagastrin and methacholine in the dog.
The role of gastric histamine release in the acid secretory response to pentagastrin and methacholine in the dog.
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胃组胺释放在狗对五肽胃泌素和醋甲胆碱的酸分泌反应中的作用。
DOI：
10.1007/bf01796263
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发表时间：
1995
期刊：
影响因子：
--
通讯作者：
Payne,NA
中科院分区：
文献类型：
--
作者：
Gerber,JG;Payne,NA
我们之前已经证明，在向胃脾动脉短期施用促分泌剂期间，五肽胃泌素和醋甲胆碱都可以刺激犬胃释放组胺。在这项研究中，我们测试了这样的假设：胃组胺的释放决定了对促酸分泌剂的酸分泌反应。将增加剂量的五肽胃泌素（2、6 和 20 ng/kg/min）和醋甲胆碱（0.1、0.3 和 1 µg/min）注入狗的胃脾动脉，同时监测胃酸排出量、组胺和 Nτ-甲基组胺分泌率。使用 GC/NICI-MS 测量血浆中的组胺和 Nτ-甲基组胺浓度。增加五肽胃泌素剂量导致胃排出量增加。以组胺和 Nτ-甲基组胺分泌率之和表示的总组胺分泌率显示，在两种最高剂量的五肽胃泌素的情况下，总组胺分泌率显着高于基础值。将五肽胃泌素剂量与胃酸排出量相关的回归分析给出的相关系数为0.586，非常显着。将总组胺分泌率与酸排出量相关的回归分析给出的相关系数为0.498，这也是非常显着的。乙酰甲胆碱剂量的增加也导致酸排出量呈剂量依赖性增加。仅在 1μg/min 输注速率下，组胺分泌率显示出统计学上显着高于基础的显着增加，然而，总组胺分泌率（组胺 + Nτ-甲基组胺）在乙酰甲胆碱的任何剂量下不再显着。将乙酰甲胆碱剂量与胃酸排出量相关的回归分析得出的相关系数为0.571，显着，而将组胺分泌率与胃酸排出量相关的回归分析得出的相关系数为0.338，不显着，当总组胺分泌率与酸排出量相关时，相关系数降至0.079。六十八分钟的五肽胃泌素输注显示出组胺分泌率呈剂量依赖性、脉冲状但持续高于基础值的增加，而长期输注乙酰甲胆碱则产生平坦的、低强度的组胺刺激。这些数据表明，对于五肽胃泌素，五肽胃泌素的剂量和释放的组胺量都决定了该促分泌素的酸分泌反应，但五肽胃泌素的剂量与酸输出的相关性更强。在胆碱能刺激酸排出期间，只有乙酰甲胆碱的剂量与酸排出相关。因此，对于胆碱能刺激的胃酸输出，组胺不太可能是最终介质，但对于胃泌素来说，其对壁细胞的直接作用和释放的组胺量似乎有助于酸分泌反应。
We have previously demonstrated that both pentagastrin and methacholine can stimulate histamine release from the canine stomach during short term administration of the secretagogues into the gastrosplenic artery. In this study we tested the hypothesis that gastric histamine release determines the acid secretory response to acid secretagogues. Increasing doses of pentagastrin (2, 6, and 20 ng/kg/min) and methacholine (0.1, 0.3, and 1µg/min) were infused into the gastro-splenic artery in dogs, while gastric acid output, histamine and Nτ-methyl histamine secretory rates were monitored. Histamine and Nτ-methyl histamine concentrations in plasma were measured using GC/NICI-MS. Increasing doses of pentagastrin resulted in increasing gastric output. Total histamine secretory rate expressed as the sum of histamine and Nτ-methyl histamine secretory rate showed a significant increase above basal with the two highest doses of pentagastrin. Regression analysis correlating the dose of pentagastrin to gastric acid output gave a correlation coefficient of 0.586 which was very significant. Regression analysis correlating the total histamine secretory rate to acid output gave a correlation coefficient of 0.498 which was also very significant. Increasing doses of methacholine also resulted in a dose-dependent increase in acid output. Histamine secretory rates showed a statistically significant increase above basal only at the 1µg/min infusion rate, however, the total histamine secretory rates (histamine + Nτ-methyl histamine) were no longer significant at any of the doses of methacholine. Regression analysis correlating the dose of methacholine to gastric acid output gave a correlation coefficient of 0.571 which was significant, while correlating the histamine secretory rate to acid output gave a correlation coefficient of 0.338, not significant, which decreased to 0.079 when the total histamine secretory rates were correlated to acid output. Sixty-eight min infusions of pentagastrin demonstrated a dose-dependent, pulse-like but persistent increase in histamine secretory rate above basal, while long-term infusion of methacholine gave a flat, low-grade histamine stimulation. These data suggest that for pentagastrin, both the dose of pentagastrin and the amount of histamine released determine the acid secretory response with this secretagogue, but the dose of pentagastrin correlates more strongly with acid output. During cholinergic stimulated acid output, only the dose of methacholine correlates with acid output. Thus, for cholinergic stimulated gastric acid output, histamine is not likely to be a final mediator, but for gastrin both its direct action at the parietal cell and the amount of histamine released appear to contribute to the acid secretory response.