The role of gastric histamine release in the acid secretory response to pentagastrin and methacholine in the dog
Gerber, J.G.; Payne, N.A.
Inflammation Research Official Journal of the European Histamine Research Society . 44(8): 327-334
ISSN/ISBN: 1023-3830 PMID: 8581519 DOI: 10.1007/bf01796263
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 1 mu-g/min) were infused into the gastrosplenic artery in dogs, while gastric acid output, histamine and N-tau-methyl histamine secretory rates were monitored. Histamine and N-tau-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 N-tau-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 1 mu-g/min infusion rate, however, the total histamine secretory rates (histamine + N-tau-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.