THE ROLE OF GASTRIC HISTAMINE-RELEASE IN THE ACID SECRETORY RESPONSE TO PENTAGASTRIN AND METHACHOLINE IN THE DOG

We have previously demonstrated that both pentagastrin and methacholin e can stimulate histamine release from the canine stomach during short term administration of the secretagogues into the gastrosplenic arter y. In this study we tested the hypothesis that gastric histamine relea se determines the acid secretory response to acid secretagogues. Incre asing 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 histami ne secretory rates were monitored. Histamine and N-tau-methyl histamin e concentrations in plasma were measured using GC/NICI-MS. Increasing doses of pentagastrin resulted in increasing gastric output. Total his tamine secretory rate expressed as the sum of histamine and N-tau-meth yl histamine secretory rate showed a significant increase above basal with the two highest doses of pentagastrin. Regression analysis correl ating the dose of pentagastrin to gastric acid output gave a correlati on coefficient of 0.586 which was very significant. Regression analysi s correlating the total histamine secretory rate to acid output gave a correlation coefficient of 0.498 which was also very significant. Inc reasing doses of methacholine also resulted in a dose-dependent increa se in acid output. Histamine secretory rates showed a statistically si gnificant increase above basal only at the 1 mu g/min infusion rate, h owever, the total histamine secretory rates (histamine+N-tau-methyl hi stamine) were no longer significant at any of the doses of methacholin e. Regression analysis correlating the dose of methacholine to gastric acid output gave a correlation coefficient of 0.571 which was signifi cant, while correlating the histamine secretory rate to acid output ga ve a correlation coefficient of 0.338, not significant, which decrease d 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 secre tory rate above basal, while long-term infusion of methacholine gave a flat, low-grade histamine stimulation. These data suggest that for pe ntagastrin, 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 outpu t. During cholinergic stimulated acid output, only the dose of methach oline correlates with acid output. Thus, for cholinergic stimulated ga stric acid output, histamine is not likely to be a final mediator, but for gastrin both its direct action at the parietal cell and the amoun t of histamine released appear to contribute to the acid secretory res ponse.