Inhibition of Gastric Acid Secretion in Man by Exogenous and Endogenous Pancreatic Glucagon

The interaction of intravenously infused glucagon and pentagastrin on gastric acid secretion was studied in 5 healthy subjects. First a step dose-response study with pentagastrin in doses of 0.01, 0.1,1.0, and 10.0 mug per kg-hr was performed. The dose required for one-half maximal response (D50) was 130 ng per kg-hr. With this dose of pentagastrin as background stimulation a step dose-response study with glucagon in doses of 0.5, 2.0, 8.0, and 16.0 mug per kg-hr was performed. The dose of glucagon required for one-half maximal inhibition was 1.64 mug per kg-hr. In a third experiment the dose-response study with pentagastrin was repeated on a background infusion of glucagon in the dose found to be D50. A significant inhibition of acid secretion was found on all dose levels. The inhibition followed noncompetitive kinetics. Plasma concentrations of pancreatic glucagon in 4 of the 5 subjects in this experiment were comparable concentrations seen after a protein meal. Intravenous infusion of l-arginine on a background stimulation of acid secretion with synthetic human gastrin I in a dose of 250 ng per kg-hr was performed in 7 healthy subjects. Arginine increased serum glucagon concentration to levels seen after a meal and resulted in a significant inhibition of acid secretion. The results favor the hypothesis that pancreatic glucagon may participate in the physiological inhibition of gastric acid secretion.