Intravenous infusion of L-isomers of phenylalanine and tryptophan stimulate gastric acid secretion at physiologic plasma concentrations in normal subjects and after parietal cell vagotomy.

To determine whether intravenous infusion of individual amino acids stimulated gastric acid secretion in man, graded doses of phenylalanine, tryptophan, glycine, alanine, histidine, and NaCl control were infused on separate days in nine healthy subjects. Intravenous infusion of phenylalanine and tryptophan significantly stimulated gastric acid secretion to 50 and 52%, respectively, of the acid secretory response to intragastric peptone. Intravenous alanine and histidine were without effect, whereas glycine produced a slight response. Serum gastrin concentrations did not significantly change during intravenous amino acid infusion, except in response to 0.1 M phenylalanine. However, the increase in serum gastrin occurred 2 h after acid secretion had significantly increased in response to the 0.025 M phenylalanine infusion. Plasma amino acid concentrations were measured during intravenous amino acid infusion and in response to a steak meal in five of the subjects. At a time when acid secretion was significantly increased during intravenous infusion of phenylalanine and tryptophan, plasma amino acids were similar to, or less than, that observed after the steak meal, suggesting that circulating levels of these three amino acids have a physiologic effect on gastric secretion in man. Intravenous infusion of a combination of graded doses of phenylalanine plus a continuous infusion of 0.01 M tryptophan shifted the dose-response curve to the left and resulted in a significantly greater response than to either amino acid alone. In five subjects with parietal cell vagotomy, intravenous phenylalanine and tryptophan stimulated acid secretion, whereas histidine was without effect, similar to normal subjects. These studies indicate that intravenous infusion of small amounts of phenylalanine (0.025 M, 3.1 mmol/h) and tryptophan (0.01 M, 1.25 mmol/h) stimulated gastric acid secretion at plasma concentrations similar to those observed after a steak meal, suggesting a physiologic role for circulating levels of these amino acids on gastric acid secretion. Because acid secretion increased at a time when serum gastrin was unchanged and since there was no correlation between changes in serum gastrin and acid secretion, the responses to phenylalanine and tryptophan are probably mediated by a nongastrin-related mechanism(s). Since both phenylalanine and tryptophan stimulated secretion in vagotomized subjects, the response is vagally independent. These observations suggest that circulating levels of these two amino acids have either a direct or indirect effect on or near the human parietal cell.