Effect of histamine and cimetidine on amino acid meal-stimulated gastrin release at a controlled intragastric pH in healthy human beings.

Results of several experiments have suggested that histamine-2 receptors play an inhibitory role in regulating gastrin release. We evaluated this prospectively in healthy human beings by infusing intravenously either histamine (0.33 micrograms/kg/min) or cimetidine (3.33 mg/min) during a continuous 3-h intragastric infusion of a 3% mixed amino acid meal, a potent stimulus of gastrin release. In order to be certain that effects of histamine or cimetidine on gastrin release were independent of their known effects on gastric acid secretion, intragastric pH was maintained at 5.0 by in vivo intragastric titration with sodium bicarbonate or hydrochloric acid. Although histamine and cimetidine had significant effects on gastric acid secretion, neither significantly affected the rises in serum gastrin concentrations during intragastric amino acid infusion. For example, mean gastrin rises above basal concentrations were 39 +/- 9 pg/ml on the control day, 39 +/- 9 pg/ml on the histamine day and 44 +/- 11 pg/ml on the cimetidine day (P greater than 0.05). Thus, blockade or stimulation of H2-receptors at the doses tested had no effect on gastrin release in response to an amino acid meal in humans when intragastric pH was maintained at 5.0.