The fade of gastrin-stimulated gastric acid secretion in the rat is due to depletion of releasable mucosal histamine.

The present study examines the applicability of the isolated, acid-secreting vascularly perfused rat stomach for long-term physiological and pharmacological studies. The model was used to study the fade of acid secretion during gastrin stimulation. The stomachs were stimulated by exogenous gastrin or histamine alone or in succession. Acid secretion and venous histamine concentrations were measured. Gastrin and histamine potently stimulated acid output, histamine-stimulated acid secretion was sustained for 300 min while gastrin-stimulated secretion peaked at 120 min and declined towards basal output at 300 min. Stomachs rendered tachyphylactic to gastrin could be re-stimulated by exogenous histamine. Venous histamine output during gastrin stimulation decreased in parallel to acid secretion. This, the acid-secreting, isolated vascularly perfused rat stomach can be used for physiological and pharmacological studies with histamine as stimulant for at least 300 min. The present results strongly indicate that the effect of gastrin on acid secretion is mediated by histamine, and that fade of acid secretion during stimulation with gastrin is due to depletion of releasable mucosal histamine.