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 oi the isolated. acid-sec reting 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 histam ine potently stimulated acid output. histamine-stimulated acid secreti on was sustained for 300 min while gastrin-stimulated secretion peaked at 120 min and declined towards basal output at 300 min. Stomachs ren dered tachyphylactic to gastrin could be re-stimulated by exogenous hi stamine. Venous histamine output during gastrin stimulation decreased in parallel to acid secretion. Thus. the acid-secreting, isolated vasc ularly perfused rat stomach can be used for physiological and pharmaco logical studies with histamine as stimulant for at least 300 min. The present results strongly indicate that the effect of gastrin on acid s ecretion is mediated by histamine, and that fade of acid secretion dur ing stimulation with gastrin is due to depletion of releasable mucosal histamine.