Effect of Histaminase Inhibitors on Gastric Secretion

Abstract

1-Isonicotinyl-2-isopropylhydrazine, ‘Marsilid,’ and isonicotinylhydrazine, ‘Rimifon,’ stimulate gastric secretion in a Heidenhain and Ivy transplanted pouch dog when given intravenously during the fasting basal state. The secretory threshold for these compounds, especially ‘Rimifon,’ is close to a toxic dose. Aminoguanidine given intravenously stimulates gastric secretion in the anesthetized dog and cat in doses which do not reduce blood pressure and do not give rise to evidences of toxicity. In the Heidenhain and Ivy transplanted pouch dog an intravenous threshold dose of aminoguanidine, an inhibitor of histaminase or histamine metabolizing enzyme I, decidedly augments the gastric secretory response to a small test-meal, even when the test-meal contains little or no histamine. Assuming on the basis of evidence published by Schayer and his colleagues (13–16) that aminoguanidine does not act directly on the parietal cell, it is concluded that histamine (or a substance inactivated by diamine oxidase) acts directly and physiologically to stimulate gastric secretion either by being released into the blood stream or by being released in the region of the parietal cell by a nonhistamine gastrin.