The possible role of histamine in the cortisone induced gastric acid hypersecretion of the guinea‐pig

Abstract

1. The effects of cortisone treatment combined with agents influencing histamine metabolism were studied on the free and total acid output in pylorus ligated guinea-pigs. 2. It was found that reduction in the synthesis of histamine produced by the administration of a-methylDOPA significantly inhibited the acid response to cortisone. 3. Enhancement of the oxidative deamination of histamine brought about by the administration of diamine oxidase or heparin inhibited cortisone induced acid hypersecretion significantly. 4. Inhibition of the oxidative deamination of histamine tby aminoguanidine and iproniazid resulted in a significant increase of the cortisone induced acid hypersecretory response. 5. Inhibition of the methylation of histamine by chlorpromazine or 1,4-methylhistamine inhibited the cortisone induced hypersecretory response significantly. 6. Studies with labelled histamine indicated that cortisone increases the sequestration of histamine to the stomach.It has been reported by Heisler & Kovacs (1967) that administration of cortisone to guinea-pigs resulted in a decrease in gastric histamine content, while gastric acid secretory activity was increased. The results suggested that an interrelationship between cortisone treatment, gastric histamine release and acid secretion might be the underlying sequence of events in the cortisone induced secretory process.Consequently, studies were designed to suppress the synthesis and enhance or suppress the inactivation of endogenous histamine and to test the effect of these pharmacological alterations on the cortisone induced gastric secretory response. The results presented here suggest that in the guinea-pig cortisone induced acid hypersecretion might be mediated by histamine.