Detection and possible role of a chain methylated histamine metabolite(s) in guinea-pig stomach

Abstract

Biologically active chain-methylated histamine analogues, N-methylhistamine and N,N-dimethylhistamine have been confirmed to exert a marked gastric acid secretory effect: 0.17 mg/kg of each produced a higher acid output in pylorus ligated guinea-pigs than 0.4 mg/kg of histamine. A chain-methylated histamine metabolite(s) hitherto described only in human urine, was detected in the stomachs of guinea-pigs pretreated with cortisone. Inhibition of the oxidative deamination of endogenous histamine by aminoguanidine also led to the detection of this substance(s) in guinea-pig stomachs. If, however, the methylation of histamine was inhibited by the aministration of chlorpromazine, the cortisone induced formation of chain-methylated metabolites was inhibited. In studies with labelled histamine cortisone was shown to decrease the ratio of 14C-histamine: total 14C-methylhistamine indicating that methylation occured to a greater extent in the stomachs of cortisone pretreated guinea-pigs than in the stomachs of control animals. It is suggested that cortisone treatment might increase the formation of a chain-methylated metabolite(s) by enhancing the activity of the methylating enzyme system and that the gastric acid hypersecretory effect of cortisone in guinea-pigs may be due at least in part to the increased formation of this active histamine metabolite(s).