Metabolism of histamine in secreting and isolated canine stomach

Abstract

Total 14C activity in juice secreted by gastric pouches of six dogs and seven isolated canine stomachs was determined in response to intravenous and intra-arterial infusions of histamine and [14C]histamine. The proportions of 14C attributable to histamine, Nalpha-methylhistamine (NalphaMeH), Nalpha,Nalpha-dimethylhistamine (NalphaNalphaMe2H), N-telle-methylhistamine (NtauMeH), imidazole acetic acid (ImAA), N-methylimidazole acetic acid (NtauMeImAA), acetylhistamine (AcH), and histaminol (HOH) were defined using thin-layer chromatography. Similar estimates were made at the end of infusions on blood, gastric mucosa, and gastric muscle. Methylation was the major, or sole, route of metabolism of histamine in the gastric mucosa, and the major product was inactive NtauMeH. Small quantities of the active NalphaMe derivatives, particularly NalphaNalphaMe2H, were identified in both the juice and mucosa. Little or no ImAA, NtauMeImAA, AcH, and HOH were present in juice from isolated stomachs while they did occur in the juice from intact dogs, demonstrating they are extragastric metabolites of histamine. A major mucosal function of methylation of histamine is inactivation, although NalphaMe derivatives formed may play a role in the secretagogue action of histamine.