The metabolism of [14C]histamine during pentagastrin-stimulated acid secretion in the cat.

1. The metabolism of exogenous [14C]histamine has been examined in cats during gastric secretion. The appearance of 14C-labelled metabolites has been measured chromatographically in urine and gastric juice under non-secreting and pentagastrin-stimulated conditions, and in gastric mucosa after pentagastrin stimulation. 2. The main metabolites detected were (i) an acidic product, presumed to be methylimidazoleacetic acid, (ii) Ntau-methylhistamine, and (iii) an unidentified metabolite, moving rapidly in the chromatographic systems used, and designated 'preacetylhistamine'. No evidence was found for the presence of side chain (i.e. Nalpha)-methylated histamines, either in the non-stimulated or pentagastric-stimulated state. 3. During a 3 hr non-stimulated period, followed by 3 hr of pentagastrin administration, the relative proportions of 14C-labelled metabolites excreted in urine remained unchanged. During acid secretion there was an increase in the proportion of 'pre-acetylhistamine' in gastric juice, which occurred at the expense of the acidic metabolites. It is suggested however that this effect is more likely to be the result of a slow adaptation to the administration of exogenous [14C]histamine than the result of acid secretion. 4. The results of the present work do not appear to support the hypothesis of Code (1970), that a local control mechanism for acid secretion might involve the formation Nalpha-methylated histamine metabolites in gastric mucosa.