Uptake, disposition and metabolism of histamine in isolated heart preparations.

1. The uptake and metabolism of histamine by the guinea-pig heart and by the isolated electrically driven guinea-pig left atria was studied with both labelled and unlabelled histamine.2. Histamine uptake took place against a concentration gradient and, at low concentrations, this was blocked by hypoxia plus glucose deprivation or by a toxic dose of ouabain.3. The histamine taken up was retained by cardiac tissues and mainly metabolized into methyl-histamine and other metabolites. The uptake and metabolism of histamine was higher in atria than in ventricles thus reflecting the regional distribution of endogenous histamine and mast cell numbers.4. The uptake and metabolism of histamine were greatly reduced in hearts which had been depleted of mast cells, by combining cardiac anaphylaxis and (+)-tubocurarine (1 mg/ml), but pretreatment of guinea-pigs with 6-hydroxy-dopamine failed to affect uptake of total radioactivity in the isolated left atria.5. In the guinea-pig heart histamine appears to be taken up, stored and metabolized in at least two pools, one of which is linked to the mast cells.