Mucosal histamine elimination and its effect on acid secretion in rabbit gastric mucosa

Rapid elimination of histamine near the oxyntic cells is important in the termination of the secretory response when the signal for histamine release is discontinued. The mechanism of this local process is still unclear.

Gastric mucosal histamine elimination was, therefore, examined in fundic mucosa mounted in flux chambers and in dispersed mucosal cells.

[3H]histamine placed into the serosal chamber medium was transported across the mucosal tissue into the lumen, but a greater quantity was methylated to an inactive metabolite, Nt-methylhistamine, and preferentially released to the serosal chamber, the interstitial medium. Both processes were enhanced by increased substrate concentration. They were reduced by lowering the temperature and by sodium replacement. Inhibition of histamine methyltransferase suppressed histamine uptake and methylation and significantly increased histamine-stimulated acid secretion in the tissue preparation and in dispersed mucosal cells. The augmentation was reduced by an H2-receptor blocker.

Mucosal histamine methylation and the secretion of histamine into the gastric lumen removes histamine from the extracellular space effectively, reducing the histamine concentration near the oxyntic cell surface.