Effect of N-alpha-methyl-histamine on acid secretion in isolated cultured rabbit parietal cells: Implications for Helicobacter pylori associated gastritis and gastric physiology

Background-Helicobacter pylori has been shown to produce the unusual metabolite N-alpha-methyl-histamine. This compound is known to be a potent agonist at inhibitory histamine H-3 receptors. There is increasing evidence implicating this receptor in the control of gastric acid secretion but the mechanism for this remains to be clarified. Aims-To investigate the effect of N-alpha-methyl-histamine on the acid secretory activity of parietal cells and to determine the mechanism for such effects, thus helping to determine the role of this compound in the pathophysiology of H pylori infection. Methods-Rabbit parietal cells were isolated and enriched by collagenase-EDTA digestion and centrifugal elutriation. Following culture on Matrigel coated plates, acid secretion was assessed by C-14 aminopyrine accumulation. Results-N-alpha-methyl-histamine (100 mu M) was as potent as histamine (100 mu M) in stimulating acid secretion. This effect was reversed by ranitidine indicating it was mediated via the H-2 receptor. N-alpha-methylhistamine potentiated the effects of both carbachol (increased by 280%) and gastrin (by 350%) (p<0.01). N-alpha-methyl-histamine had no inhibitory actions on forskolin or carbachol stimulated acid secretion suggesting that there is not an inhibitory H-3 receptor located directly on the parietal cell. Conclusions-Bacterially produced N-alpha-methyl-histamine directly stimulates acid secretion by parietal cells and this may contribute to the increased acid secretion that contributes to duodenal ulceration.