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 m etabolite N-alpha-methyl-histamine. This compound is known to be a pot ent agonist at inhibitory histamine H-3 receptors. There is increasing evidence implicating this receptor in the control of gastric acid sec retion but the mechanism for this remains to be clarified. Aims-To inv estigate the effect of N-alpha-methyl-histamine on the acid secretory activity of parietal cells and to determine the mechanism for such eff ects, thus helping to determine the role of this compound in the patho physiology of H pylori infection. Methods-Rabbit parietal cells were i solated and enriched by collagenase-EDTA digestion and centrifugal elu triation. 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 stimulat ing acid secretion. This effect was reversed by ranitidine indicating it was mediated via the H-2 receptor. N-alpha-methylhistamine potentia ted 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 ce ll. Conclusions-Bacterially produced N-alpha-methyl-histamine directly stimulates acid secretion by parietal cells and this may contribute t o the increased acid secretion that contributes to duodenal ulceration .