Production of N-alpha-methyl-histamine, which is a histamine 3 receptor (H3R) agonist, is promoted in Helicobacter pylori infected human gastric mucosa. NAMH acts directly on H2Rs in animals to stimulate acid secretion and to be a H2R agonist. NAMH dose dependently stimulated cAMP productions in CHO-H2R cells. This production was inhibited by famotidine but not by thioperamide. Control CHO cells were unresponsive to either histamine or NAMH. In addition, the effect of NAMH, in terms of cAMP production in CHO-H2R cells, was more potent than that of histamine-that is, with a lower EC50 concentration and higher maximal cAMP production. Both NAMH and histamine, but not R-alpha-methyl-histamine, effectively inhibited [(3)H] tiotidine binding to CHO-H2R cells. These results confirm that NAMH, which is produced in the gastric mucosa by H pylori, is a potent H2R agonist as well as a H3R agonist.
