ACTIVATION OF PARIETAL-CELL BY MERCAPTOMETHYLIMIDAZOLE - A NOVEL INDUCER OF GASTRIC-ACID SECRETION

Mercaptomethylimidazole (2-Mercapto-1-methylimidazole, MMI), an antith yroid drug of thionamide group, significantly activated the parietal c ell for acid secretion, as evidenced by increased O-2 consumption by m ore than 2.5-fold over the basal level. When compared, MMI-induced act ivation was similar to that of histamine but significantly higher than that of isobutylmethylxanthine or carbachol. Activation by MMI was no t prevented by receptor blockers of the parietal cell, indicating that its effect was not mediated through the cell surface histamine-H-2 re ceptor or the muscarinic receptor. However, the activation was almost completely blocked only by omeprazole, an established inhibitor of the terminal proton-pumping H+-K+-ATPase of the parietal cell. That MMI-i nduced activation was coupled with the H+ transport was further confir med by significant increase in [C-14]-aminopyrine uptake by MMI in rab bit gastric gland preparation. MMI dependent activation of the parieta l cell correlated well with the inhibition of the endogenous peroxidas e activity. In vitro studies indicated that MMI irreversibly inactivat ed both peroxidase and catalase activity of the parietal cell in prese nce of H2O2. As inactivation of these H2O2-scavenging enzymes should i ncrease accumulation of intracellular H2O2, the effect of latter was s tudied on acid secretion. H2O2 at a low concentration, stimulated acid secretion by sevenfold in isolated gastric mucosa, which was sensitiv e to omeprazole. It also significantly stimulated [C-14]-aminopyrine u ptake in gastric gland preparation. We suggest that MMI activated pari etal cells to stimulate acid secretion by endogenous accumulation of H 2O2 through inactivation of the peroxidase-catalase system. (C) 1997 E lsevier Science Inc.