Activation of parietal cell by mercaptomethylimidazole: a novel inducer of gastric acid secretion.
Mercaptomethylimidazole (2-Mercapto-1-methylimidazole, MMI), an antithyroid drug of thionamide group, significantly activated the parietal cell for acid secretion, as evidenced by increased O2 consumption by more than 2.5-fold over the basal level. When compared, MMI-induced activation was similar to that of histamine but significantly higher than that of isobutylmethylxanthine or carbachol. Activation by MMI was not prevented by receptor blockers of the parietal cell, indicating that its effect was not mediated through the cell surface histamine-H2 receptor 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-induced activation was coupled with the H+ transport was further confirmed by significant increase in [14C]-aminopyrine uptake by MMI in rabbit gastric gland preparation. MMI-dependent activation of the parietal cell correlated well with the inhibition of the endogenous peroxidase activity. In vitro studies indicated that MMI irreversibly inactivated both peroxidase and catalase activity of the parietal cell in presence of H2O2. As inactivation of these H2O2-scavenging enzymes should increase accumulation of intracellular H2O2, the effect of latter was studied on acid secretion. H2O2 at a low concentration, stimulated acid secretion by sevenfold in isolated gastric mucosa, which was sensitive to omeprazole. It also significantly stimulated [14C]-aminopyrine uptake in gastric gland preparation. We suggest that MMI activated parietal cells to stimulate acid secretion by endogenous accumulation of H2O2 through inactivation of the peroxidase-catalase system.
Bandyopadhyay
U
U
Department of Physiology, Indian Institute of Chemical Biology, Calcutta.
Chatterjee
R
R
Chakraborty
T K
TK
Ganguly
C K
CK
Bhattacharyya
D K
DK
Banerjee
R K
RK
D000632:Aminopyrine / Q000378:metabolism; D000818:Animals; D000897:Anti-Ulcer Agents / Q000494:pharmacology; D002374:Catalase / Q000037:antagonists & inhibitors; D004791:Enzyme Inhibitors / Q000494:pharmacology; D005744:Gastric Acid / Q000378:metabolism*; D006861:Hydrogen Peroxide / Q000494:pharmacology; D007093:Imidazoles / Q000494:pharmacology*; D009853:Omeprazole / Q000494:pharmacology; D010295:Parietal Cells, Gastric / Q000187:drug effects* / Q000201:enzymology / Q000378:metabolism; D009195:Peroxidase / Q000037:antagonists & inhibitors; D011817:Rabbits; D051381:Rats
C107674:2-mercapto-1-methylimidazole; D000897:Anti-Ulcer Agents; D004791:Enzyme Inhibitors; D007093:Imidazoles; D000632:Aminopyrine; D006861:Hydrogen Peroxide; D002374:Catalase; D009195:Peroxidase; D009853:Omeprazole