Histamine H2-receptor mediated stimulation of gastric acid secretion by mercaptomethylimidazole.
Intraperitoneal administration of mercaptomethylimidazole (methimazole), a potent antithyroid drug belonging to the thionamide group, caused a significant increase in gastric secretion both in control and pylorus-ligated mice. The drug also induced significant stimulation of gastric acid and pepsinogen secretion in both the animal systems studied. The dose-response curve indicated a nearly 10-fold increase in acid output by injection of 0.55 mg mercaptomethylimidazole per 25 g body weight. The duration profile of the drug response at the dose mentioned showed acid secretion almost at a linear rate up to 2.5 hr, after which the response decreased to some extent. Of the other antithyroid drugs of the same family, only thiourea activated acid secretion but the response was much smaller than mercaptomethylimidazole. Histamine, one of the physiological secretagogues of gastric acid secretion, was found to be less active than mercaptomethylimidazole. Mercaptomethylimidazole-induced stimulation of acid secretion could be effectively blocked by prior administration of cimetidine and completely by omeprazole and not by atropine. Verapamil and nifedipine had also some inhibitory effect. These observations indicate that mercaptomethylimidazole stimulates HCl secretion through the involvement of H2-receptor and through the functioning of the H+-K+-ATPase of the parietal cells. The bulk movement of water during increased HCl secretion was partially sensitive to cimetidine and omeprazole and was also associated with an increased secretion of Na+ and K+ in the gastric juice. This indicates that mercaptomethylimidazole also induced water transport through a separate mechanism.
Bhattacharjee
M
M
Department of Physiology, Indian Institute of Chemical Biology, Calcutta.
Bose
A K
AK
Banerjee
R K
RK
D000818:Animals; D002927:Cimetidine / Q000494:pharmacology; D005744:Gastric Acid / Q000378:metabolism*; D008297:Male; D008713:Methimazole / Q000037:antagonists & inhibitors / Q000494:pharmacology*; D051379:Mice; D008807:Mice, Inbred BALB C; D009543:Nifedipine / Q000494:pharmacology; D009853:Omeprazole / Q000494:pharmacology; D010295:Parietal Cells, Gastric / Q000187:drug effects; D011188:Potassium / Q000378:metabolism; D006180:Proton-Translocating ATPases / Q000378:metabolism; D011708:Pylorus / Q000187:drug effects; D011970:Receptors, Histamine H2 / Q000187:drug effects* / Q000502:physiology; D012964:Sodium / Q000378:metabolism; D014700:Verapamil / Q000494:pharmacology
D011970:Receptors, Histamine H2; D008713:Methimazole; D002927:Cimetidine; D012964:Sodium; D014700:Verapamil; D006180:Proton-Translocating ATPases; D009543:Nifedipine; D009853:Omeprazole; D011188:Potassium