Dissociation of gastric acid and pepsinogen secretion in response to mercaptomethylimidazole--a new secretory compound.
Mercaptomethylimidazole (MMI), a potent antithyroid drug of the thionamide group, induces both acid and pepsinogen secretion independently in control and pylorus ligated mice. The effect is dose dependent and the drug is more effective than histamine, carbachol or isoproterenol when administered by an intraperitoneal route. MMI-stimulated pepsinogen secretion could be dissociated from the acid secretion by the use of cimetidine and omeprazole which effectively block the acid secretion without affecting the pepsinogen output. Neither acid nor pepsinogen secretion by MMI is inhibited by atropine indicating a lack of muscarinic receptor involvement in both of the processes. Nifedipine and verapamil, the calcium antagonists, by inhibiting the MMI-induced acid secretion can also dissociate pepsinogen secretion from the acid secretion. Clonidine, an alpha 2-agonist, and hexobarbital, a membrane active barbiturate, also inhibit acid secretion without affecting the pepsinogen output. These data indicate that MMI induces pepsinogen secretion independent of acid secretion. Furthermore, MMI-stimulated acid secretion is not additive with that of the histamine indicating same site (H2-receptor) of action while its synergistic effect in presence of carbachol (muscarinic receptor) indicates different site of interaction of the two compounds. On the other hand, an additive effect of MMI and carbachol on pepsinogen secretion indicates that while the carbachol effect is mediated through the muscarinic receptor, MMI stimulates pepsinogen secretion through some still unknown mechanism.
Bhattacharjee
M
M
Department of Physiology, Indian Institute of Chemical Biology, Calcutta.
Chakraborty
T
T
Banerjee
R K
RK
D000818:Animals; D013956:Antithyroid Agents / Q000494:pharmacology*; D002217:Carbachol / Q000494:pharmacology; D005744:Gastric Acid / Q000378:metabolism*; D006632:Histamine / Q000494:pharmacology; D007274:Injections, Intraperitoneal; D007545:Isoproterenol / Q000494:pharmacology; D008026:Ligation; D008297:Male; D008713:Methimazole / Q000494:pharmacology*; D051379:Mice; D008807:Mice, Inbred BALB C; D010434:Pepsin A / Q000378:metabolism; D010435:Pepsinogens / Q000378:metabolism*; D011708:Pylorus / Q000187:drug effects* / Q000378:metabolism
D013956:Antithyroid Agents; D010435:Pepsinogens; D008713:Methimazole; D006632:Histamine; D002217:Carbachol; D010434:Pepsin A; D007545:Isoproterenol