Antiulcer activity of the calcium antagonist propyl-methylenedioxyindene--V. Localization of site of action.
1. Propyl-methylenedioxyindene (pr-MDI) is an intracellular calcium antagonist which inhibits cold-restraint stress ulceration at subcardiovascular doses (less than or equal to 30 mg/kg). It also inhibits gastric acid secretion evoked by RX77368 (a stable analog of thyrotropin-releasing hormone, the putative mediator of cold-restraint stress ulcers). 2. The objective of this investigation was to localize the site of the inhibitory effect of pr-MDI on gastric acid secretion stimulated by intracisternal (i.c.) administration of RX77368 (100 ng) in rats. 3. Peripheral administration of pr-MDI (30 mg/kg i.p. or i.v.) inhibited the elevated basal and the RX 77368-induced acid secretion in conscious 2-hr pylorus-ligated rats. This effect was completely blocked in anesthetized (urethane or pentobarbital) acute gastric fistula rats. 4. Intracisternal administration of pr-MDI (0.1-1 mumol) produced a dose-related inhibition of acid secretion in conscious pylorus-ligated rats. However, urethane anesthesia completely blocked the inhibitory effect of i.c.-administered pr-MDI (1 mumol) on RX77368-induced acid secretion. 5. Since previous studies indicate that anesthesia does not inhibit peripheral actions of pr-MDI (e.g. the antiarrhythmic effect), the convergent evidence suggests that the inhibitory effect of pr-MDI on gastric acid secretion is mediated primarily via the central nervous system.
Stephens
R L
RL
Department of Physiology, College of Medicine, Ohio State University, Columbus 43210.
Rahwan
R G
RG
D000818:Animals; D000897:Anti-Ulcer Agents / Q000494:pharmacology*; D002121:Calcium Channel Blockers / Q000494:pharmacology*; D002946:Cisterna Magna; D003080:Cold Temperature; D005744:Gastric Acid / Q000378:metabolism; D066298:In Vitro Techniques; D007267:Injections; D008297:Male; D011708:Pylorus / Q000502:physiology; D011761:Pyrrolidonecarboxylic Acid / Q000031:analogs & derivatives; D051381:Rats; D011919:Rats, Inbred Strains; D013973:Thyrotropin-Releasing Hormone / Q000031:analogs & derivatives / Q000494:pharmacology
D000897:Anti-Ulcer Agents; D002121:Calcium Channel Blockers; D013973:Thyrotropin-Releasing Hormone; C027979:L-pyroglutamyl-L-histidyl-3,3-dimethylprolinamide; D011761:Pyrrolidonecarboxylic Acid