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.
