Antiulcer activity of the calcium antagonist propyl-methylenedioxyindene. IV. Effects on gastric lesions in rats induced by cold-restraint stress and thyrotropin-releasing hormone.
Propyl-methylenedioxyindene (pr-MDI; 30 mg/kg, i.p.), an intracellular calcium antagonist, significantly reduced the number and size of erosions per stomach induced by cold-restraint stress by 69% and 86%, respectively. Our previous findings indicate that the antiulcer activity of pr-MDI is highly correlated with its inhibitory effect on gastric motor activity. Since central TRH is suggested as the brain mediator responsible for cold-restraint stress gastric ulcers in rats, the inhibitory action of pr-MDI was evaluated in the TRH-induced gastric lesion model. Pr-MDI (30 mg/kg) did not reduce the gastric erosions induced by intracisternal administration of 100ng RX77368, a stable thyrotropin-releasing hormone (TRH) analogue, even though it abolished the RX77368-induced stimulation of gastric emptying, gastric acidity, and acid output. Since pr-MDI (30 mg/kg, i.p.) significantly inhibited the stimulation of gastric motility by both cold-restraint stress and TRH, but only cold-restraint stress-induced gastric erosions were effectively reduced by the drug, the present findings suggest a possible dissociation between the ulcerogenic mechanisms of cold-restraint stress and intracisternal administration of TRH.
Wong
W S
WS
Division of Pharmacology, College of Pharmacy, Ohio State University, Columbus 43210.
Rahwan
R G
RG
Stephens
R L
RL
D000818:Animals; D000897:Anti-Ulcer Agents / Q000627:therapeutic use*; D002121:Calcium Channel Blockers / Q000627:therapeutic use*; D003080:Cold Temperature; D005744:Gastric Acid / Q000378:metabolism; D005746:Gastric Emptying / Q000187:drug effects; D005750:Gastric Juice / Q000187:drug effects; D007192:Indenes / Q000627:therapeutic use*; D008297:Male; D011761:Pyrrolidonecarboxylic Acid / Q000031:analogs & derivatives; D051381:Rats; D011919:Rats, Inbred Strains; D012149:Restraint, Physical; D013276:Stomach Ulcer / Q000139:chemically induced / Q000188:drug therapy* / Q000209:etiology; D013315:Stress, Psychological; D013973:Thyrotropin-Releasing Hormone / Q000031:analogs & derivatives / Q000494:pharmacology
D000897:Anti-Ulcer Agents; D002121:Calcium Channel Blockers; D007192:Indenes; D013973:Thyrotropin-Releasing Hormone; C027979:L-pyroglutamyl-L-histidyl-3,3-dimethylprolinamide; C064266:propylmethylenedioxyindene; D011761:Pyrrolidonecarboxylic Acid