Effects of TY-10957, a stable PGI2 derivative, on gastroduodenal lesions and secretory responses in the rat.
The effects of TY-10957, a stable PGI2 derivative, on gastroduodenal lesions and secretory responses were examined in rats and compared with those of ornoprostil, a PGE1 derivative. Orally administered TY-10957 dose dependently prevented gastric lesions induced by ethanol/HC1 (60% ethanol in 150 mM HCl) and duodenal ulcers induced by mepirizole (200 mg/kg); a significant effect was obtained at 3 micrograms/kg or greater in the former and at 300 micrograms/kg in the latter. Intraduodenally administered TY-10957 had minimal effects on gastric acid secretion, and at the highest dose (300 micrograms/kg) both the basal acid output and that stimulated by histamine (20 mg/kg) were significantly reduced by about 40%. TY-10957 (30-300 micrograms/kg s.c.) produced a marked increase of alkaline secretion in both stomach and duodenum of anesthetized rats, and these effects were significant at 30 micrograms/kg in the stomach and at 100 micrograms/kg in the duodenum. On the other hand, ornoprostil produced a potent and significant inhibition against ethanol/HCl-induced lesions (greater than 1 microgram/kg), but had no effect on mepirizole-induced duodenal ulcers. This PGE1 derivative had no influence on both basal and stimulated acid secretion and did not significantly affect alkaline secretion even at 100 micrograms/kg. These results suggest that TY-10957 has a protective action on both gastric and duodenal mucosa. The mechanism of duodenal antiulcer effect may involve both inhibition of acid and stimulation of alkaline secretion, while the gastroprotective action of this agent may be attributed to other factors.
Okabe
S
S
Department of Applied Pharmacology, Pharmaceutical University, Kyoto, Japan.
Takeuchi
K
K
Niida
H
H
Takinami
Y
Y
D000527:Alprostadil / Q000031:analogs & derivatives / Q000627:therapeutic use; D000818:Animals; D000897:Anti-Ulcer Agents / Q000627:therapeutic use*; D004840:Epirizole / Q000633:toxicity; D011464:Epoprostenol / Q000627:therapeutic use* / Q000031:analogs & derivatives; D000431:Ethanol / Q000633:toxicity; D005744:Gastric Acid / Q000378:metabolism; D008297:Male; D010437:Peptic Ulcer / Q000139:chemically induced / Q000188:drug therapy*; D011459:Prostaglandins E, Synthetic / Q000627:therapeutic use; D011465:Prostaglandins, Synthetic / Q000627:therapeutic use*; D051381:Rats; D011919:Rats, Inbred Strains
D000897:Anti-Ulcer Agents; D011459:Prostaglandins E, Synthetic; D011465:Prostaglandins, Synthetic; C064521:TY 10957; D004840:Epirizole; D000431:Ethanol; D011464:Epoprostenol; D000527:Alprostadil; C045125:ornoprostil