Gastric protective effects of gastric secretagogues on 0.6N HCl-induced gastric lesions in rats.
The effects of gastric secretagogues on 0.6N HCl-induced gastric lesions and gastric mucosal prostaglandin E2 (PGE2) contents were investigated in rats. Secretagogues such as histamine (Hist) and amogastrin (Gast) significantly inhibited the formation of gastric lesions induced by 0.6N HCl. The time course of the gastric protective effect of these secretagogues paralleled the increase of gastric acid secretion. This increase was due to the increase in acidity, not to the volume of the gastric juice. The gastric protective effects of Hist and Gast were inhibited by pretreatment with cimetidine, timoprazole and indomethacin. Hist and Gast caused an increase of PGE2 contents in gastric mucosa. These increases were inhibited by the administration of cimetidine and timoprazole. Carbachol (CCh), however, did not have any gastric protective effect; nor did it have any effect on PGE2 contents. CCh caused an increase of acid secretion due to the increase of the volume of gastric juice, but not to an increase in acidity. These results suggest that the gastric protective effect of Hist and Gast, induced by the increase of acidity in gastric juice, is due to the endogenous PGE2 synthesized by the stimulation of acid in the gastric mucosa.
Isobe
Y
Y
Department of Pharmacology, Taisho Pharmaceutical Co., Ltd., Saitama, Japan.
Hirose-Kijima
H
H
Muramatsu
M
M
Aihara
H
H
D053799:2-Pyridinylmethylsulfinylbenzimidazoles; D000818:Animals; D000897:Anti-Ulcer Agents; D001562:Benzimidazoles / Q000494:pharmacology; D002927:Cimetidine / Q000494:pharmacology; D015232:Dinoprostone / Q000378:metabolism; D005753:Gastric Mucosa / Q000378:metabolism; D005755:Gastrins; D006632:Histamine; D006851:Hydrochloric Acid / Q000633:toxicity*; D008297:Male; D009853:Omeprazole / Q000031:analogs & derivatives; D011708:Pylorus / Q000502:physiology; D051381:Rats; D011919:Rats, Inbred Strains; D013270:Stomach / Q000187:drug effects; D013276:Stomach Ulcer / Q000139:chemically induced / Q000503:physiopathology / Q000517:prevention & control*
D053799:2-Pyridinylmethylsulfinylbenzimidazoles; D000897:Anti-Ulcer Agents; D001562:Benzimidazoles; D005755:Gastrins; D002927:Cimetidine; D006632:Histamine; C038402:timoprazole; D015232:Dinoprostone; D009853:Omeprazole; D006851:Hydrochloric Acid