Secretagogues stimulate prostaglandin synthesis and inhibit mucosal damage induced by a necrotizing agent in rat gastric mucosa.
The effects of three kinds of secretagogues on the concentration and biosynthetic activity of prostaglandin (PG) E2 in rat gastric mucosa were examined. We also studied whether these secretagogues can protect gastric mucosa against 0.6 N HCl-induced mucosal damage. Histamine, carbamylcholine chloride (carbachol), or tetragastrin were given subcutaneously 30 or 60 min before the rats were killed. The PGE2 level in the fundic mucosa was measured. PGE2 synthesis in isolated gastric mucosa incubated with histamine, carbachol, or tetragastrin was also assayed. Gastric mucosal injury and protection was assessed according to Robert's method. The level of mucosal PGE2 was increased by histamine, carbachol, or tetragastrin in a dose-related way. The synthesis of PGE2 was increased by histamine, and this effect was inhibited by the addition of cimetidine. Carbachol slightly stimulated PGE2 synthesis, but tetragastrin had no such effect. Histamine (4-20 mg/kg) significantly prevented gastric damage induced by 0.6 N HCl judged macroscopically; this effect was overcome by cimetidine. Carbachol protected the rat gastric mucosa from damage induced by 0.6N HCl, and this effect was diminished by pirenzepine. Tetragastrin (4 micrograms/kg) significantly reduced gastric necrosis caused by 0.6 N HCl in a dose-related manner. We concluded that secretagogues such as histamine, carbachol, or tetragastrin through increasing endogenous PGE2 protect the gastric mucosa.
Kobayashi
K
K
Third Department of Internal Medicine, Osaka City University Medical School, Japan.
Nakamura
H
H
Arakawa
T
T
D000818:Animals; D002217:Carbachol / Q000494:pharmacology*; D002927:Cimetidine / Q000494:pharmacology; D015232:Dinoprostone / Q000032:analysis; D005753:Gastric Mucosa / Q000032:analysis / Q000187:drug effects* / Q000378:metabolism; D005755:Gastrins / Q000494:pharmacology*; D006632:Histamine / Q000494:pharmacology*; D008297:Male; D010295:Parietal Cells, Gastric / Q000187:drug effects / Q000378:metabolism; D011453:Prostaglandins / Q000096:biosynthesis*; D051381:Rats; D011919:Rats, Inbred Strains; D013758:Tetragastrin / Q000494:pharmacology*
D005755:Gastrins; D011453:Prostaglandins; D013758:Tetragastrin; D002927:Cimetidine; D006632:Histamine; D002217:Carbachol; D015232:Dinoprostone