Effect of cimetidine on indomethacin-induced damage in cultured rat gastric mucosal cells; comparison with prostaglandin.
Whether cimetidine protects gastric mucosal cells independently of its antisecretory effect has been controversial. Some investigators postulate that, on the contrary, cimetidine decreases the integrity of gastric mucosa. Furthermore, whether cimetidine influences gastric prostaglandin (PG) synthesis is debated. Therefore, we investigated and compared with 16,16-dimethyl-PGE2 (dmPGE2) whether cimetidine protects cultured rat gastric mucosal cells from indomethacin, and tested whether cimetidine affects gastric PG production by these cells. Cell damage was assessed by chromium 51-release assay. Concentrations of indomethacin greater than 1 mmol/L caused cell damage and increased 51Cr release in a dose-dependent and time-dependent fashion. dmPGE2 significantly reduced indomethacin-induced increase of 51Cr release, whereas cimetidine at both nonantisecretory and antisecretory doses did not alter 51Cr release caused by indomethacin. The cultured cells released PGE2 and PGI2 in amounts of 215 +/-18 and 56 +/- 3 (mean +/- SEM) pg/10(5) cells in 1 hour, respectively. Nondamaging concentrations of indomethacin caused a dose-dependent inhibition of PG release from cultured cells with 50% inhibitory concentration at a dose of 10(-6) to 10(-7) mol/L. Cimetidine did not alter gastric PG production. In summary, exogenous PG protected gastric mucosal cells from indomethacin in vitro, but cimetidine did not. In conclusion, cimetidine, which fails to affect gastric PG production, does not directly influence the integrity of gastric mucosal cells.
Hiraishi
H
H
Terano
A
A
Ota
S
S
Ivey
K J
KJ
Sugimoto
T
T
D000818:Animals; D002857:Chromium / Q000378:metabolism; D002927:Cimetidine / Q000494:pharmacology*; D015232:Dinoprostone / Q000031:analogs & derivatives; D004305:Dose-Response Relationship, Drug; D005260:Female; D005753:Gastric Mucosa / Q000166:cytology / Q000187:drug effects*; D007213:Indomethacin / Q000494:pharmacology*; D008297:Male; D011453:Prostaglandins / Q000494:pharmacology*; D011458:Prostaglandins E / Q000494:pharmacology; D011459:Prostaglandins E, Synthetic / Q000494:pharmacology; D051381:Rats; D011919:Rats, Inbred Strains
D011453:Prostaglandins; D011458:Prostaglandins E; D011459:Prostaglandins E, Synthetic; D002857:Chromium; C032514:17,17-dimethylprostaglandin E2; D002927:Cimetidine; D015232:Dinoprostone; D007213:Indomethacin