Effect of calcium channel blocker diltiazem on cytoprotection and prostaglandin and sulfhydryl production by rat gastric epithelial cells.
The calcium channel blockers verapamil and diltiazem protect gastric mucosa against exogenous injury in vivo. Whether this protection is mediated by systemic factors, such as blood flow, is due to inhibition of gastric acid secretion, or is associated with stimulation of endogenous protective agents such as prostaglandins or sulfhydryls, is unknown. We have evaluated whether diltiazem protects rat gastric epithelial cells in tissue culture (a model which excludes the influence of systemic factors) against damage induced by sodium taurocholate, indomethacin, or ethanol. Further we have assessed the effect of diltiazem on prostaglandin and sulfhydryl production. 51Chromium release assay and phase contrast microscopy have been used to assess cell damage. Sodium taurocholate, indomethacin, and ethanol-damaged cultured cells in a dose-dependent manner. Pretreatment with diltiazem did not prevent the drug-induced damage. Diltiazem did not increase PGE2 and 6-keto PGF1a production by cultured cells nor did it affect the cellular level of endogenous sulfhydryls. In conclusion, the calcium channel blocker diltiazem is not directly protective to rat gastric mucosal cells in vitro. Diltiazem does not stimulate prostaglandin production by gastric cells nor does it increase the cellular level of protective sulfhydryls.
Romano
M
M
Department of Medicine, Long Beach Veterans Administration Medical Center, California.
Razandi
M
M
Ivey
K J
KJ
D015121:6-Ketoprostaglandin F1 alpha / Q000096:biosynthesis; D000818:Animals; D002478:Cells, Cultured; D004110:Diltiazem / Q000494:pharmacology*; D015232:Dinoprostone / Q000096:biosynthesis; D004848:Epithelium / Q000187:drug effects / Q000378:metabolism; D000431:Ethanol / Q000494:pharmacology; D005753:Gastric Mucosa / Q000187:drug effects* / Q000378:metabolism; D007213:Indomethacin / Q000494:pharmacology; D011453:Prostaglandins / Q000096:biosynthesis*; D051381:Rats; D011919:Rats, Inbred Strains; D013438:Sulfhydryl Compounds / Q000096:biosynthesis*; D013656:Taurocholic Acid / Q000494:pharmacology; D014700:Verapamil / Q000494:pharmacology
D011453:Prostaglandins; D013438:Sulfhydryl Compounds; D000431:Ethanol; D015121:6-Ketoprostaglandin F1 alpha; D013656:Taurocholic Acid; D014700:Verapamil; D004110:Diltiazem; D015232:Dinoprostone; D007213:Indomethacin