Effect of 16,16 dimethyl prostaglandin E2 on aspirin induced damage to rat gastric epithelial cells in tissue culture.
Prostaglandins (PGs) protect gastric mucosa against damage produced by acetylsalicylic acid (ASA). Whether this effect of prostaglandins is truly cytoprotective and whether cAMP plays an important role in this effect is uncertain. We studied the effect of: (1) 16,16 dimethyl prostaglandin E2 (dmPGE2), isobutylmethyl xanthine (IMX), and dibutyryl cAMP (DBcAMP) on ASA-induced damage to monolayer cultures of rat gastric mucosa composed primarily of mucus cells; (2) dmPGE2 on ASA absorption into the cultured cells. Cell damage was quantitated by 51Cr-release and trypan blue staining. Ten millimoles ASA significantly increased 51Cr-release (indicating cell damage) at pH 5.0, but not at pH 7.4. DmPGE2 significantly reduced ASA-induced increase of 51Cr-release. Isobutylmethyl xanthine did not change the rate of 51Cr-release caused by ASA plus dmPGE2. Dibutyryl cAMP did not significantly alter 51Cr-release caused by ASA. A dose response study of ASA damage showed close correlation between 51Cr-release and trypan blue staining (r = 0.93). Dimethyl prostaglandin E2 did not affect 14C-ASA incorporation by the cells at either pH 7.4 or pH 5.0. We conclude that: (1) dmPGE2 exerts a cytoprotective effect on cultured rat gastric cells; (2) cAMP does not play an important role in such cytoprotection; (3) this protection is not because of interference with ASA absorption by prostaglandin.
D015056:1-Methyl-3-isobutylxanthine / Q000494:pharmacology; D015064:16,16-Dimethylprostaglandin E2 / Q000494:pharmacology*; D000042:Absorption; D000818:Animals; D001241:Aspirin / Q000378:metabolism / Q000494:pharmacology*; D003994:Bucladesine / Q000494:pharmacology; D002470:Cell Survival / Q000187:drug effects; D002478:Cells, Cultured; D002860:Chromium Radioisotopes / Q000378:metabolism; D004847:Epithelial Cells; D004848:Epithelium / Q000187:drug effects; D005753:Gastric Mucosa / Q000187:drug effects* / Q000378:metabolism; D011459:Prostaglandins E, Synthetic / Q000494:pharmacology*; D051381:Rats; D011919:Rats, Inbred Strains
D002860:Chromium Radioisotopes; D011459:Prostaglandins E, Synthetic; D003994:Bucladesine; D015064:16,16-Dimethylprostaglandin E2; D001241:Aspirin; D015056:1-Methyl-3-isobutylxanthine