Adaptive cytoprotection in cultured rat gastric mucus-producing cells. Role of mucus and prostaglandin synthesis.
In cultured gastric mucosal cells, we investigated whether: (1) adaptive cytoprotection was associated with stimulation of endogenous prostaglandin synthesis; (2) prostaglandins given exogenously were cytoprotective against ethanol-induced gastric mucosal cell damage; and (3) a relationship existed between cytoprotection and mucus release. Cytolysis was quantified by measuring 51Cr release from prelabeled cells. Mucus release was determined by measurement of [3H]glucosamine release. Concentrations of ethanol > 12% caused cell damage and increased 51Cr release dose dependently. Pretreatment with low concentrations of ethanol (0.5-1.5%) decreased ethanol-induced 51Cr release, but also decreased prostaglandin E2 synthesis. Prostaglandin E2 and 16,16-dimethyl prostaglandin E2 given exogenously were cytoprotective against ethanol-induced gastric mucosal cell damage. Treatment with low concentrations of ethanol (1.5%) increased mucus release from cultured gastric mucosal cells. However, prostaglandin E2 and 16,16-dimethyl prostaglandin E2 did not affect mucus release. We conclude that in cultured gastric mucus-producing cells: (1) adaptive cytoprotection occurs without stimulation of endogenous prostaglandin synthesis but with increase in mucus release; and (2) exogenous prostaglandins are cytoprotective against ethanol-induced gastric mucosal cell damage without stimulating mucus release in vitro. We postulate that adaptive cytoprotection in cultured gastric mucus-producing cells is not mediated by prostaglandin, but by mucus released in response to a mild irritant.
Mutoh
H
H
Second Department of Internal Medicine, Faculty of Medicine, University of Tokyo, Japan.
Ota
S
S
Hiraishi
H
H
Ivey
K J
KJ
Terano
A
A
Sugimoto
T
T
D015064:16,16-Dimethylprostaglandin E2 / Q000494:pharmacology; D000818:Animals; D002478:Cells, Cultured; D015232:Dinoprostone / Q000096:biosynthesis* / Q000494:pharmacology; D000431:Ethanol / Q000633:toxicity; D005260:Female; D005753:Gastric Mucosa / Q000187:drug effects / Q000378:metabolism* / Q000473:pathology; D007509:Irritants; D008297:Male; D009093:Mucus / Q000378:metabolism*; D051381:Rats; D017207:Rats, Sprague-Dawley
D007509:Irritants; D000431:Ethanol; D015232:Dinoprostone; D015064:16,16-Dimethylprostaglandin E2