Stimulation of prostaglandin E2 release from cultured rabbit gastric cells by sodium deoxycholate.
Although bile salts are irritants in the gastric mucosa, their effects on prostaglandin (PG) release have not been well studied. We investigated the effects of bile salts on PGE2 release and the possible mechanisms involved. Cultured rabbit gastric mucous epithelial cells were studied. PGE2 was measured by radioimmunoassay. Intracellular free Ca2+ concentration was measured with Ca2+ fluorescent dye indo-1 AM. Dihydroxy bile salts, such as chenodeoxycholate and deoxycholate (DC), dose-dependently increased PGE2 release, while non-dihydroxy bile salts did not. Since agents involved in the cellular signal transduction system have been reported to play important roles in PG release, the possible involvement of Ca2+, calmodulin, and protein kinase C (PKC) in DC-induced PGE2 release was studied. Deprivation of Ca2+ from the medium blocked DC-induced PGE2 release. Lanthanum (La3+), which displaced surface-bound Ca2+, suppressed DC-induced PGE2. However, BAPTA (a chelator of intracellular Ca2+) did not decrease it. Neither calmodulin inhibitors nor PKC inhibitors altered DC-induced PGE2 release. DC increased intracellular free Ca2+ concentrations. This effect was blocked by deprivation of Ca2+ from the medium. Quinacrine (a phospholipase A2 inhibitor) blocked DC-induced PGE2 release. These results suggest that in cultured rabbit gastric cells, deoxycholate stimulates PGE2 release mainly through the influx of extracellular Ca2+.
Hata
Y
Y
2nd Department of Internal Medicine, Faculty of Medicine, University of Tokyo, Japan.
Ota
S
S
Terano
A
A
Kohmoto
O
O
Yoshiura
K
K
Okano
K
K
Ivey
K J
KJ
Sugimoto
T
T
D000818:Animals; D002118:Calcium / Q000378:metabolism; D002478:Cells, Cultured; D002857:Chromium / Q000378:metabolism; D002860:Chromium Radioisotopes; D003840:Deoxycholic Acid / Q000494:pharmacology*; D015232:Dinoprostone / Q000378:metabolism*; D004305:Dose-Response Relationship, Drug; D005748:Gastric Fundus / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D005753:Gastric Mucosa / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D008954:Models, Biological; D011817:Rabbits; D011863:Radioimmunoassay; D015398:Signal Transduction; D018675:Toxicity Tests
D002860:Chromium Radioisotopes; D003840:Deoxycholic Acid; D002857:Chromium; D015232:Dinoprostone; D002118:Calcium