Stimulation of prostaglandin E2 release from cultured rabbit gastric cells by sodium deoxycholate

Abstract 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 PGE 2 release and the possible mechanisms involved. Cultured rabbit gastric mucous epithelial cells were studied. PGE 2 was measured by radioimmunoassay. Intracellular free Ca 2+ concentration was measured with Ca 2+ fluorescent dye indo-1 AM. Dihydroxy bile salts, such as chenodeoxycholate and deoxycholate (DC), dose-dependently increased PGE 2 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 Ca 2+ , calmodulin, and protein kinase C (PKC) in DC-induced PGE 2 release was studied. Deprivation of Ca 2+ from the medium blocked DC-induced PGE 2 release. Lanthanum (La 3+ ), which displaced surface-bound Ca 2+ , suppressed DC-induced PGE 2 . However, BAPTA (a chelator of intracellular Ca 2+ ) did not decrease it. Neither calmodulin inhibitors nor PKC inhibitors altered DC-induced PGE 2 release. DC increased intracellular free Ca 2+ concentrations. This effect was blocked by deprivation of Ca 2+ from the medium. Quinacrine (a phospholipase A 2 inhibitor) blocked DC-induced PGE 2 release. These results suggest that in cultured rabbit gastric cells, deoxycholate stimulates PGE 2 release mainly through the influx of extracellular Ca 2+ .