STIMULATION OF PROSTAGLANDIN E(2) 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 investig ated the effects of bile salts on PGE(2) release and the possible mech anisms involved. Cultured rabbit gastric mucous epithelial cells were studied. PGE(2) was measured by radioimmunoassay. Intracellular free C a2+ concentration was measured with Ca2+ fluorescent dye indo-1 AM. Di hydroxy bile salts, such as chenodeoxycholate and deoxycholate (DC), d ose-dependently increased PGE(2) release, while non-dihydroxy bile sal ts did not. Since agents involved in the cellular signal transduction system have been reported to play important roles in PG release, the p ossible involvement of Ca2+, calmodulin, and protein kinase C (PKC) in DC-induced PGE(2) release was studied. Deprivation of Ca2+ from the m edium blocked DC-induced PGE(2) release. Lanthanum (La3+), which displ aced surface-bound Ca2+, suppressed DC-induced PGE(2). However, BAPTA (a chelator of intracellular Ca2+) did not decrease it. Neither calmod ulin inhibitors nor PKC inhibitors altered DC-induced PGE(2) release. DC increased intracellular free Ca2+ concentrations. This effect was b locked by deprivation of Ca2+ from the medium. Quinacrine (a phospholi pase 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 Ca2+.