STORE-OPERATED CALCIUM INFLUX IN HUMAN GASTRIC CELLS - ROLE OF ENDOGENOUS PROSTAGLANDINS

Background Store-operated calcium influx (SOCI) appears to be a key co mponent in regulating processes such as gene expression and cellular m etabolism in nonexcitable cells. Our objective was to determine what e ffect, if any, prostaglandin inhibition had on SOCI in human gastric c ells. Methods. SOCI was induced in human gastric cells (AGS) with thap sigargin, a microsomal Ca++ adenosine triphosphatase inhibitor Quantit ation of SOCI was achieved by two different methods: sustained intrace llular calcium elevation and manganese (Mn++) uptake. Endogenous prost aglandin E-2 (PGE(2)) synthesis was measured by enzyme immunoassay. Th ree different nonsteroidal anti-inflammatory drugs (NSAIDs; indomethac in, ibuprofen, and aspirin) were used to minimize the nonspecific acti ons of any individual agent. Results. SOCI in AGS cells was inhibited by the store-operated Ca++ channel blocker lanthanum (La+++) but not t he voltage-operated Ca++ channel antagonists verapamil or nifedipine. Each of the three NSAIDs equally inhibited SOCI. The inhibition of SOC I induced, by indomethacin was partially reversed by the addition of e xogenous PGE2. Finally, AGS cells exposed to thapsigargin demonstrated significantly increased endogenous PGE2 release. Conclusions, These d ata suggest that NSAIDs inhibit (or endogenous prostaglandins modulate ) SOCI in human gastric cells, at least in part. Because SOCI appears to be a critical mechanism involved in cell proliferation, this may pr ovide one explanation of how NSAIDs inhibit (and endogenous prostaglan dins enhance) gastric epithelial renewal and repair.