PACAP-38 CAUSES PHOSPHOLIPASE C-DEPENDENT CALCIUM SIGNALING IN RAT ACINAR CELL-LINE

Background. Pituitary adenylate cyclase activating peptide (PACAP-38) a neuropeptide of she vasoactive intestinal peptide/secretin family, l ocalizes to intrapancreatic neurons and stimulates exocrine secretion from the pancreas. PACAP-38 stimulates calcium signaling in the rat pa ncreatic cell line AR42J. The purpose of this study was to elucidate t he mechanisms of PACAP-evoked calcium signaling in these cells. Method s. Continuous measurements of intracellular calcium were taken by fluo rescent digital microscopy with the dye fura-2. Mechanisms of PACAP-38 -evoked calcium signals were determined by a panel of inhibitors. Inos itol phosphates Production in response to PACAP-38 was measured. The a bility of PACAP-38 to stimulate amylase release was used to determine a relevant dose range for these studies. Results. We have shown that ( 1) AR42J cells respond to PACAP-38 with biphasic increases in [Ca2+](i ) in a dose-dependent fashion; (2) PACAP-38 acts through phospholipase C to release inositol triphosphate (IP3)-sensitive Ca2+ stores with ( 3) a subsequent influx of extracellular Ca2+. Conclusions. PACAP-38 ac tivates calcium signaling through phospholipase C at concentrations th at stimulate amylase release in AR42J cells.