Endogenous arachidonic acid release and pancreatic amylase secretion.

Recent studies have suggested the involvement of phospholipase A2 (PLA2) in pancreatic amylase secretion. The present study was designed to investigate the secretory role of arachidonic acid (AA) in carbachol (Cch)-stimulated rat pancreatic acini and its origin. From enzymatic assays, PLA2 and diacylglycerol (DAG) lipase were activated by Cch and respectively inhibited by the PLA2 inhibitors, mepacrine and aristolochic acid, and by the DAG lipase inhibitor, RHC 80267. Melittin-activated PLA2 activity was also inhibited by the PLA2 inhibitors. Cch-stimulated endogenous AA release from pancreatic acini was partially inhibited by 150 microM RHC 80267 and by 150 microM mepacrine or 200 microM aristolochic acid and totally inhibited by a combination of the two enzyme inhibitors. Exogenous AA caused amylase release in a concentration-dependent manner. Eicosatetraynoic acid (a cyclooxygenase and lipoxygenase inhibitor), significantly increased basal and Cch-induced AA release and amylase secretion. RHC 80267 and the PLA2 inhibitors separately and partially suppressed Cch-stimulated amylase secretion, with an additive effect observed when the DAG lipase and the PLA2 inhibitors were combined. A combination of RHC 80267, mepacrine, or aristolochic acid and the phospholipase C (PLC) inhibitor U73122 completely inhibited Cch-stimulated amylase secretion. Finally, the PLA2 activator melittin-stimulated amylase secretion was blocked by the two PLA2 inhibitors. We conclude that exogenous and endogenous AA can induce amylase secretion. Therefore, AA released from either PLC-DAG lipase or PLA2 pathways can be considered an additional and important intracellular mediator of amylase secretion.