ENDOGENOUS ARACHIDONIC-ACID RELEASE AND PANCREATIC AMYLASE SECRETION

Recent studies have suggested the involvement of phospholipase A(2) (P LA(2)) in pancreatic amylase secretion. The present study was designed to investigate the secretory role of arachidonic acid (AA) in carbach ol (Cch)-stimulated rat pancreatic acini and its origin. From enzymati c assays, PLA(2) and diacylglycerol (DAG) lipase were activated by Cch and respectively inhibited by the PLA(2) inhibitors, mepacrine and ar istolochic acid, and by the DAG lipase inhibitor, RHC 80267. Melittin- activated PLA(2) activity was also inhibited by the PLA(2) inhibitors. Cch-stimulated endogenous AA release from pancreatic acini was partia lly inhibited by 150 mu M RHC 80267 and by 150 mu M mepacrine or 200 m u M aristolochic acid and totally inhibited by a combination of the tw o enzyme inhibitors. Exogenous AA caused amylase release in a concentr ation-dependent manner. Eicosatetraynoic acid (a cyclooxygenase and li poxygenase inhibitor), significantly increased basal and Cch-induced A A release and amylase secretion. RHC 80267 and the PLA(2) inhibitors s eparately and partially suppressed Cch-stimulated amylase secretion, w ith an additive effect observed when the DAG lipase and the PLA(2) inh ibitors were combined. A combination of RHC 80267, mepacrine, or arist olochic acid and the phospholipase C (PLC) inhibitor U73122 completely inhibited Cch-stimulated amylase secretion. Finally, the PLA(2) activ ator melittin-stimulated amylase secretion was blocked by the two PLA( 2) inhibitors. We conclude that exogenous and endogenous AA can induce amylase secretion. Therefore, AA released from either PLC-DAG lipase or PLA(2) pathways can be considered an additional and important intra cellular mediator of amylase secretion.