CERULEIN-STIMULATED ARACHIDONIC-ACID RELEASE IN RAT PANCREATIC ACINI - A DIACYLGLYCEROL LIPASE AFFAIR

This study was performed to evaluate the effect of caerulein, a cholec ystokinin analogue, on arachidonic acid (AA) release in rat pancreatic acini and to determine the cellular mechanism involved. Caerulein did not stimulate phospholipase A(2) (PLA(2)); however, diacylglycerol (D AG) lipase activity was increased. Validity of PLA(2) or DAG lipase in hibitors was confirmed by their ability to selectively inhibit PLA(2) or DAG lipase activities. Caerulein increased AA release from acini pr elabeled with [H-3]AA both dose and time dependently. Inhibitors were used to evaluate the involvement of different signaling pathways. Mepa crine and aristolochic acid, two PLA(2) inhibitors, did not inhibit ca erulein-induced AA release, whereas the DAG lipase inhibitor RHC-80267 did. The phospholipase C (PLC) inhibitor U-73122 totally inhibited ca erulein-induced AA release, whereas the phospholipase D (PLD) inhibito r wortmannin had no effect. Our data indicate that caerulein-induced A A release results from the combined action of PLC and DAG lipase witho ut PLA(2) or PLD activation.