Metabolism of arachidonic acid by pancreatic acini: relation to amylase secretion.

Isolated guinea pig pancreatic acini were incubated with exogenous [14C]arachidonic acid (10 microM) at 37 degrees C for 3 min. The lipids were extracted and separated by thin-layer chromatography. Radiolabeled metabolites were identified by comigration with standards: 0.024% of the recovered radioactivity comigrated with prostaglandin E2 (PGE2), 0.016% comigrated with PGF2 alpha, 4.9% was incorporated into triglycerides, 1.8% was incorporated into phospholipids, and 93.2% remained as arachidonic acid. The synthesis of PGE2 and PGF2 alpha was inhibited by indomethacin (ID50, 30 nM). Simultaneous addition of carbachol or caerulein with the [14C]arachidonic acid did not alter the metabolism of the arachidonate. Further studies were done on the role of arachidonate metabolites in the secretion of amylase. Exogenously added PGE2 and PGF2 alpha (0.3-100 nM) did not induce amylase secretion from isolated acini. Incubation of isolated acini with indomethacin (0.1-28 microM) did not inhibit the release of amylase induced by carbachol or caerulein. From these data, we conclude that isolated guinea pig pancreatic acini are capable of converting a small percentage of exogenous arachidonate to PGE2 and PGF2 alpha. However, there is no evidence for a role of these compounds in stimulus-secretion coupling.