Caerulein-stimulated arachidonic acid release in rat pancreatic acini: a diacylglycerol lipase affair.
This study was performed to evaluate the effect of caerulein, a cholecystokinin analogue, on arachidonic acid (AA) release in rat pancreatic acini and to determine the cellular mechanism involved. Caerulein did not stimulate phospholipase A2 (PLA2); however, diacylglycerol (DAG) lipase activity was increased. Validity of PLA2 or DAG lipase inhibitors was confirmed by their ability to selectively inhibit PLA2 or DAG lipase activities. Caerulein increased AA release from acini prelabeled with [3H]AA both dose and time dependently. Inhibitors were used to evaluate the involvement of different signaling pathways. Mepacrine and aristolochic acid, two PLA2 inhibitors, did not inhibit caerulein-induced AA release, whereas the DAG lipase inhibitor RHC-80267 did. The phospholipase C (PLC) inhibitor U-73122 totally inhibited caerulein-induced AA release, whereas the phospholipase D (PLD) inhibitor wortmannin had no effect. Our data indicate that caerulein-induced AA release results from the combined action of PLC and DAG lipase without PLA2 or PLD activation.
Hou
W
W
Département de Médecine, Faculté de Médecine, Université de Sherbrooke, Quebec, Canada.
Arita
Y
Y
Morisset
J
J
D000730:Androstadienes / Q000494:pharmacology; D000818:Animals; D016718:Arachidonic Acid / Q000378:metabolism*; D034341:Aristolochic Acids; D002217:Carbachol / Q000494:pharmacology; D002478:Cells, Cultured; D002108:Ceruletide / Q000494:pharmacology*; D003512:Cyclohexanones / Q000494:pharmacology; D016861:Cyclooxygenase Inhibitors / Q000494:pharmacology; D004791:Enzyme Inhibitors / Q000494:pharmacology; D004963:Estrenes / Q000494:pharmacology; D007700:Kinetics; D008071:Lipoprotein Lipase / Q000037:antagonists & inhibitors / Q000378:metabolism*; D016859:Lipoxygenase Inhibitors / Q000494:pharmacology; D008297:Male; D010179:Pancreas / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D010616:Phenanthrenes / Q000494:pharmacology; D010739:Phospholipase D / Q000037:antagonists & inhibitors; D010741:Phospholipases A / Q000037:antagonists & inhibitors / Q000378:metabolism; D054467:Phospholipases A2; D011760:Pyrrolidinones / Q000494:pharmacology; D011796:Quinacrine / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D000077191:Wortmannin
D000730:Androstadienes; D034341:Aristolochic Acids; D003512:Cyclohexanones; D016861:Cyclooxygenase Inhibitors; D004791:Enzyme Inhibitors; D004963:Estrenes; D016859:Lipoxygenase Inhibitors; D010616:Phenanthrenes; D011760:Pyrrolidinones; C060229:1-(6-((3-methoxyestra-1,3,5(10)-trien-17-yl)amino)hexyl)-1H-pyrrole-2,5-dione; D016718:Arachidonic Acid; C036535:1,6-bis(cyclohexyloximinocarbonyl)hexane; D002108:Ceruletide; D002217:Carbachol; C000228:aristolochic acid I; D010741:Phospholipases A; D008071:Lipoprotein Lipase; D054467:Phospholipases A2; D010739:Phospholipase D; D011796:Quinacrine; D000077191:Wortmannin