When rat polymorphonuclear neutrophils (PMN) were treated with N-formyl-Met-Leu-Phe (fMLP), the release of arachidonic acid in preference to other fatty acids was observed. Levels of arachidonic acid reached a plateau within 5 min, and mere accompanied by an ~ 4-fold increase in in vitro phospholipase (PL) A2 and PLD activities in PMN lysates. Treatment of PMN with ethanol (an inhibitor of PLD-mediated phosphatidic acid formation), propranolol (a phosphatidic acid phosphatase inhibitor), or 4-bromophenacylbromide (a PLA2 inhibitor), each suppressed fMLP-stimulated arachidonate release. Treatment with RHC-80267 (a diacylglycerol lipase inhibitor), however, had no such effect. The cytosolic PLA2 (cPLA2) inhibitor, arachidonoyl trifluoromethyl ketone, suppressed PLA2 activity in PMN homogenates and arachidonate release by fMLP-treated PMN. These results suggest that fMLP-elicited arachidonate release is mediated by cPLA2 but not diacylglycerol lipase, and that the activation of cPLA2 is downstream of the PLD-dependent signaling pathway.
Fujita, K. I., Murakami, M., Yamashita, F., Amemiya, K., & Kudo, I. (1996). Phospholipase D is involved in cytosolic phospholipase A2-dependent selective release of arachidonic acid by fMLP-stimulated rat neutrophils. FEBS Letters, 395(2–3), 293–298. https://doi.org/10.1016/0014-5793(96)01056-3