The production of phosphatidic acid (PA) from phosphoAbstract When rat polymorphonuclear neutrophils (PMN) were treated with N-formyI-Met-Leu-Phe (fMLP), the release lipase D (PLD)-catalyzed hydrolysis of phosphatidylcholine is of araehidonie acid in preference to other fatty acids was a rapid and widespread response of cells stimulated with diobserved. Levels of arachidonic acid reached a plateau within verse agonists, and is implicated in a broad spectrum of 5 rain, and were accompanied by an ,-~ 4-fold increase in in vitro physiological and pathological processes, such as exocytosis, phospholipase (PL) A2 and PLD activities in PMN lysates, mitogenesis, oncogenesis and inflammation (reviewed in [4]).
Treatment of PMN with ethanol (an inhibitor of PLD-mediatedThere are also several lines of evidence to suggest that arachiphosphatidic acid formation), propranolol (a phosphatiflic acid donic acid release correlates with PLD activation. Arachidonphosphatase inhibitor), or 4-bromophenaeylbromide (a PLA2 ic acid release by activated cells is reported to be accompanied inhibitor), each suppressed fMLP-stimulated araehidonate reby the increase in PLD activity and inhibition of PLD by lease. Treatment with RHC-80267 (a diaeylglyeerol lipase ethanol is associated with the decrease in arachidonic acid inhibitor), however, had no such effect. The eytosolie PLA2 release [5][6][7][8][9][10]. To account for these observations, some inves-(ePLA2) inhibitor, araehidonoyl trifluoromethyl ketone, suppressed PLA2 activity in PMN homogenates and araehidonate tigators have proposed that the PA generated by the PLD release by fMLP-treated PMN. These results suggest that reaction is converted to diacylglycerol (DG) by PA phosphatfMLP-elicited arachidonate release is mediated by cPLA2 but ase, and that arachidonic acid is released from DG by DG not diacylglycerol lipase, and that the activation of cPLA2 is lipase [6,7]. In contrast to this 'indirect' model for arachidonic downstream of the PLD-dependent signaling pathway, acid release via DG, other investigators have proposed that arachidonic acid is 'directly' released from phospholipids by
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