Pathways of Arachidonic Acid Release in Platelets

Thromboxane syn esis in platelets is triggered by the release of AA from platelet membrane phospholipids (14). This initial release appears to occur through activation of two major pathways a) the first pathway involves a sequoitial hydrolysis of 1, 2-diacylglycerol (DAG) fcxmed during platelet receptm -coupled activatirm of phospholipase C/D (PLC/PLD), by DAG- and monoacylglycerol (MAG) lipases, re )ectivefy (21,22). We have shown that hydrolysis of DAG by this pathwty results equimolar amounts of saturated fat acids (stearic palmitic acids) fixxn the sn-1 position and unsaturated fatty acids [oleic acid (18 1, i -9), linoleic acid (18 2, co-6) and 

AA (b -6)] fixHn the sn-2 positicm of platelet phospholipids (22). The majm source of DAG appears to be predcxninantly c ved Wn pho hoinositides, whidi are rich in 1-stearoyl 2-arachi kMK yl species (18, 22). Althmigh 1-stearoyl 2-arachid(H]oyl DAG species m also come fimn a PLD-mediated hydrolysis of phospholipids, it is less clear as to the extmt of amtributirm from this pathway fix die release of AA. FurthomcHe, the DAG lipase pathway appears to be an unlikely route fw the release 

Alternatively, the release of platelet phospholipid AA is mediated by the activation of phospholipase Aj (PIA) coupled to PLC, intracellular Ca rise and protein kinase C (PKC) and tyrosine kinase-mediated protein phosphorylations (23,24) and/or by the activation of PLA that is not coupled to these events in platelets (25-29). Furthermore, the hydrolysis of phosphatidic acid (PA) by a PA-specific PLAj may also contribute to eicosanoid synthesis (30,31). It is evident that the differential sensitivity of platelets to multiple agonists and their signals, have contributed to the complexity in understanding the regulation of PLAj. 

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