INFLUX OF EXTRACELLULAR CALCIUM AND AGONIST-COUPLING APPEAR ESSENTIALFOR THE ACTIVATION OF THROMBOXANE A(2)-DEPENDENT PHOSPHOLIPASE A(2) IN HUMAN PLATELETS

The present study demonstrates the existence of a unique mechanism for arachidonic acid (AA)-specific phospholipase A(2) (PLA(2)) activation , which requires both sustained elevation of cytosolic Ca2+ coupled to the influx of extracellular Ca2+ and agonist interaction in platelets , The activation of PLA(2) in platelets exposed to thapsigargin was ab olished by the inhibition of cyclooxygenase (COX), thus suggesting,a r equirement of endogenously produced COX metabolite(s) for the activati on of this enzyme, A thromboxane A(2) (TXA(2)) analog, U46619, restore d the activation of this AA-specific PLA(2) activation supporting the requirements of COX metabolite(s) especially TXA(2). Our subsequent st udies demonstrated that both the effects of TXA(2), and U46619 could b e mimicked by collagen, Neither the transient cytosolic Ca2+ rise nor the agonists such as U46619 or collagen alone were sufficient to prime the activation of this PLA(2) in the absence of thapsigargin. Since c ollagen behaves very similarly to TXA(2), we suggest that this PLA(2), is not only responsive to TXA(2), but also to other agonists such as collagen, as shown in this study, We suggest that the activation of th is distinct TXA(2)- and collagen-sensitive PLA(2) involves two steps: (a) sustained elevation of cytosolic Ca2+ coupled to the influx of ext racellular Ca2+; and (b) interaction with agonists such as TXA(2) and collagen.