Phospholipase activity in permeabilized platelets: evidence that pla2, plc and pld are not essential to exocytosis. Coorssen, Jens R. Department of Pathology, McMaster University, Hamilton, Ontario, Canada L8N 3Z5
APStracts 2:0395C, 1995.
Numerous studies have identified phospholipase metabolites as membrane fusogens, and phospholipase D (PLD) (Coorssen and Haslam, FEBS Lett. 316: 170-174, 1993), C (PLC) and A2 (PLA2) activities correlate with secretion. Do these enzymes have essential or modulatory roles? This study confirms that secretion does not require Ca2+ or PLC (Coorssen et al., Cell Regulation 1: 1027-1041, 1990). Arachidonic acid (AA), phosphatidic acid (PA) or analogues, exogenous metabolites of PLA2 and PLD, were tested in electropermeabilized human platelets. AA potentiated GTP[tau]S-induced secretion; eicosanoids were not essential. Endogenous [3H]AA formation correlated with GTP[tau]S -induced secretion, and PMA promoted these effects. Inhibitors were used to probe phospholipase influences on secretion. Only PLD inhibitors blocked secretion. However, PMA blocked inhibition of PKC and secretion by quercetin suggesting that PA formed by PLD supports PKC activation and GTP[tau]S-induced secretion. Thus, PA analogues had no effect alone but enhanced GTP[tau]S-induced PKC activity and secretion. Slower PLD activation compared to secretion also indicates a nonessential role. This is the first report of a Ca2+-independent PLA2 activity in human platelets, use of quercetin as a PLD inhibitor, and dissociation of PLA2, PLC and PLD activities from secretion. No major phospholipase activities are essential to the final steps in exocytosis but modulatory roles are indicated.

Received 27 June 1995; accepted in final form 27 October 1995.
APS Manuscript Number C378-5.
Article publication pending Am. J. Physiol. (Cell Physiology).
ISSN 1080-4757 Copyright 1995 The American Physiological Society.
Published in APStracts on 30 November 95