Phospholipase activation and secretion: Evidence that PLA(2), PLC, and PLD are not essential to exocytosis

被引:29
作者
Coorssen, JR [1 ]
机构
[1] MCMASTER UNIV, DEPT PATHOL, HAMILTON, ON L8N 3Z5, CANADA
来源
AMERICAN JOURNAL OF PHYSIOLOGY-CELL PHYSIOLOGY | 1996年 / 270卷 / 04期
关键词
arachidonic acid; GTP-binding protein; phosphatidic acid; platelet; protein kinase C;
D O I
10.1152/ajpcell.1996.270.4.C1153
中图分类号
Q2 [细胞生物学];
学科分类号
071009 ; 090102 ;
摘要
Numerous studies have identified phospholipase metabolites as membrane fusogens, and phospholipase D (PLD) (J. R. Coorssen and R. J. Haslam. FEBS Lett. 316: 170-174, 1993), C (PLC), and A(2) (PLA(2)) 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 Regul. 1: 1027-1041, 1990). Arachidonic acid (AA), phosphatidic acid (PA) and analogues, exogenous metabolites of PLA(2) and PLD, were tested in electropermeabilized human platelets. AA potentiated guanosine 5'-O-(3-thiotriphosphate) (GTP gamma S)-induced secretion, and eicosanoids were not essential. Endogenous [H-3]AA formation correlated with GTP gamma S-induced secretion, and phorbol 12-myristate 13-acetate (PMA) promoted these effects. Inhibitors were used to probe phospholipase influences on secretion. Only PLD inhibitors blocked secretion. However, PMA blocked inhibition of protein kinase C (PKC) and secretion by quercetin, suggesting that PA formed by PLD supports PKC activation and GTP gamma S-induced secretion. Thus PA analogues had no effect alone but enhanced GTP gamma S-induced PKC activity and secretion. Slower PLD activation compared with secretion also indicates a nonessential role. This is the first report of a Ca2+-independent PLA(2) activity in human platelets, use of quercetin as a PLD inhibitor, and dissociation of PLA(2), PLC, and PLD activities from secretion. No major phospholipase activities are essential to the final steps in exocytosis, but modulatory roles are indicated.
引用
收藏
页码:C1153 / C1163
页数:11
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