Inhibition of Na+, K+ -ATPase Activity by Phospholipase A2 and Several Lysophospholipids: Possible Role of Phospholipase A2 in Noradrenaline Release from Cerebral Cortical Synaptosomes

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Abstract
P-Bromophenacyl bromide (PBPB), quinacrine and indomethacin, which inhibit phospholipase A2 (PLA2; EC 3.1.1.4) activity in several tissues, caused a dose-dependent inhibition of prelabelled [3H]noradrenaline ([3H]NA) release evoked by high concentrations of K+ from rat cerebral cortical synaptosomes. Release of prelabelled [3H]NA was caused by natural lysophosphatidic acid (LPA; 10−6-10−5 gmL−1) and lysophosphatidylcholine (LPC; 10−6-10−5 g mL−1) and synthetic LPA (6 × 10−6, 2 × 10−5 M) and LPC (6 × 10−6, 2 × 10−5 M), but not by natural lysophosphatidylserine (LPS; 10−5 g mL−1), lysophosphatidylethanolamine (LPE; 10−5 g mL−1) and lysophosphatidylinositol (LPI; 10−5 g mL−1). The release evoked by natural LPA and LPC could be inhibited only marginally by PBPB and quinacrine. Phosphatidic acid (PA)-specific and phosphatidylcholine (PC)-specific PLA2 activities from rat cerebral cortical synaptosomes were stimulated in incubation medium containing high concentrations of K+ or calcium ionophore A23187. Low concentrations of PLA2 (10−6–10−8 g mL−1, from bee venom) inhibited the synaptic membrane Na+, K+-ATPase activity in incubation media with intracellular levels of free Ca2+. Several lysophospholipids (LPLs), metabolites of the PLA2 type, also inhibited the synaptic membrane Na+, K+-ATPase activity in a dose-dependent manner. The minimum effective concentrations of natural LPA, LPC, LPS, LPI and LPE were 10−6, 4·7 × 10−6, 10−5,4·7 × 10−5 and 4·7 × 10−5 g mL−1, respectively. These results suggest that PLA2 and/or its metabolites, LPLs, especially LPA and LPC, may play partial roles in the depolarization and/or release of noradrenaline through their inhibitory action on the Na+, K+-ATPase activity in the brain.

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