Yuichi Tomori

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

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.