Enhancement of arachidonic acid release and prostaglandin F-2 alpha formation by Na3VO4 in PC12 cells and GH3 cells

Both activation of phospholipase A(2) causing arachidonic acid release and tyrosine phosphorylation have been proposed to be involved in neuronal func tions. Previously, we reported that orthovanadate (Na3VO4), an inhibitor of tyrosine phosphatases, stimulated tyrosine phosphorylation in proteins and enhanced Ca2+-induced noradrenaline release in rat pheochromocytoma PC12 c ells. However, the role of tyrosine phosphorylation on phospholipase A(2) a ctivity and/or arachidonic acid release in neuronal cells has not been well established. The effects of Na3VO4 on arachidonic acid release and prostag landin F-2 alpha formation were investigated in two types of neuronal cell lines. In PC12, cells, addition of Na3VO4 stimulated [H-3]arachidonic acid release and prostaglandin F-2 alpha formation in a concentration-dependent manner. Co-addition of 5 mM Na3VO4 enhanced ionomycin-stimulated [H-3]arach idonic acid release. Na3VO4 also enhanced ionomycin-stimulated [H-3]arachid onic acid release from GH3 cells, a clonal strain from rat anterior pituita ry. These findings suggest that the tyrosine phosphorylation pathway regula tes arachidonic acid release by phospholipase A(2) and prostaglandin F-2 al pha formation in neuronal cells. (C) 2001 Elsevier Science B.V. All rights reserved.