Enhancement of arachidonic acid release and prostaglandin F2α 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 functions. 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 cells. However, the role of tyrosine phosphorylation on phospholipase A(2) activity and/or arachidonic acid release in neuronal cells has not been well established. The effects of Na3VO4 on arachidonic acid release and prostaglandin 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]arachidonic acid release. Na3VO4 also enhanced ionomycin-stimulated [H-3]arachidonic acid release from GH3 cells, a clonal strain from rat anterior pituitary. These findings suggest that the tyrosine phosphorylation pathway regulates arachidonic acid release by phospholipase A(2) and prostaglandin F-2 alpha formation in neuronal cells. (C) 2001 Elsevier Science B.V. All rights reserved.