Enhancement of arachidonic acid release and prostaglandin F(2alpha) formation by Na3VO4 in PC12 cells and GH3 cells.
Both activation of phospholipase A2 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 A2 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(2alpha) formation were investigated in two types of neuronal cell lines. In PC12 cells, addition of Na3VO4 stimulated [3H]arachidonic acid release and prostaglandin F(2alpha) formation in a concentration-dependent manner. Co-addition of 5 mM Na3VO4 enhanced ionomycin-stimulated [3H]arachidonic acid release. Na3VO4 also enhanced ionomycin-stimulated [3H]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 A2 and prostaglandin F(2alpha) formation in neuronal cells.
Mori
A
A
Department of Pharmacology, Graduate School of Pharmaceutical Sciences, Hokkaido University, 060-0812, Sapporo, Japan.
Yasuda
Y
Y
Murayama
T
T
Nomura
Y
Y
D000818:Animals; D016718:Arachidonic Acid / Q000378:metabolism*; D002614:Chelating Agents / Q000494:pharmacology; D003600:Cytosol / Q000201:enzymology; D015237:Dinoprost / Q000378:metabolism*; D004305:Dose-Response Relationship, Drug; D004357:Drug Synergism; D004533:Egtazic Acid / Q000031:analogs & derivatives / Q000494:pharmacology; D006861:Hydrogen Peroxide / Q000494:pharmacology; D036341:Intercellular Signaling Peptides and Proteins; D015759:Ionomycin / Q000494:pharmacology; D016716:PC12 Cells; D010455:Peptides; D010741:Phospholipases A / Q000378:metabolism; D054467:Phospholipases A2; D051381:Rats; D014407:Tumor Cells, Cultured / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D014638:Vanadates / Q000494:pharmacology*; D014862:Wasp Venoms / Q000494:pharmacology
D002614:Chelating Agents; D036341:Intercellular Signaling Peptides and Proteins; D010455:Peptides; D014862:Wasp Venoms; C070379:1,2-bis(2-aminophenoxy)ethane N,N,N',N'-tetraacetic acid acetoxymethyl ester; D016718:Arachidonic Acid; D014638:Vanadates; D004533:Egtazic Acid; D015759:Ionomycin; C037500:mastoparan; D015237:Dinoprost; D006861:Hydrogen Peroxide; D010741:Phospholipases A; D054467:Phospholipases A2