Effect of vanadate on brain protein phosphorylation.
The effect of vanadate on the phosphorylation of synaptosomal membrane proteins prepared from rat cerebral cortex was studied. Vanadate concentrations of 10(-6), 10(-5), and 10(-4) M increased the endogenous phosphorylation activity by 25%, 37%, and 75%, respectively. Increasing the ATP concentration in the assay medium from 50 to 500 microM did not influence the above effect. A commercial preparation of the purified protein kinase was stimulated 40% by 10(-3) M vanadate. Calcium-calmodulin dependent activity was stimulated only 20% by 10(-5) M vanadate. The effect was not enhanced by further increasing vanadate concentration. Addition of calcium ions (above 50 microM) suppressed the vanadate effect, while an inhibition was observed at high Ca2+ concentration (2.5 mM). Below 50 microM calcium ions stimulated phosphorylation activity in the absence of vanadate and did not affect the stimulatory action of vanadate. Cyclic AMP-dependent endogenous phosphorylation was also stimulated by vanadate. Activation by cAMP could not be observed at vanadate concentrations above 10(-6) M. Possible mechanisms of the vanadate effect are discussed.
D000818:Animals; D001921:Brain / Q000187:drug effects* / Q000201:enzymology; D002118:Calcium / Q000502:physiology; D000242:Cyclic AMP / Q000502:physiology; D008297:Male; D009419:Nerve Tissue Proteins / Q000378:metabolism; D010766:Phosphorylation; D010770:Phosphotransferases / Q000378:metabolism*; D011494:Protein Kinases / Q000378:metabolism; D051381:Rats; D013570:Synaptic Membranes / Q000187:drug effects / Q000378:metabolism; D013574:Synaptosomes / Q000187:drug effects / Q000378:metabolism; D014638:Vanadates; D014639:Vanadium / Q000494:pharmacology*
D009419:Nerve Tissue Proteins; D014639:Vanadium; D014638:Vanadates; D000242:Cyclic AMP; D010770:Phosphotransferases; D011494:Protein Kinases; D002118:Calcium