Sodium valproate stimulates the particulate form of glutamine synthetase in rat brain

The anticonvulsant drug, sodium valproate, enhanced total activity of glutamine synthetase in cortical and cerebellar homogenates of the rat at concentrations of 25-50 mM, without significantly altering substrate affinity. This effect was due to a selective increase in the Vmax and substrate affinity of the enzyme in the particulate fraction. At the same concentration the drug caused little change in the Vmax of the cytosolic enzyme, although the substrate affinity was reduced. These effects cannot be attributed to isozymes of glutamine synthetase as only one form could be demonstrated by ion-exchange chromatography or electroblotting with antibodies to glutamine synthetase. This selective stimulation of particulate glutamine synthetase is suggested to be due to increases in membrane fluidity induced by the drug. The contribution of these effects to the mechanistic action of sodium valproate is discussed.