Effects of bilobalide on gamma-aminobutyric acid levels and glutamic acid decarboxylase in mouse brain

We have previously demonstrated that bilobalide, a constituent of the Ginkg o biloba extract, possesses anticonvulsant activity, and suggested that the mechanism of its anticonvulsant action involves modulation of gamma-aminob utyric acid (GABA)-related neuronal transmission. This study examined the e ffects of bilobalide on the level of GABA and glutamate, the activity and t he amount of glutamic acid decarboxylase (EC 4.1.1.15), and the function of GABA(A) receptors in the hippocampus, cerebral cortex and striatum of the mouse. GABA levels, glutamic acid decarboxylase activity, and the protein a mount of 67 kDa glutamic acid decarboxylase in the hippocampus of mice trea ted with bilobalide (30 mg/kg, p.o., once a day for 4 days) were significan tly higher than those in controls. However, there were no significant diffe rences in glutamate levels or, the number and the dissociation constants of GABA(A) receptors in the hippocampus between control and bilobalide-treate d mice. These results suggest that the anticonvulsant effect of bilobalide is due to elevation of GABA levels, possibly through potentiation of glutam ic acid decarboxylase activity and enhancement of the protein amount of 67 kDa glutamic acid decarboxylase by bilobalide. (C) 1999 Elsevier Science B. V. All rights reserved.