The tyrosine kinase inhibitor genistein directly inhibits GABA(A) receptors

The protein tyrosine kinase (PTK) inhibitor genistein has been widely used to examine potential effects of tyrosine phosphorylation on neurotransmitte r function. We report here that genistein inhibits GABA(A) receptors throug h a direct effect. Extracellular application of genistein and GABA reversib ly inhibited GABA-activated currents recorded from HEK293 cells expressing rat alpha 1 beta 2 gamma 2S or alpha 1 beta 2 receptors, even when genistei n was preequilibrated in the intracellular solution. Daidzein, an analog of genistein that does not block PTK, also inhibited GABA-activated current. Coapplication of lavendustin A, a specific inhibitor of PTK, had no effect on the GABA response. Our results demonstrate that genistein has a direct i nhibitory effect on GABA(A) receptors that is not mediated via inhibition o f tyrosine kinase. (C) 1999 Elsevier Science B.V. All rights reserved.