The tyrosine kinase inhibitor genistein directly inhibits GABAA receptors.
The protein tyrosine kinase (PTK) inhibitor genistein has been widely used to examine potential effects of tyrosine phosphorylation on neurotransmitter function. We report here that genistein inhibits GABAA receptors through a direct effect. Extracellular application of genistein and GABA reversibly inhibited GABA-activated currents recorded from HEK293 cells expressing rat alpha1beta2gamma2S or alpha1beta2 receptors, even when genistein 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 inhibitory effect on GABAA receptors that is not mediated via inhibition of tyrosine kinase.
Huang
R Q
RQ
Department of Pharmacology, University of North Texas, Health Science Center at Fort Worth, 3500 Camp Bowie Blvd., Fort Worth, TX 76107, USA.
Fang
M J
MJ
Dillon
G H
GH
D000818:Animals; D001921:Brain / Q000201:enzymology; D001923:Brain Chemistry / Q000187:drug effects*; D002478:Cells, Cultured; D004791:Enzyme Inhibitors / Q000494:pharmacology*; D004968:Estrogens, Non-Steroidal / Q000494:pharmacology; D058787:GABA-A Receptor Antagonists; D015870:Gene Expression / Q000502:physiology; D019833:Genistein / Q000494:pharmacology*; D006801:Humans; D007529:Isoflavones / Q000494:pharmacology; D007668:Kidney / Q000166:cytology; D008564:Membrane Potentials / Q000187:drug effects / Q000502:physiology; D018408:Patch-Clamp Techniques; D010636:Phenols / Q000494:pharmacology; D011505:Protein-Tyrosine Kinases / Q000037:antagonists & inhibitors*; D051381:Rats; D011994:Recombinant Proteins; D005680:gamma-Aminobutyric Acid / Q000494:pharmacology
D004791:Enzyme Inhibitors; D004968:Estrogens, Non-Steroidal; D058787:GABA-A Receptor Antagonists; D007529:Isoflavones; D010636:Phenols; D011994:Recombinant Proteins; C062898:lavendustin A; D005680:gamma-Aminobutyric Acid; C004742:daidzein; D019833:Genistein; D011505:Protein-Tyrosine Kinases