酪氨酸激酶抑制剂染料木黄酮可直接抑制γ-氨基丁酸A型（GABAA）受体。

The tyrosine kinase inhibitor genistein directly inhibits GABAA receptors.

作者信息

Huang R Q, Fang M J, Dillon G H

机构信息

Department of Pharmacology, University of North Texas, Health Science Center at Fort Worth, 3500 Camp Bowie Blvd., Fort Worth, TX 76107, USA.

出版信息

Brain Res Mol Brain Res. 1999 Apr 6;67(1):177-83. doi: 10.1016/s0169-328x(99)00061-3.

DOI:10.1016/s0169-328x(99)00061-3

PMID:10101245

Abstract

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.

摘要

蛋白酪氨酸激酶（PTK）抑制剂染料木黄酮已被广泛用于研究酪氨酸磷酸化对神经递质功能的潜在影响。我们在此报告，染料木黄酮通过直接作用抑制GABAA受体。即使染料木黄酮在细胞内溶液中预先平衡，将其与GABA在细胞外应用时，也能可逆地抑制从表达大鼠α1β2γ2S或α1β2受体的HEK293细胞记录到的GABA激活电流。大豆苷元是染料木黄酮的类似物，不阻断PTK，但也能抑制GABA激活电流。PTK的特异性抑制剂拉芬司汀A与GABA共同应用时，对GABA反应没有影响。我们的结果表明，染料木黄酮对GABAA受体具有直接抑制作用，且该作用不是通过抑制酪氨酸激酶介导的。