Huang R Q, Dillon G H
Department of Pharmacology, University of North Texas Health Science Center, 3500 Camp Bowie Blvd, Fort Worth, TX 76107, USA.
Neuropharmacology. 2000 Aug 23;39(11):2195-204. doi: 10.1016/s0028-3908(00)00046-0.
Genistein, a tyrosine kinase inhibitor, has been widely used to examine potential effects of protein tyrosine kinase (PTK)-mediated regulation of receptor/channel function. Alteration of ion channel function in the presence of genistein has typically led to the conclusion that PTK regulates the activity of the channel under investigation. In the present report, we have assessed the possibility that genistein directly inhibits the glycine receptor, independent of effects on protein tyrosine kinase. Coapplication of genistein with glycine reversibly inhibited the strychnine-sensitive, glycine-activated current recorded from hypothalamic neurons. The time course of genistein action was rapid (within ms). Equilibration of genistein in the intracellular solution did not affect the ability of extracellularly applied genistein to inhibit the glycine response. Glycine concentration-response profiles generated in the absence and presence of genistein indicated the block was due to non-competitive antagonism. The genistein effect also displayed voltage-dependence. Daidzein, an analog of genistein that does not block protein kinases, also inhibited glycine-activated current. Coapplication of lavendustin A, a specific inhibitor of PTK, had no effect on the glycine response. Our results demonstrate that the tyrosine kinase inhibitor genistein has a direct inhibitory effect on glycine receptors that is not mediated via inhibition of PTK.
染料木黄酮是一种酪氨酸激酶抑制剂，已被广泛用于研究蛋白酪氨酸激酶（PTK）介导的受体/通道功能调节的潜在作用。在染料木黄酮存在的情况下，离子通道功能的改变通常会得出PTK调节所研究通道活性的结论。在本报告中，我们评估了染料木黄酮直接抑制甘氨酸受体的可能性，这与对蛋白酪氨酸激酶的影响无关。染料木黄酮与甘氨酸共同应用可逆地抑制了从下丘脑神经元记录到的对士的宁敏感的、甘氨酸激活的电流。染料木黄酮作用的时间进程很快（在毫秒内）。染料木黄酮在细胞内溶液中的平衡并不影响细胞外应用的染料木黄酮抑制甘氨酸反应的能力。在不存在和存在染料木黄酮的情况下产生的甘氨酸浓度-反应曲线表明，这种阻断是由于非竞争性拮抗作用。染料木黄酮的作用也表现出电压依赖性。大豆苷元是染料木黄酮的一种类似物，它不阻断蛋白激酶，也抑制甘氨酸激活的电流。PTK的特异性抑制剂拉文达ustin A共同应用对甘氨酸反应没有影响。我们的结果表明，酪氨酸激酶抑制剂染料木黄酮对甘氨酸受体有直接抑制作用，这种作用不是通过抑制PTK介导的。
