Inhibition of vascular smooth muscle cell K+ currents by tyrosine kinase inhibitors genistein and ST 638.
Inhibition of vascular smooth muscle cell K+ currents by tyrosine kinase inhibitors genistein and ST 638.
复制标题
酪氨酸激酶抑制剂金雀异黄素和 ST 638 对血管平滑肌细胞 K 电流的抑制。
作者：
S. Smirnov;P. Aaronson
用全细胞膜片钳技术研究了几种酪氨酸激酶抑制剂对大鼠和兔肺动脉细胞电压门控性钾电流(IK)的影响。金雀异黄素(20~100mumol/L)和ST638(0.5~40mumol/L)以剂量依赖方式阻断IK，但不能被失活的染料木素类似物地黄素(100mumol/L)阻断。当从贴片移液管中排除三磷酸腺苷或被劣质酪氨酸激酶底物三磷酸腺苷-伽马-S取代时，这种抑制作用没有明显改变。酪氨酸磷酸酶抑制剂原钒酸盐加入浴液(0.5 mm ol/L)或移液管(0.2 mm o l/L)也不影响抑制作用。在大鼠中，IK通常在300ms后失活，可以忽略不计。在10moMol/L ST638作用下，Ik在去极化后约5ms达到峰值(+60 mV)，然后显著衰减。在兔中，IK表现出显著的快速衰减的初始成分，但仅被ST 638轻微抑制，ST 638优先阻断持续电流；金雀异黄素表现出相反的选择性。这些观察结果表明，金雀异黄素和ST 638对IK的阻断不是通过抑制酪氨酸激酶活性来实现的，进一步表明在这两种细胞中，Genistein和ST 638分别优先阻断快速和缓慢失活的IK组分。
The whole-cell patch-clamp technique was used to characterize the effects of several tyrosine kinase inhibitors on the voltage-gated K+ current (IK) in rat and rabbit pulmonary artery cells. IK was blocked in a dose-dependent manner by genistein (20 to 100 mumol/L) and ST 638 (0.5 to 40 mumol/L) but not by the inactive genistein analogue diadzein (100 mumol/L). This inhibition was not significantly altered when ATP was excluded from the patch pipette or when it was replaced by the poor tyrosine kinase substrate ATP-gamma-S. The inhibition was also unaffected by inclusion of the tyrosine phosphatase inhibitor orthovanadate in either the bath (0.5 mmol/L) or pipette (0.2 mmol/L) solutions. In the rat, IK ordinarily inactivated negligibly over 300 ms. In the presence of 10 mumol/L ST 638, however, IK reached a peak approximately 5 ms after depolarization (to +60 mV) and then decayed markedly. In the rabbit, IK demonstrated a prominent rapidly decaying initial component that was only slightly inhibited by ST 638, which preferentially blocked the sustained current; genistein showed the opposite selectivity. These observations indicated that IK blockade by genistein and ST 638 was not mediated by an inhibition of tyrosine kinase activity and further suggested that in both types of cells genistein and ST 638 preferentially blocked rapidly and slowly inactivating components of IK, respectively.
磷脂酶 C 的酪氨酸磷酸化伴随着人 B 细胞系中血小板激活因子的激活。
DOI：
--
发表时间：
1993
期刊：
Journal of immunology (Baltimore, Md. : 1950)
影响因子：
--
作者：
Kuruvilla,A;Putcha,G;Poulos,E;Shearer,WT
通讯作者：
Shearer,WT
钒酸盐抑制膜磷酸酪氨酰蛋白磷酸酶活性。
DOI：
10.1016/0006-291x(82)90635-0
发表时间：
1982
影响因子：
3.1
作者：
Swarup,G;Cohen,S;Garbers,DL
通讯作者：
Garbers,DL