Endothelin-1 and insulin activate the steady-state voltage dependent R-type Ca2+ channel in aortic smooth muscle cells via a pertussis toxin and cholera toxin sensitive G-protein
Endothelin-1 and insulin activate the steady-state voltage dependent R-type Ca2+ channel in aortic smooth muscle cells via a pertussis toxin and cholera toxin sensitive G-protein
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DOI：
10.1023/a:1006887714302
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发表时间：
1998-06-01
影响因子：
4.3
通讯作者：
Pothier, P
中科院分区：
文献类型：
--
作者：
Bkaily, G;Naik, R;Pothier, P
在单个兔主动脉平滑肌细胞上，内皮素-1(10(-7)M)和胰岛素(80mU/ml)可通过激活稳态电压依赖性R型钙通道而最大限度地诱导细胞内钙离子持续升高，而百日咳毒素(PTX)、霍乱毒素(CTX)或清除细胞外钙离子均可显著降低细胞内游离钙离子([Ca](I))水平。PTX和CTX均不能抑制持续去极化引起的持续性钙内流和通过激活R型钙通道而引起的[Ca](I)升高。此外，选择性蛋白激酶C抑制剂双吲哚马来酰亚胺或L型钙通道特异性阻断剂硝苯地平不能减弱ET-1和胰岛素引起的钙内流持续增加，但可被R型钙通道阻滞剂(-)PN200-110(伊拉地平)完全逆转。这些结果提示，胰岛素和ET-1均可激活兔VSMC上硝苯地平不敏感但伊拉地平敏感的稳态电压依赖性R型钙通道，这些通道与甲氨蝶呤和环磷酰胺敏感的G蛋白(S)直接偶联。
In single rabbit aortic smooth muscle cells, and at a concentration known to induce a maximum sustained increase of intracellular Ca2+ via activation of the steady-state voltage dependent R-type Ca2+ channels, endothelin-1 (10(-7) M) and insulin (80 mu U/ml) were found to induce a sustained increase in cytosolic free Ca2+ ([Ca](i)) levels that was significantly attenuated by pre-treatment with either pertussis toxin (PTX), cholera toxin (CTX) or removal of extracellular Ca2+.However, both PTX and CTX failed to inhibit the sustained depolarization-evoked sustained Ca2+ influx and [Ca](i) elevation via activation of the R-type Ca2+ channels. Moreover, ET-1 and insulin-evoked sustained increases in Ca2+ influx were not attenuated by the selective PKC inhibitor, bisindolylmaleimide (BIS), or the specific L-type Ca2+ channel blocker, nifedipine, but were completely reversed by the R-type Ca2+ channel blocker, (-) PN 200-110 (isradipine). These data suggest that both insulin and ET-1 activate the nifedipine-insensitive but isradipine-sensitive steady state voltage dependent R-type Ca2+ channels present on rabbit VSMCs and these channels are directly coupled to PTX and CTX sensitive G protein(s).