Tetrandrine: a new ligand to block voltage-dependent Ca2+ and Ca(+)-activated K+ channels.
Tetrandrine: a new ligand to block voltage-dependent Ca2+ and Ca(+)-activated K+ channels.
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DOI：
10.1016/0024-3205(94)00952-x
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发表时间：
1994-12
期刊：
影响因子：
6.1
通讯作者：
Gang Wang;JoséR. Lemos
中科院分区：
文献类型：
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作者：
Gang Wang;JoséR. Lemos
汉防已碱是一种传统的药用生物碱，本文综述了其药理学研究进展。汉防己甲素在中国临床上用于治疗多种疾病已有数百年的历史。最近的一系列研究揭示了其多种药理和治疗作用的主要机制。粉防己碱是一种新型的电压激活L型Ca ~（2+）通道阻滞剂，在多种可兴奋细胞如心肌细胞、GH_（3+）垂体前叶细胞、神经母细胞瘤细胞以及大鼠神经突神经末梢中均有发现。虽然粉防己碱不属于三种经典钙通道阻滞剂中的任何一种，但电生理和放射配体结合研究表明粉防己碱是一种L型钙通道阻滞剂，其结合位点位于通道α1亚基上的苯并硫氮卓受体。此外，粉防己碱是电压依赖性T型Ca 2+通道的阻断剂。很明显，粉防己碱在治疗心血管疾病，包括高血压和室上性心律失常中的作用主要是由于其阻断电压激活的L型和T型Ca 2+通道。此外，该生物碱是神经垂体神经末梢的Ca 2+激活的K+（K（Ca））通道的有效阻断剂。粉防己碱对K（Ca）通道的阻断动力学与典型的K（Ca）通道阻断剂如四乙基铵和Ba ~（2+）的阻断动力学有很大不同。汉防己甲素作为K（Ca）通道阻滞剂的临床作用尚不清楚，但它是研究K（Ca）通道功能的一个很有前途的配体。
Extensive pharmacological investigations on tetrandrine, one of the traditional medicinal alkaloids, are reviewed. Tetrandrine has been used clinically in China for centuries in the treatment of many diseases. A recent series of studies has revealed major mechanisms underlying its multiple pharmacological and therapeutic actions. One of the most interesting discoveries is that tetrandrine is a new kind blocker of the voltage-activated, L-type Ca2+channel in a variety of excitable cells, such as cardiac, GH3anterior pituitary and neuroblastoma cells, as well as in rat neuropophysial nerve terminals. Although tetrandrine does not belong to any of the three classical Ca2+channel blocker groups, electrophysiological and radioligand binding studies show that tetrandrine is an L-type Ca2+channel blocker with its binding site located at the benzothiazepine receptor on theα1-subunit of the channel. In addition, tetrandrine is a blocker of the voltage-dependent T-type Ca2+channel. It is clear that tetrandrine's actions in the treatment of cardiovascular diseases, including hypertension and supraventricular arrhythmia, are due primarily to its blocking of voltage-activated L-type and T-type Ca2+channels. Furthermore, this alkaloid is a potent blocker of the Ca2+-activated K+(K(Ca)) channels of neurohypophysial nerve terminals. The blocking kinetics of tetrandrine on the K(Ca)channel is quite different from that of typical K(Ca)channel blockers such as tetraethylammonium and Ba2+. Although the clinical role of tetrandrine as a blocker of the K(Ca)channels is unclear, it is a promising ligand for the study of K(Ca)channel function.