科研之友
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摘要
Puerarin is the main isoflavone found in Pueraria lobata (Willd) Ohwi, which has been used in therapy for various cardiovascular diseases. The present study examined the effects of puerarin on the large-conductance voltage- and Ca2+-activated potassium (BKCa) channel and on rat thoracic aortas. BKCa channels encoded with either alpha(BK-alpha) or alpha/beta subunits (BK-alpha+beta 1) were heterologously expressed in Xenopus oocytes or human embryonic kidney 293 cells. The activities of BKCa channels were measured using excised patch- clamp recordings. Puerarin activated BK-alpha+beta 1 currents with a half-maximal concentration (EC50) of 0.8 nM and a Hill coefficient of 1.11 at 10 mu M Ca2+ and with an EC50 of 12.6 nM and a Hill coefficient of 1.08 at 0 mu M Ca2+. Puerarin (1 nM) induced a 16-mV leftward shift in the conductance-voltage curve for BK-alpha+beta 1 currents 10 mu M Ca2+ and at 100 nM induced a 26-mV leftward shift at 0 mu M Ca2+. Puerarin mainly increased the BK-alpha+beta 1 channel open probability without changing the unitary conductance. Activation was also detected in the absence of the beta 1 subunit. A deglycosylated analog of puerarin, daidzein, also activated BKCa channels with weaker potency. In addition, puerarin (0.1 to 1000 mu M) caused concentration- dependent relaxations of rat thoracic aortic rings contracted with 1 mu M noradrenaline bitartrate (EC50 = 1.1 mu M). These were significantly inhibited by 50 nM iberiotoxin, a specific blocker of BKCa channels. This is the first study demonstrating that puerarin activates BKCa channels, especially BK-alpha+beta 1 channels. The activation of the BKCa channel probably contributes to the puerarin-mediated vasodilation action.
- 出版日期2007-10
- 单位华中科技大学
