Nakaya Yutaka, Mawatari Kazuaki, Takahashi Akira, Harada Nagakatsu, Hata Akiko, Yasui Sonoko
Department of Nutrition and Metabolism, Institute of Health Biosciences, The University of Tokushima Graduate School, Tokushima, Japan.
J Med Invest. 2007 Aug;54(3-4):381-4. doi: 10.2152/jmi.54.381.
In vascular smooth muscle cells, large-conductance Ca(2+)-activated K(+) channels (K(Ca) channels) play a pivotal role in determining membrane potential, and thereby the vascular tone. Ginsenoside Re, a phytochemical from ginseng, is reported to activate this channel, but its precise mechanism is unsolved. Patch clamp studies showed that ginsenoside Re activates K(Ca) channels in the arterial smooth muscle cell line A10 in a dose-dependent manner. The channel-opening effect of ginsenoside Re was inhibited by 1 microM L-NIO, an inhibitor of eNOS, but not by 3 microM SMTC, an inhibitor of nNOS, indicating that ginsenoside Re activated K(Ca) channels through activation of eNOS. SH-6 (10 microM), an Akt inhibitor, and wortmannin, a PI3-kinase inhibitor, completely blocked activation of K(Ca) channels by ginsenoside Re, indicating that it activates eNOS via a c-Src/PI3-kinase/Akt-dependent mechanism. In addition, the ginsenoside Re-induced activation of eNOS and K(Ca) channel was blocked by 10 microM ICI 182, 780, an inhibitor of membrane estrogen receptor-alpha, suggesting that eNOS activation occurs via a non-genomic pathway of this receptor. In conclusion, ginsenoside Re releases NO via a membrane sex steroid receptors, resulting in K(Ca) channel activation in vascular smooth muscle cells, promoting vasodilation and preventing severe arterial contraction.
在血管平滑肌细胞中，大电导钙激活钾通道（K（Ca）通道）在决定膜电位进而决定血管张力方面起着关键作用。人参中的一种植物化学物质人参皂苷Re据报道可激活该通道，但其确切机制尚未解决。膜片钳研究表明，人参皂苷Re以剂量依赖性方式激活动脉平滑肌细胞系A10中的K（Ca）通道。人参皂苷Re的通道开放作用被eNOS抑制剂1 microM L-NIO抑制，但未被nNOS抑制剂3 microM SMTC抑制，这表明人参皂苷Re通过激活eNOS激活K（Ca）通道。Akt抑制剂SH-6（10 microM）和PI3激酶抑制剂渥曼青霉素完全阻断了人参皂苷Re对K（Ca）通道的激活，表明它通过c-Src/PI3激酶/Akt依赖性机制激活eNOS。此外，人参皂苷Re诱导的eNOS和K（Ca）通道激活被膜雌激素受体α抑制剂10 microM ICI 182,780阻断，这表明eNOS激活是通过该受体的非基因组途径发生的。总之，人参皂苷Re通过膜性甾体激素受体释放NO，导致血管平滑肌细胞中的K（Ca）通道激活，促进血管舒张并防止严重的动脉收缩。
