Department of Physiology, Guangzhou Medical University, 195 Dongfeng West Road, Guangzhou 510182, People's Republic of China.
Mol Cell Biochem. 2012 Jul;366(1-2):149-57. doi: 10.1007/s11010-012-1292-0. Epub 2012 Apr 4.
In the earlier study, sodium orthovanadate (SOV) has been reported to be a powerful inhibitor of (Na(+), K(+)) adenosine triphosphatase, exhibit widespread actions on the renal and cardiovascular systems, induces smooth muscle contraction by inhibiting the phosphorylation of the protein tyrosine phosphatases. In the current study, we aimed to investigate the cellular mechanisms by which SOV facilitated contractile response of vas deferens smooth muscle and its potential therapeutic advantage. Exogenous application of ATP and NA-caused contraction was strengthened by pretreatment with SOV. This facilitation was inhibited not by bath with the inhibitor of P2 receptor, PPADS, or the inhibitor of α1 receptor, Prazosin, but by bath with the protein tyrosine kinase inhibitor, Genistein. SOV induced a sustained increase in intracellular Ca(2+) of smooth muscle cells, which was abolished by 100 μM Genistein or Ca(2+)-free solution. The facilitation of SOV could also be inhibited by the selective inhibitors of TRP channel, 2-APB and non-selective cation channel, Gd(3+), Ni(+). The in vivo study showed that peritoneal injection of SOV in dystrophic mice (mdx mice) enhanced the contraction of vas deferens smooth muscle stimulated by electrical field stimulation, ATP, noradrenaline, or KCl. The above results suggest that SOV facilitates the concentration of vas deferens smooth muscle through the tyrosine phosphorylation activated the non-selective cation channels, which has potential use in the therapy for muscle dysfunction.
在之前的研究中，正钒酸钠（SOV）已被报道为（Na(+), K(+))三磷酸腺苷酶的强有力抑制剂，对肾脏和心血管系统有广泛的作用，通过抑制蛋白质酪氨酸磷酸酶的磷酸化来诱导平滑肌收缩。在本研究中，我们旨在研究 SOV 促进输精管平滑肌收缩反应的细胞机制及其潜在的治疗优势。用 SOV 预处理可增强外源性 ATP 和 NA 引起的收缩。这种促进作用不受 P2 受体抑制剂 PPADS 或 α1 受体抑制剂 Prazosin 的浴液抑制，但受蛋白酪氨酸激酶抑制剂 Genistein 的浴液抑制。SOV 诱导平滑肌细胞内 Ca(2+)持续增加，100 μM Genistein 或无 Ca(2+)溶液可消除这种增加。TRP 通道的选择性抑制剂 2-APB 和非选择性阳离子通道的抑制剂 Gd(3+)、Ni(+)也能抑制 SOV 的促作用。体内研究表明，腹腔注射 SOV 可增强肌营养不良症（mdx 小鼠）小鼠输精管平滑肌对电刺激、ATP、去甲肾上腺素或 KCl 刺激的收缩。上述结果表明，SOV 通过酪氨酸磷酸化激活非选择性阳离子通道促进输精管平滑肌的浓度，这在肌肉功能障碍的治疗中有潜在的用途。
