Pannexin1 regulates α1-adrenergic receptor- mediated vasoconstriction.
Pannexin1 regulates α1-adrenergic receptor- mediated vasoconstriction.
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DOI：
10.1161/circresaha.110.237594
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发表时间：
2011-06-24
影响因子：
20.1
通讯作者：
Isakson BE
中科院分区：
文献类型：
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作者：
Billaud M;Lohman AW;Straub AC;Looft-Wilson R;Johnstone SR;Araj CA;Best AK;Chekeni FB;Ravichandran KS;Penuela S;Laird DW;Isakson BE
血管平滑肌细胞（VSMC）收缩的协调性在血压调节等血管功能中起着重要作用。然而，在阻力血管系统中负责VSMC通讯的机制尚不清楚。Pannexins（Panx）是一种嘌呤释放通道，可透过血管收缩剂ATP，因此可能在协调VSMC收缩中发挥作用。我们研究了pannexins在苯肾上腺素（PE）和KCl介导的阻力动脉收缩中的作用。免疫印迹，免疫组化和免疫金标记结合扫描和透射电子显微镜显示存在Panx 1，但不Panx 2或Panx 3在胸背阻力动脉（TDA）。在功能上，多种Panx抑制剂（甲氟喹，丙磺舒和10 Panx 1），外核苷酸酶（腺苷三磷酸双磷酸酶）和嘌呤能受体抑制剂（苏拉明和活性蓝-2）显着降低加压TDA对PE的收缩反应。用Panx 1-GFP或Panx 1 siRNA电穿孔TDA分别显示增强和减少收缩响应PE。最后，Panx抑制剂没有改变收缩反应KCl。这一结果与TDA的免疫共沉淀实验一致，TDA的免疫共沉淀实验表明Panx 1与α 1D-肾上腺素受体之间存在关联。我们的数据首次证明了Panx 1在阻力动脉中的关键作用，有助于协调VSMC收缩和可能的血压调节。
The coordination of vascular smooth muscle cell (VSMC) constriction plays an important role in vascular function such as regulation of blood pressure. However, the mechanism responsible for VSMC communication is not clear in the resistance vasculature. Pannexins (Panx) are purine releasing channels permeable to the vasoconstrictor ATP and thus may play a role in the coordination of VSMC constriction. We investigated the role of pannexins in phenylephrine (PE) and KCl mediated constriction of resistance arteries. Western blot, immunohistochemistry and immunogold labeling coupled to scanning and transmission electron microscopy revealed the presence of Panx1 but not Panx2 or Panx3 in thoracodorsal resistance arteries (TDA). Functionally, the contractile response of pressurized TDA to PE was significantly decreased by multiple Panx inhibitors (mefloquine, probenecid and 10Panx1), ectonucleotidase (apyrase) and purinergic receptor inhibitors (suramin and reactive-blue-2). Electroporation of TDA with either Panx1-GFP or Panx1 siRNA showed enhanced and decreased constriction respectively in response to PE. Lastly, the Panx inhibitors did not alter constriction in response to KCl. This result is consistent with co-immunoprecipitation experiments from TDA, which suggested an association between Panx1 and α1D-adrenoreceptor. Our data demonstrate for the first time a key role for Panx1 in resistance arteries, by contributing to the coordination of VSMC constriction and possibly regulation of blood pressure.