Modulation of CaV1.2 calcium channel by neuropeptide W regulates vascular myogenic tone via G protein-coupled receptor 7
Modulation of CaV1.2 calcium channel by neuropeptide W regulates vascular myogenic tone via G protein-coupled receptor 7
复制标题
神经肽 W 对 CaV1.2 钙通道的调节通过 G 蛋白偶联受体 7 调节血管肌原张力。
DOI：
10.1097/hjh.0000000000000723
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发表时间：
2015-12-01
影响因子：
4.9
通讯作者：
Wang, Juejin
中科院分区：
文献类型：
--
作者：
Ji, Li;Zhu, Huayuan;Wang, Juejin
目的：神经肽W（NPW）是G蛋白偶联受体7（GPR 7）的内源性配体，最早被发现在中枢神经系统中发挥重要作用。在外周，NPW也存在，并通过L型钙通道调节细胞内钙稳态。本研究旨在探讨NPW-GPR 7对血管平滑肌细胞Ca（V）1.2钙通道功能的影响及对动脉血管紧张素Ⅱ的影响。方法：采用全细胞膜片钳技术，观察NPW-23对异源转染的人胚肾293细胞和大鼠血管平滑肌细胞Ca（V）1.2钙通道的影响。应用活体系统研究NPW-23在动脉肌源性张力中的生理功能。结果：NPW受体GPR 7与Ca（V）1.2通道在动脉平滑肌中共表达。NPW-23可通过GPR 7增加转染人胚肾293细胞和VSMCs的I-Ca、I-L，但这种作用可被磷脂酶C（PLC）和蛋白激酶C（PKC）抑制剂所阻断，而不能被蛋白激酶A或蛋白激酶G抑制剂所阻断。应用NPW-23后，pan phospho-PKC的表达增加，并且，细胞内由PLC催化的第二信使甘油二酯水平增加1.5-2倍。应用NPW-23可增加大鼠肠系膜动脉的压力诱导血管张力。结论：NPW-23通过PLC/PKC信号通路介导的GPR 7调节I-Ca、I-L，调节血管肌源性张力，可能参与血管性高血压的发生发展。
Objective: Neuropeptide W (NPW), an endogenous ligand for the G protein-coupled receptor 7 (GPR7), was first found to make important roles in central nerve system. In periphery, NPW was also present and regulated intracellular calcium homeostasis by L-type calcium channels. This study was designed to discover the effects of NPW-GPR7 on the function of Ca(V)1.2 calcium channels in the vascular smooth muscle cells (VSMCs) and vasotone of arterial vessels.Methods: By whole-cell patch clamp, we studied the effects of NPW-23, the active form of NPW, on the Ca(V)1.2 channels in the heterologously transfected human embryonic kidney 293 cells and VSMCs isolated from rat. Living system was used to explore the physiological function of NPW-23 in arterial myogenic tone. To investigate the pathological relevance, NPW mRNA level of mesenteric arteries was measured in the hypertensive and normotensive rats.Results: NPW's receptor GPR7 was coexpressed with Ca(V)1.2 channels in arterial smooth muscle. NPW-23 increased the I-Ca,I-L in transfected human embryonic kidney 293 cells and VSMCs via GPR7, which could be abrogated by phospholipase C (PLC)/protein kinase C (PKC) inhibitors, not protein kinase A or protein kinase G inhibitor. After NPW-23 application, the expression of pan phospho-PKC was increased; moreover, intracellular diacylglycerol level, the second messenger catalyzed by PLC, was increased 1.5-2-fold. Application with NPW-23 increased pressure-induced vasotone of the rat mesenteric arteries. Importantly, the expression of NPW was decreased in the hypertensive rats.Conclusion:NPW-23 regulates I-Ca,I-L via GPR7, which is mediated by PLC/PKC signaling, and such a mechanism plays a role in modulating vascular myogenic tone, which may involve in the development of vascular hypertension.