title: Modulation of CaV1.2 calcium channel by neuropeptide W regulates vascular myogenic tone via G protein-coupled receptor 7.
abstract: 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 CaV1.2 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 CaV1.2 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 CaV1.2 channels in arterial smooth muscle. NPW-23 increased the ICa,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.
  
  
  CONCLUSIONS
  NPW-23 regulates ICa,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.
authors.affiliation: aKey Laboratory of Cardiovascular Disease and Molecular Intervention, Department of Physiology, Nanjing Medical University bDepartment of Hematology, the First Affiliated Hospital of Nanjing Medical University, Nanjing, China. *Li Ji and Huayuan Zhu contributed equally to the writing of this article.
authors.forename: Li
authors.initials: L
authors.lastname: Ji
authors.forename: Huayuan
authors.initials: H
authors.lastname: Zhu
authors.forename: Hong
authors.initials: H
authors.lastname: Chen
authors.forename: Wenyong
authors.initials: W
authors.lastname: Fan
authors.forename: Junjie
authors.initials: J
authors.lastname: Chen
authors.forename: Jing
authors.initials: J
authors.lastname: Chen
authors.forename: Guoqing
authors.initials: G
authors.lastname: Zhu
authors.forename: Juejin
authors.initials: J
authors.lastname: Wang
mesh_terms: D000818:Animals; D001794:Blood Pressure; D020746:Calcium Channels, L-Type / Q000235:genetics / Q000378:metabolism*; D004075:Diglycerides / Q000378:metabolism; D057809:HEK293 Cells; D006801:Humans; D006973:Hypertension / Q000378:metabolism; D008297:Male; D008638:Mesenteric Arteries / Q000502:physiology; D009131:Muscle, Smooth, Vascular / Q000187:drug effects / Q000378:metabolism / Q000503:physiopathology*; D032389:Myocytes, Smooth Muscle / Q000378:metabolism; D009479:Neuropeptides / Q000235:genetics / Q000378:metabolism*; D047428:Protein Kinase Inhibitors / Q000494:pharmacology; D012333:RNA, Messenger / Q000378:metabolism; D051381:Rats; D043562:Receptors, G-Protein-Coupled / Q000235:genetics / Q000378:metabolism*; D018013:Receptors, Neuropeptide / Q000235:genetics / Q000378:metabolism*; D015398:Signal Transduction
chemical_list: D020746:Calcium Channels, L-Type; D004075:Diglycerides; C419385:L-type calcium channel alpha(1C); C485722:NPBWR1 protein, human; C467731:NPW protein, human; D009479:Neuropeptides; D047428:Protein Kinase Inhibitors; D012333:RNA, Messenger; D043562:Receptors, G-Protein-Coupled; D018013:Receptors, Neuropeptide