血管加压素1a与血管加压素2受体在精氨加压素调节缺氧血管平滑肌细胞蛋白激酶C表达中的作用  

Vasopressin-1a and vasopressin-2 receptors in argipressin regulating expression of protein kinase C of vascular smooth muscle cell after hypoxia

作　　者：杨光明[1] 徐竞[1] 李涛[1] 明佳[1] 陈玮[1] 刘良明[1] 

机构地区：[1]第三军医大学大坪医院野战外科研究所第二研究室,创伤烧伤与复合伤国家重点实验室,重庆400042

出　　处：《中国药理学与毒理学杂志》2009年第1期29-33,共5页Chinese Journal of Pharmacology and Toxicology

基　　金：国家杰出青年科学基金资助项目(30625037);国家重点基础发展计划(973)资助项目(2005CB522601);教育部创新团队资助计划(IRT0712)~~

摘　　要：目的观察血管加压素1a(V1a)受体与V2受体拮抗剂对精氨加压素(AVP)调节缺氧血管平滑肌细胞(VSMC)蛋白激酶C(PKC)α,δ和ε亚型表达的影响,以及磷脂酶C(PLC)、磷脂酶D(PLD)和磷脂酶A2(PLA2)活性的变化。方法缺氧培养大鼠肠系膜上动脉VSMC,采用Western蛋白印迹法检测PKCα,δ和ε亚型蛋白表达;采用酶偶联荧光分析法测定PLC和PLD的活性,酸碱滴定法检测PLA2的活性。结果缺氧处理1.5h,VSMC胞膜PKC-α和ε亚型蛋白表达量明显升高,AVP进一步升高胞膜PKC-α和ε的表达。V1a受体拮抗剂d(CH2)5[Tyr2(Me)]AVP预处理可明显拮抗AVP诱导的胞膜PKCα和ε亚型蛋白表达升高,同时也明显拮抗AVP诱导的缺氧VSMC中PLC和PLD活性升高。而V2受体拮抗剂d(CH2)[d-Ile2Abu4]AVP对缺氧诱导的胞膜PKC-α和ε表达增加和VSMC中PLC和PLD活性升高无明显作用。结论AVP诱导PKC激活的机制可能与V1a受体介导的PLC/PLD途径有关,而V2受体在这一信号传导途径中可能并不起主要作用。AIM To investigate the effects of vasopressin-1α （V1α） receptor and V2 receptor antagonists on argipressin （ AVP ） regulating the expression of protein kinase C （PKC）-α, and e isoforms of vascular smooth muscle cell （VSMC） and the changes in phospholipases C （PLC）, D （PLD） and A2 （ PLA2 ） activity. METHODS VSMCs from superior mesenteric artery of rats were hypoxia-treated for 1.5 h. The expression of PKC-α, 8 and e isoforms was detected with Western blot. The PLC and PLD activities were assayed by enzyme-coupled fluorimetric analysis, and PLA2 activity was assayed by acid-base titration. RESULTS After hypoxia, the expression of VSMC particulate PKC-α and e increased, and AVP treatment further increased expression of PKC-α and e in the particulate fractions. V1α Receptor inhibitor d（ CH2 ） 5 [ TYr2 （ Me ） ] AVP significantly antag-onized this effect of AVP, simultaneously, also antagonized AVP-induced increase in PLC and PLD activities of VSMC after hypoxia. But V2 receptor antagonist d （ CH2 ） [ d-Ile2Abu4 ] AVP had no significant influence on AVP-induced increase in expression of PKC-α and ε isoforms and the activities of PLC and PLD. CONCLUSION AVP induces translocation/ activation of PKC isoforms in VSMC mainly through a V1α receptor-dependent PLC/PLD mechanism, while V2 receptor plays a lesser role in the signal transduction pathway.

关 键 词：受体 血管加压素 血管平滑肌细胞 缺氧 精氨 加压素 蛋白激酶C 磷脂酶C 磷脂酶D 磷脂酶A2 

分 类 号：R96[医药卫生—药理学]