δ阿片受体激活诱导心肌细胞增殖的信号转导途径  

Signal transduction of δ-opioid receptor stimulation on proliferation of cultured myocardial cells

作　　者：赵敏[1] 王洪新[1] 崔蕾[1] 

机构地区：[1]辽宁医学院药理学教研室,辽宁锦州121001

出　　处：《中国药理学与毒理学杂志》2007年第5期377-380,共4页Chinese Journal of Pharmacology and Toxicology

基　　金：辽宁省自然科学基金(20042170)~~

摘　　要：目的研究δ阿片受体激活剂D-丙(2)-D-亮(5)脑啡肽(DADLE)诱导心肌细胞增殖的可能信号途径。方法体外培养乳大鼠心肌细胞,采用结晶紫法和[3H]TdR检测心肌细胞的增殖;Western印迹法测心肌细胞外信号调节激酶(ERK)磷酸化水平。结果DADLE1μmol.L-1增强心肌细胞ERK磷酸化,促进心肌细胞增殖,δ阿片受体抑制剂纳曲吲哚10μmol.L-1,蛋白激酶C(PKC)特异性抑制剂星形孢菌素1μmol.L-1和ERK特异性抑制剂U012610nmo.lL-1明显降低ERK磷酸化水平,抑制DADLE的促心肌细胞增殖作用。结论DADLE可能通过δ阿片受体活化PKC,进而激活有丝分裂原激活蛋白激酶ERK通路诱导心肌细胞增殖。AIM To study signal transduction in cultured myocardial proliferation induced by [ D-Ala2, D-Leu5 ]-enkephalin （ DADLE ）, a 8-opioid receptor agonist. METHODS Myocardial cells of neonatal rats were cultured in vitro. The cellular proliferation was determined by crystal violet uptake and [ 3H ] TdR thymidine incorporation. The degree of extracellular signal-regulated kinase （ERK） phosphorylation was determined by Western blot. RESULTS DADLE （ 1μmol·L^-1） promoted the myocardial cells proliferation. Nahrindole （10μmol·L^-1） , a selective 8-opioid receptor antagonist, staurosporine （ 1μmol·L^-1） , a selective protein kinase C （ PKC ） antagonist, and U0126 （10 nmol-L-l）, a selective ERK antagonist, obviously inhibited the degree of ERK phospho- rylation and the myocardial proliferation induced by DADLE. CONCLUSION DADLE may promote myocardial proliferation through activating PKC by 8-opioid receptor and then activating the MAPK-ERK pathway.

关 键 词：受体 阿片样 δ 心肌 细胞 培养的 细胞增殖 细胞外信号调节激酶 

分 类 号：R96[医药卫生—药理学]