κ-阿片受体与β_1-肾上腺素受体交互作用抑制异丙肾上腺素诱导的心肌肥大  

Inhibition effects of U50,488H on hypertrophic myocardial cells induced by isoproterenol

作　　者：单丹[1] 王洪新[1] 苏玉虹[1] 杨育红[1] 王浩[1] 

机构地区：[1]锦州医学院分子生物学与新药开发重点实验室

出　　处：《中国临床药理学与治疗学》2005年第5期537-541,共5页Chinese Journal of Clinical Pharmacology and Therapeutics

基　　金：辽宁省教育厅高等学校重大基础研究计划项目基金(№2021720451)

摘　　要：目的:观察选择性kappa阿片受体(kappaopioidreceptor,κOR)与β肾上腺素受体(βadrenergicreceptor,βAR)在心肌细胞肥大方面的交互作用。方法:以体外培养的乳鼠心肌细胞为模型,10μmol·L-1的异丙肾上腺素(β肾上腺素受体激动剂,βAR)诱导心肌肥大,观察1μmol·L-1的U50,488H(κOR激动剂,U50)对其作用。进一步探索在100nmol·L-1ICI118,551(β2AR阻断剂)存在情况下,κOR的激活对心肌肥大的作用。用Lowry’s法测心肌细胞的蛋白质含量;用消化分离法,并利用计算机图象分析系统测心肌细胞的体积;用[3H]leucine掺入法测定心肌细胞蛋白的合成。结果:异丙肾上腺素使心肌细胞总蛋白含量、体积、蛋白合成明显增加;1μmol·L-1的U50,488H使ISO诱导的心肌细胞总蛋白含量、体积、蛋白合成减少,这种作用可被选择性κOR阻断剂norBNI(norbinaltorphimine)抑制。在ICI118,551存在的情况下,U50也能起到减弱ISO诱导心肌细胞肥大的作用。结论:U50,488H通过激活κOR与β1AR交互作用抑制ISO所诱导的心肌细胞肥大。AIM: To observe the inhibition effects of cross-talk between kappa opioid receptor (κ-OR) and β_1-adrenoceptor (β_1-AR) on hypertrophic myocardial cells induced by isoproterenol (ISO) in neonatal rats. METHODS: The total protein content was assayed by the method of Lowry's. The cardiomyocytes' volume was measured by computer photograph analysis system and the protein synthesis was assayed with [~3H] leucine intake method. RESULTS: ISO enhanced the total protein content, the cardiomyocytes' volume and the protein synthesis in myocardial cells. U50,488H (U50) showed the function inhibited by nor-BNI on reducing the previous mentioned indices induced by ISO. U50 also attenuated the hypertrophy induced by ISO combined with ICI118,551(β_2-AR inhibitor). CONCLUSION: κ-OR has a cross-talk with β_1-adrenoceptor in ISO-induced myocardial hypertrophy.

关 键 词：异丙肾上腺素 心肌肥大 U50 488H nor-BNI 

分 类 号：R966[医药卫生—药理学]