慢性缺氧时心脏κ-阿片受体对β-受体信号的调节作用  

MODULATION OF β-ADRENERGIC SIGNALING BY κ-OPIOID RECEPTOR IN THE HEART FOLLOWING CHRONIC HYPOXIA

作　　者：裴建明[1] 毕辉[1] 王跃民[1] 马恒[1] 朱妙章[1] 

机构地区：[1]第四军医大学生理学教研室

出　　处：《解放军医学杂志》2003年第4期321-323,共3页Medical Journal of Chinese People's Liberation Army

基　　金：全军医学科研"十五"计划面上项目 (编号 0 1MB1 2 9);第四军医大学创新工程重点项目 (编号CX0 1F0 0 1 )资助课题

摘　　要：为研究慢性缺氧时κ 阿片受体对β 受体信号的调节作用及机制 ,用光谱荧光法测定电刺激引起的细胞内 [Ca2 + ]i瞬变 ,用RT PCR测定κ 阿片受体mRNA的表达 ,用Westernblot观察缺氧后G蛋白的变化。结果显示 ,κ 阿片受体选择性激动剂U5 0 4 88H可明显抑制β 受体激动剂异丙肾上腺素增加 [Ca2 + ]i瞬变幅度的作用 ,慢性缺氧后 ,该作用明显减弱 ;κ 阿片受体mRNA的表达和Gi蛋白的活性在慢性缺氧后无明显改变 ,而小Gs蛋白的活性明显降低。提示κ 阿片受体对β 受体信号的负性调节作用在慢性缺氧后显著减弱。其机制可能部分与介导βTo determine the regulatory effect of κ opioid receptor stimulation on β adrenoceptor signaling and its underlying mechanism, single ventricular myocytes were isolated from the heart of rat subjected to chronic hypoxia for 4 weeks. The electrically induced [Ca 2+ ] i transient were measured using a spectrofluorometric method. RT PCR was used to determine the mRNA of κ opioid receptor, and Western blot was used to determine the Gi and Gs protein. β adrenoceptor stimulation with isoproterenol increased the amplitude of the electrically induced [Ca 2+ ] i transient in myocytes of normoxic rats. U50488H, a selective κ opioid receptor agonist, significantly inhibited the effect of isoproterenol. In the heart of chronically hypoxic rats, the inhibition of U50488H was blunted. RT PCR revealed no significant change in mRNA of κ opioid receptor. Western blot showed no change in Gi protein. While biologically active Gs small protein decreased significantly. The results indicate that the negative modulation of κ opioid receptor on β adrenoceptor is attenuated in the heart of chronically hypoxic rat. The decrease in Gs protein may be partially responsible for the attenuation.

关 键 词：慢性缺氧 心脏 κ—阿片受体 β受体信号 调节作用 

分 类 号：R364.4[医药卫生—病理学]