成瘾性药物对大鼠脑内G蛋白耦联受体激酶5 mRNA和蛋白水平的调控  

Regulation of G protein-coupled receptor kinase 5 mRNA and protein level in rat brain by addictive drugs

作　　者：朱敏[1] 范学良[1] 杨伟林[1] 江燕[1] 马兰[1] 

机构地区：[1]复旦大学上海医学院药理研究中心医学神经生物学国家重点实验室,上海200032

出　　处：《生理学报》2004年第5期559-565,共7页Acta Physiologica Sinica

基　　金：This work was supported by the National Natural Science Foundation of China (No.30230130) and the Ministry of Science and Technology of China (No.2003-CB515405).

摘　　要：G 蛋白耦联受体激酶 5(GRK5)在G 蛋白耦联受体信号转导中起重要调节作用。本文研究了单次给予成瘾性药物吗啡、海洛因和可卡因对大鼠脑内 GRK5 mRNA 水平的调控作用,并选取吗啡为代表,观察单次或多次给予吗啡后大鼠脑内GRK5 蛋白含量的变化。结果发现: (1)单次给予吗啡(10 mg/kg)、海洛因(1 mg/kg)或可卡因(15 mg/kg)均可引起大鼠大脑顶叶皮层、颞叶皮层和海马的GRK5 mRNA水平显著上升; (2)单次或多次给予吗啡注射可以显著上调大鼠大脑皮层GRK5 蛋白含量,而多次给予吗啡显著下调丘脑 GRK5 含量。我们的结果首次证明成瘾性药物对大脑皮层、海马等脑区的 GRK5 在mRNA 水平和蛋白水平都有调控作用,提示 GRK5 可能在精神活性物质的成瘾中起作用。G protein-coupled receptor kinase 5 (GRK5) plays an important role in the regulation of GPCR-transduced signals. Our previous study showed that acute administration of morphine could significantly increase GRK5 mRNA level in the cerebral cortex and hippocampus of the rat brain. The current study investigated the potential effects of acute administration of addictive drugs including morphine, heroine and cocaine on GRK5 mRNA level in the rat brain using in situ hybridization and analyzed the effects of acute and chronic morphine treatments on GRK5 protein level in the rat brain using Western blotting assay. Our results showed that 2 h after the initial morphine (10 mg/ kg), cocaine (15 mg/kg) and heroine (1 mg/kg) treatment, the mRNAlevel of GRK5 in the parietal cortex increased about 110% (P<0.01), 70% (P<0.05) and 100% (P<0.01), respectively. In the temporal cortex, GRK5 mRNA level increased about 90% (P<0.01), 40% (P<0.05) and 80.0% (P<0.01), respectively . In the hippocampus, the mRNA level of GRK5 increased about 60% (P<0.01), 30% (P<0.05) and 80% (P<0.01). However, the mRNA level of GRK5 remained unchanged after acute morphine, cocaine or heroine treatment. In the cerebral cortex of the rat brain, the acute administration of morphine (NS-Mor) increased GRK5 protein level by about 60% while the chronic morphine treatment (Mor-Mor) increased GRK5 protein level even higher [about 130% compared with the control group (chronic saline treatment, NS-NS) group, P<0.01]. In the hippocampus, GRK5 protein level remained unchanged after acute administration of morphine (P>0.1), while the level of GRK5 protein tended to decrease after chronic morphine treatment (P=0.098). In the thalamus, acute morphine treatment caused no change in GRK5 protein level (P>0.1) while after chronic morphine treatment, GRK5 protein level decreased significantly (more than 90%, P<0.01), Taken together, our results indicate that addictive drugs can regulate GRK5 in the rat brain on protein level as well as on mRNA level and sugg

关 键 词：吗啡 海洛因 可卡因 G蛋白耦联受体激酶 成瘾 

分 类 号：R96[医药卫生—药理学]