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.pdfVIP

生理学报 Acta Physiologica Sinica , October 25, 2004, 56 (5): 559-565 559 研究论文 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 朱 敏, 范学良, 杨伟林, 江 燕, 马 兰* 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 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。 关键词: 吗啡; 海洛因; 可卡因; G 蛋白耦联受体激酶; 成瘾 中图分类号: Q426; R96 Regulation of G protein-coupled receptor kinase 5 mRNA and protein level in rat brain by addictive drugs ZHU Min, FAN Xue-Liang, YANG Wei-Lin, JIANG Yan, MA Lan* Pharmacological Research Center, Shanghai Medical College, Fudan University, State Key Lab of Medical Neurobiology, Fudan University, Shanghai 200032, China Abstract: 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 mRNA level of GRK5 in the parietal cortex increased about 110% (P0.01), 70% (P0.05) and 100% (P0.01), respectively. In the temporal cortex, GRK5 mRNA level increased about 90% (P0.01), 40% (P0.05) and 80.0% (P0.01), respective