[1]赵林波,隋念含,蒙国懿,等.RGS4过表达对甲基苯丙胺依赖大鼠纹状体mGluR5信号传导通路相关蛋白表达的影响[J].中国药理学通报,2019,(08):1115-1120.[doi:10.3969/j.issn.1001-1978.2019.08.016]
 ZHAO Lin-bo,SUI Nian-han,et al.Effect of RGS4 overexpression on related protein expression of mGluR5-mediated signaling pathway in methamphetamine-dependent rat striatum[J].Chinese Pharmacological Bulletin,2019,(08):1115-1120.[doi:10.3969/j.issn.1001-1978.2019.08.016]
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RGS4过表达对甲基苯丙胺依赖大鼠纹状体mGluR5信号传导通路相关蛋白表达的影响()
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《中国药理学通报》[ISSN:/CN:]

卷:
期数:
2019年08期
页码:
1115-1120
栏目:
论著
出版日期:
2019-08-14

文章信息/Info

Title:
Effect of RGS4 overexpression on related protein expression of mGluR5-mediated signaling pathway in methamphetamine-dependent rat striatum
文章编号:
1001-1978(2019)08-1115-06
作者:
赵林波12隋念含2蒙国懿2洪仕君3李利华3邢豫明4赵永娜2
1.云南中医药大学信息学院,云南 昆明 650500; 2.昆明医科大学药学院暨云南省天然药物药理重点实验室,云南 昆明 650500; 3.昆明医科大学法医学院,云南 昆明 650500; 4.云南省公安厅禁毒处毒品分析与禁毒技术公安部重点实验室,云南 昆明 650228
Author(s):
ZHAO Lin-bo1 2 SUI Nian-han2 MENG Guo-yi2 HONG Shi-jun3 LI Li-hua3 XING Yu-ming4 ZHAO Yong-na2
1.School of Institute of Information, Yunnan University of Chinese Medicine, Kunming 650500, China; 2.School of Pharmaceutical Sciences and Yunnan Key Lab of Pharmacology for Natural Product, Kunming Medical University, Kunming 650500, China; 3.School of Forensic Medicine, Kunming Medical University, Kunming 650500, China; 4.Key Lab of drug analysis and drug control technology of Yunnan Provincial Police Department, Kunming 650228, China
关键词:
甲基苯丙胺 纹状体 条件位置偏爱 G蛋白信号调节因子4 代谢型谷氨酸受体5 G蛋白α亚单位蛋白q 磷脂酶C-β1
Keywords:
methamphetamine striatum CPP RGS4 mGluR5 Gαq PLCβ1
分类号:
R-332; R322.81; R373.1; R392.11; R971.7; R971.93; R977.6
DOI:
10.3969/j.issn.1001-1978.2019.08.016
文献标志码:
A
摘要:
目的 通过建立大鼠甲基苯丙胺(METH)依赖条件位置偏爱模型(CPP),研究脑纹状体内G蛋白信号调节因子4(RGS4)过表达引起的代谢型谷氨酸受体5(mGluR5)信号传导通路相关蛋白表达变化,以及对大鼠CPP行为的影响。方法 将大鼠随机分为正常组、生理盐水(NS)组、METH组、Ad5-RGS4-EGFP组、Ad5-EGFP组。正常组不做处理,其余各组脑纹状体分别立体定位注射磷酸盐缓冲液(PBS)、PBS、过表达腺病毒载体Ad5-RGS4-EGFP和阴性对照腺病毒载体Ad5-EGFP,分析各组大鼠CPP行为,Western blot检测脑纹状体内RGS4、mGluR5、Gαq、PLCβ1等蛋白的表达。结果 Ad5-RGS4-EGFP组CPP差值低于METH组和Ad5-EGFP组(P<0.05),高于NS组(P<0.05)。Ad5-RGS4-EGFP组RGS4蛋白表达均不同程度高于其余4组(P<0.05,P<0.01),mGluR5、Gαq表达低于METH组和Ad5-EGFP组(P<0.05),略高于正常组和NS组(P>0.05), PLCβ1表达略有变化,但差异无显著性。结论 纹状体内RGS4过表达可明显缓解METH成瘾性大鼠CPP行为,机制可能与RGS4过表达后,负性调控mGluR5介导的Gαq及PLCβ1信号传导通路相关。
Abstract:
Aim To investigate the effect of the regulator of G-protein signaling 4(RGS4)overexpression in rat striatum on the related protein expression of metabolic glutamate receptor 5(mGluR5)signaling pathway and the conditioned place preference(CPP)behavior in rats, by establishing the METH-dependent CPP model.Methods Rats were divided into five groups: normal, normal saline(NS), METH, Ad5-RGS4-EGFP and Ad5-EGFP group.Normal group was without any administration, while the striatum of the other groups were respectively stereotactic injected with phosphate buffer methamphetamine(METH)-depardent soline(PBS), PBS, overexpressed adenovirus vector Ad5-RGS4-EGFP and negative control adenovirus vector Ad5-EGFP.The CPP behavior of rats in each group was analyzed.The expression of RGS4, mGluR5, Gαq, PLC1 was measured in rat striatum tissue by Western blot.Results The difference of CPP in Ad5-RGS4-EGFP group decreased compared with that in METH group and Ad5-EGFP group(P<0.05), and increased compared with that in NS group(P<0.05).RGS4 expression in Ad5-RGS4-EGFP group increased compared with that in other groups(P<0.05,P<0.01), the expression levels of mGluR5, Gαq decreased compared with those in METH group and Ad5-EGFP group(P<0.05), while slightly increased compared with that in normal group and NS group(P>0.05).PLCβ1 expression changed with no significant difference.Conclusions RGS4 overexpression in striatum is able to alleviate the CPP behavior in METH-dependent rats, and its mechanism may be associated with the overexpression of RGS4 in METH-dependent rat striatum, which could down-regulate the mGluR5-mediated Gαq and PLCβ1 signaling pathway.

参考文献/References:

[1] 刘 溪, 代振凤, 蒲小平.甲基苯丙胺成瘾机制进展[J].中国新药杂志,2017, 26(21):2541-5.
[1] Liu X, Dai Z F, Pu X P.Advances in the mechanism of methamphetamine addiction[J].Chin J New Drugs,2017,26(21):2541-5.
[2] 杨黎华, 白 洁.单胺类神经递质在药物成瘾中的作用机制[J].中国药理学通报,2015,31(2):149-51.
[2] Yang L H, Bai J.Roles of monoamine neurotransmitters in the drug addiction[J].Chin Pharmacol Bull, 2015,31(2):149-51.
[3] 黄书才, 朱早晨,杨 铖,等.药物成瘾行为相关学习记忆的研究现状[J].中国药物依赖性杂志, 2017,26(4):293-9.
[3] Huang S C, Zhu Z C, Yang C, et al.The research status of learning and memory related to drug addiction behavior[J].Chin J Drug Depend, 2017,26(4):293-9
[4] Schwendt M, McGinty J F.Regulator of G-protein signaling 4 interacts with metabotropic glutamate receptor subtype 5 in rat striatum: relevance to amphetamine behavioral sensitization[J].J Pharmacol Exp Ther,2007,323(2):650-7.
[5] Rorabaugh B R, Rose M J, Stoops T S, et al.Regulators of G-protein signaling 2 and 4 differentially regulate cocaine-induced rewarding effects[J].Physiol Behav,2018,195: 9-19.
[6] Li S J, Li Y, Cui S C, et al.Splicing factor transformer-2β(Tra2β)regulates the expression of regulator of G protein-signaling 4(RGS4)gene and is induced by morphine[J].PLoS One,2013,8(8):e72220.
[7] Traynor J.Regulator of G protein-signaling proteins and addictive drugs[J].Ann N Y Acad Sci,2010, 1187:341-52.
[8] Paxinos G, Watson C.大鼠脑立体定位图谱, 第三版[M].北京:人民卫生出版社,2005:图16.
[8] Paxinos G, Watson C.The rat brain in stereotaxic coordinates, 3rd edition[M].Beijing: People's Medical Publishing House,2005:16
[9] Niwa M, Nitta A, Mizoguchi H,et al.A novel molecule “shati” is involved in methamphetamine-induced hyperlocomotion, sensitization, and conditioned place preference[J].J Neurosci,2007,27(28): 7604-15.
[10] Zhang Y, Gao Y, Speth R C,et al.Adenoviral and adeno-associated viral vectors-mediated neuronal gene transfer to cardiovascular control regions of the rat brain[J].Int J Med Sci,2013,10(5):607 -16.
[11] 何以丰, 喻 红, 吴昊泉,等.GFP标记的GDNF重组腺病毒载体的构建和体内外表达[J].复旦学报(自然科学版),2003,42(4):519-52.
[11] He Y F, Y H, Wu H Q, et al.Construction of a GFP-labeled recombinant adenovirus harbouring GDNF and its expression in rat neural cells in vitro and in vivo[J].J Fudan Univ(Nat Sci), 2003, 42(4): 519-52.
[12] 朱 晨,刘 伟,李 璟,等.酪氨酸羟化酶与钩藤碱抑制甲基苯丙胺依赖小鼠条件性位置偏爱的关系研究[J].中国药理学通报, 2018,34(9):1226-30.
[12] Zhu C, Liu W, Li J, et al.Effect of rhynchophylline on expression of TH in methamphetamine-induced CPP mice[J].Chin Pharmacol Bull, 2018, 34(9):1226-30.
[13] Kim J, Lee S, Kang S, et al.Regulator of G-protein signaling 4(RGS4)controls morphine reward by glutamate receptor activation in the nucleus accumbens of mouse brain[J].Mol Cells, 2018,41(5):454-64.
[14] 赵林波,隋念含,李利华,等.甲基苯丙胺依赖对大鼠纹状体RGS4和mGluR5受体信号传导的影响[J].中国临床药理学与治疗学,2018,23(5):536-40.
[14] Zhao L B, Sui N H, Li L H, et al.Methamphetamine dependent influenced RGS4 and mGluR5 receptor signaling in striatum of rats[J].Chin J Chin Pharmacol Ther, 2018, 23(05):536-40.
[15] Mao L M, Wang Q.Phosphorylation of group I metabotropic glutamate receptors in drug addiction and translational research[J].J Transl Neurosci(Beijing), 2016,1(1):17-23.
[16] Schwendt M, Sigmon S A, McGinty J F.RGS4 overexpression in the rat dorsal striatum modulates mGluR5-and amphetamine-mediated behavior and signaling[J].Psychopharmacology(Berl),2012,221(4): 621-35.
[17] Mathews J L, Smrcka A V, Bidlack J M.A novel G Gβγ-subunit inhibitor selectively modulates mu-opioid-dependent antinociception and attenuates acute morphine-induced antinociceptive tolerance and dependence[J].J Neurosci,2008, 28(47):12183-9.
[18] Lyon A M, Tesmer V M, Dhamsania V D, et al.An autoinhibitory helix in the C-terminal region of phospholipase C-β mediates Gαq activation[J].Nat Struct Mol Biol, 2011,18(9):999-1005.
[19] Cui G, Bernier B E, Harnett M T, et al.Differential regulation of action potential-and metabotropic glutamate receptor-induced Ca2+ signals by inositol 1,4,5-trisphosphate in dopaminergic neurons[J].J Neurosci,2007,27(17):4776-85.
[20] Hepler J R, Berman D M, Gilman A G, et al.RGS4 and GAIP are GTPase-activating proteins for Gq alpha and block activation of phospholipase C beta by gamma-thio-GTP-Gq alpha[J].Proc Natl Acad Sci USA, 1997,94(2):428-32.

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备注/Memo

备注/Memo:
收稿日期:2019-02-27,修回日期:2019-04-19
基金项目:云南省应用基础研究计划联合专项基金资助项目(No 2012FB023)
作者简介:赵林波(1988-),女,硕士,讲师,研究方向:神经药理学,E-mail:82925224@qq.com;
赵永娜(1968-),女,博士,教授,研究方向:神经药理学,通讯作者,E-mail:mszhaoyn@163.com
更新日期/Last Update: 2019-08-14