神经药理学报 ›› 2017, Vol. 7 ›› Issue (1): 53-64.DOI: 10.3969/j.issn.2095-1396.2017.01.007
• 综述 • 上一篇
孙志华，罗素兰
出版日期:2017-02-26
发布日期:2017-12-01
通讯作者:
罗素兰，女，海南大学长江学者特聘教授，博士，博士生导师；研究方向：海洋药物与生物技术；Tel：+86-089866289538，E-mail：luosulan2003@163.com
作者简介:孙志华，男，博士研究生；研究方向：芋螺毒素抗癌研究；E-mail：zhihuasun918@163.com
基金资助:国家自然科学基金项目（No.81420108028），长江学者和创新团队发展计划（No.IRT_15R15），海南省普通高等学校研究生创新科研课题（No.Hyb2016-08）
SUN Zhi-hua，LUO Su-lan
Online:2017-02-26
Published:2017-12-01
Contact:
罗素兰，女，海南大学长江学者特聘教授，博士，博士生导师；研究方向：海洋药物与生物技术；Tel：+86-089866289538，E-mail：luosulan2003@163.com
About author:孙志华，男，博士研究生；研究方向：芋螺毒素抗癌研究；E-mail：zhihuasun918@163.com
Supported by:国家自然科学基金项目（No.81420108028），长江学者和创新团队发展计划（No.IRT_15R15），海南省普通高等学校研究生创新科研课题（No.Hyb2016-08）
摘要： 烟碱型乙酰胆碱受体（nicotinic acetylcholine receptors，nAChRs）属于配体门控离子通道，广泛分布于中枢神经系统、周围神经系统和肌肉组织非神经系统中，不同的亚基组成形式决定了其对激动剂或拮抗剂不同的亲和力。近期的研究表明，nAChRs 与神经痛、帕金森病、阿尔茨海默病（老年痴呆症）以及小细胞肺癌、乳腺癌、宫颈癌等多种疾病的病理进程息息相关。该文就几种疾病与nAChRs 结构、功能及其二者相关性进行综述，并重点阐述 nAChRs 介导的 α- 芋螺毒素抗肿瘤研究进展，以期为芋螺毒素的抗肿瘤药物的研发提供理论依据。
中图分类号:
孙志华, 罗素兰. 烟碱型乙酰胆碱受体及其相关疾病[J]. 神经药理学报, 2017, 7(1): 53-64.
SUN Zhi-hua, LUO Su-lan. Nicotinic Acetylcholine Receptors and Diseases[J]. ACTA NEUROPHARMACOLOGICA, 2017, 7(1): 53-64.
| [1] Edson X Albuquerque, Sdna F R Pereira, Manickavasagom Alkondon, et al. Mammalian nicotinic acetylcholine receptors: from structure to function[J]. Physiological Reviews, 2009, 89(1): 73-120.[2] Dang Ning-ning, Meng Xian-guang, Song Hai-yan. Nicotinic acetylcholine receptors and cancer[J]. Biomedical Reports, 2016, 4(5): 515-518.[3] Sergei Grando. Connections of nicotine to cancer[J]. Nature Reviews Cancer, 2014, 14(6): 419-429.[4] Bianca M Conti-Tronconi, Kathryn E Mclane, Michael A Raftery, et al. The nicotinic acetylcholine receptor: structure and autoimmune pathology[J]. Critical Reviews in Biochemistry & Molecular Biology, 1994, 29(2): 69-123.[5] Volodymyr Gerzanich, Wang Fan, Alexander Kuryatov, et al. α5 Subunit alters desensitization, pharmacology, ca++ permeability and ca++ modulation of human neuronal α3 nicotinic receptors[J].J Pharmacology Experimental Therapeutics, 1998, 286(1): 311-320.[6] Eline K M Lebbe, Steve Peigneur, Isuru Wijesekara, et al. Conotoxins targeting nicotinic acetylcholine receptors: an overview[J]. Marine Drugs, 2014, 12(5): 2970-3004.[7] Cecilia Gotti, Francesco Clementi, Alice Fornari, et al. Structural and functional diversity of native brain neuronal nicotinic receptors[J]. Biochemical Pharmacology, 2009, 78(7): 703-711.[8] Jon Lindstrom, Paul Whiting, Ralf Schoepfer, et al. Structure of neuronal nicotinic receptors[J]. Springer Berlin Heidelberg, 1988, doi: 10.1007/978-3-642-74167-8_13.[9] Raymond Hurst, Hans Rollema, Daniel Bertrand. Nicotinic acetylcholine receptors: from basic science to therapeutics[J]. Pharmacology & Therapeutics, 2013, 137(1): 22-54.[10] Su-lan Luo, Dongting Zhangsun, Wu Yong, et al. Characterization of a novel alpha-conotoxin from conus textile that selectively targets alpha6/alpha3beta2betab3 nicotinic acetylcholine receptors[J]. J Medicinal Chemistry, 2012, 56(23): 9655-9663.[11] Luo Su-lan, Dongting Zhang-sun, Christina I Schroeder, et al. A novel α4/7-conotoxin LvIA from Conus lividus that selectively blocks α3β2 vs. α6/α3β2β3 nicotinic acetylcholine receptors[J]. Faseb J: official Publication of the Federation of American Societies for Experimental Biology, 2014, 28(4): 1842-1853.[12] Annette Nicke, Susan Wonnacott, Richard J Lewis. Alpha-conotoxins as tools for the elucidation of structure and function of neuronal nicotinic acetylcholine receptor subtypes[J]. J European Biochemistry, 2004, 271(12): 2305–2319.[13] Katju Brejc, Willem J van Dijk, Remco V Klaassen, et al. Crystal structure of an ACh-binding protein reveals the ligand-binding domain of nicotinic receptors[J]. Nature, 2001, 411(6835): 269-276.[14] Bo Lin, Xu Man-yu, Zhu Xiao-peng, et al. From crystal structure of α-conotoxin GIC in complex with Ac-AChBP to molecular determinants of its high selectivity for α3β2 nAChR[J]. Scientific Reports, 2016, 6: 22349.[15] Patrick H N Celie, Igor E Kasheverov, Dmitry Y Mordvintsev, et al. Crystal structure of nicotinic acetylcholine receptor homolog AChBP in complex with an alpha-conotoxin PnIA variant[J]. Nature Structural & Molecular Biology, 2005, 12(7): 582-588.[16] Chris Ulens, Ronald C Hogg, Patrick H Celie, et al. Structural determinants of selective α-conotoxin binding to a nicotinic acetylcholine receptor homolog AChBP[J]. Proceedings of the National Academy of Sciences USA, 2006, 103(10): 3615-3620.[17] Sebastien Dutertre, Chris Ulens, Regina Buttner, et al. AChBP-targeted alpha-conotoxin correlates distinct binding orientations with nAChR subtype selectivity[J]. Embo J, 2007, 26(16): 3858-3867.[18] Marios Zouridakis, Petros Giastas, Eleftherios Zarkadas, et al. Crystal structures of free and antagonist-bound states of human α9 nicotinic receptor extracellular domain[J]. Nature Structural & Molecular Biology, 2014, 21(11): 976-980.[19] Claudio L Morales-Perez, Colleen M Noviello, Ryan E Hibbs. X-ray structure of the human α4β2 nicotinic receptor[J]. Nature, 2016, 538(7625): 411.[20] Patrizia Russo, Alessio Cardinale, Stefano Margaritora, et al. Nicotinic receptor and tobacco-related cancer[J]. Life Sciences, 2012, 91(21–22): 1087-1092.[21] Sergio Fucile. Ca2+ permeability of nicotinic acetylcholine receptors[J]. Cell Calcium, 2004, 35(1): 1-8.[22] Laura Jean Bierut. Nicotine dependence and genetic variation in the nicotinic receptors[J]. Drug & Alcohol Dependence, 2009, 104(supplement 1): S64-S69.[23] F Fasoli, Gotti C. Structure of neuronal nicotinic receptors[M/CD]. Springer International Publishing, 2015, 23:1-17.与8重复[24] 蔡建光, 印大中. 阿尔茨海默病主要相关基因及其功能蛋白研究进展[J]. 中国神经免疫学和神经病学杂志, 2006, 13(2): 120-123.[25] John Hardy, Dennis J Selkoe. The amyloid hypothesis of Alzheimer's disease: progress and problems on the road to therapeutics[J]. Science, 2002, 297(5580): 353-356.[26] 沈颖华, 殷明. 烟碱型乙酰胆碱受体的激动与阿尔茨海默病的治疗[J]. 解放军药学学报, 2008, 24(2): 159-162.[27] 戴婷婷, 田绍文. 阿尔兹海默病靶向治疗研究进展[J]. 中南医学科学杂志, 2015, 4: 452-456.[28] C M Flores, Rogers S W, Pabreza L A, et al. A subtype of nicotinic cholinergic receptor in rat brain is composed of alpha 4 and beta 2 subunits and is up-regulated by chronic nicotine treatment[J]. Molecular pharmacology, 1992, 41(1): 31.[29] Bruno Buisson, Daniel Bertrand. Chronic exposure to nicotine upregulates the human (alpha)4((beta)2 nicotinic acetylcholine receptor function[J]. J Neuroscience Official J Society for Neuroscience, 2001, 21(6): 1819-1829.[30] Yolanda F Vallejo, Bruno Buisson, Daniel Bertrand, et al. Chronic nicotine exposure upregulates nicotinic receptors by a novel mechanism[J]. J Neuroscience Official J Society for Neuroscience, 2005, 25(23): 5563-5572.[31] Hoau-Yan Wang, Lee D H, Michael Robert D'Andrea, et al. beta-Amyloid(1-42) binds to alpha7 nicotinic acetylcholine receptor with high affinity. Implications for Alzheimer's disease pathology[J]. J Biological Chemistry, 2000, 275(8): 5626-5632.[32] Chen Ling, Kiyofumi Yamada, Toshitaka Nabeshima, et al. alpha7 Nicotinic acetylcholine receptor as a target to rescue deficit in hippocampal LTP induction in beta-amyloid infused rats[J]. Neuropharmacology, 2006, 50(2): 254.[33] Qin Ryan, Amna Ibrahim, Martin H Cohen, et al. FDA drug approval summary: lapatinib in combination with capecitabine for previously treated metastatic breast cancer that overexpresses HER-2[J]. The Oncologist, 2008, 13(10): 1114-1119.[34] Ana Pocivavsek, Laura Icenogle, Edward D Levin. Ventral hippocampal α7 and α4β2 nicotinic receptor blockade and clozapine effects on memory in female rats[J]. Psychopharmacology, 2006, 188(4): 597-604.[35] C Fernandes, Hoyle E, Dempster E, et al. Performance deficit of α7 nicotinic receptor knockout mice in a delayed matching-to-place task suggests a mild impairment of working/episodic-like memory[J]. Genes Brain & Behavior, 2006, 5(6): 433.[36] Naoya Oishi, Kazuo Hashikawa, Hidefumi Yoshida, et al. Quantification of nicotinic acetylcholine receptors in Parkinson's disease with (123)I-5IA SPECT[J]. J Neurological Sciences, 2007, 256(1): 52-60.[37] Jennifer M Kulak, J Michael Mcintosh, Maryka Quik. Loss of nicotinic receptors in monkey striatum after 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine treatment is due to a decline in alpha-conotoxin MII sites[J]. Molecular Pharmacology, 1992, 2002, 61(1): 230-238.[38] Margaret R Spitz, Christopher I Amos, Dong Qiong, et al. The CHRNA5-A3 region on chromosome 15q24-25.1 is a risk factor both for nicotine dependence and for lung cancer[J]. J National Cancer Institute, 2008, 100(21): 1552.[39] Jen C Wang, Carlos Cruchaga, Nancy L Saccone, et al. Risk for nicotine dependence and lung cancer is conferred by mRNA expression levels and amino acid change in CHRNA5[J]. Human Molecular Genetics, 2009, 18(16): 3125-3135.[40] N L Benowitz. Pharmacology of nicotine: addiction, smoking-induced disease, and therapeutics[J]. Annual Review of Pharmacology & Toxicology, 2009, 49(1): 57-71.[41] Ma Reina D Improgo, Nicolette A Schlichting, Roxana Y Cortes, et al. ASCL1 regulates expression of the chrna5/a3/b4 lung cancer susceptibility locus[J]. Molecular Cancer Research, 2010, 8(2): 194-203.[42] David Chi-leung, Luc Girard, Ruben Ramirez, et al. Expression of nicotinic acetylcholine receptor subunit genes in non-small-cell lung cancer reveals differences between smokers and nonsmokers[J]. Cancer Research, 2007, 67(10): 4638-4647.[43] Herve Sartelet, Kamel Maouche, Jean-laurent Totobenazara, et al. Expression of nicotinic receptors in normal and tumoral pulmonary neuroendocrine cells (PNEC)[J]. Pathology Research & Practice, 2008, 204(12): 891.[44] Anupam Paliwal, Thomas Vaissière, Annette Krais, et al. Aberrant DNA methylation links cancer susceptibility locus 15q25.1 to apoptotic regulation and lung cancer[J]. Cancer Research, 2010, 70(7): 2779-2788.[45] Song Ping-fang, Harmanjatinder S Sekhon, Jia Yi-bing, et al. Acetylcholine is synthesized by and acts as an autocrine growth factor for small cell lung carcinoma[J]. Cancer Research, 2003, 63(1): 214-221.[46] Sergei Grando. Basic and clinical aspects of non-neuronal acetylcholine: biological and clinical significance of non-canonical ligands of epithelial nicotinic acetylcholine receptors[J]. J Pharmacol Sci, 2008, 106(2): 174-179.[47] Ma Reina Improgo, Lindsey G Soll, Andrew R Tapper, et al. Nicotinic acetylcholine receptors mediate lung cancer growth[J]. Frontiers in Physiology, 2012, 4(251): 1- 6.[48] 陆晶晶, 黄建浩, 尹琦, et al. 烟碱型乙酰胆碱受体基因多态性与NSCLC的相关性研究[J]. 同济大学学报: 医学版, 2016,( 3): 36-39.[49] Bhartimittu, Yashila Girdhar. Lung cancer and nicotine[J]. J Chromatogr Sep Tech, 2016, 7: 2.[50] T Nishioka, Luo L Y, Shen L, et al. Nicotine increases the resistance of lung cancer cells to cisplatin through enhancing Bcl-2 stability[J]. J British Cancer, 2014, 110(7): 1785-1792.[51] Jin Zhao-hui, Gao Feng-qin, Tammy Flagg, et al. Nicotine induces multi-site phosphorylation of Bad in association with suppression of apoptosis[J]. J Biological Chemistry, 2004, 279(22): 23837-23844.[52] Ma Reina Improgo, Andrew R Tapper, Paul D Gardner. Nicotinic acetylcholine receptor-mediated mechanisms in lung cancer[J]. Biochemical Pharmacology, 2011, 82(8): 1015-1021.[53] Si-qin Luo, Jennifer M Kulak, G Edward Cartier, et al. α-Conotoxin AuIB selectively blocks α3β4 nicotinic acetylcholine receptors and nicotine-evoked norepinephrine release[J]. J Neuroscience, 1998, 18(21): 8571- 8579.[54] Sulan Luo, Zhangsun Dong-ting, Zhu Xiao-peng, et al. Characterization of a novel alpha-conotoxin txid from conus textile that potently blocks rat alpha3beta4 nicotinic acetylcholine receptors[J]. J Medicinal Chemistry, 2011, 56(23): A-I.[55] Hai-ji Sun, Ma Xiao-li. α5-nAChR modulates nicotine-induced cell migration and invasion in A549 lung cancer cells[J]. Experimental & Toxicologic Pathology Official J Gesellschaft Fur Toxikologische Pathologie, 2015, 67(9): 477-482.[56] Anna Chikova, Sergei A Grando. Naturally occurring variants of human Α9 nicotinic receptor differentially affect bronchial cell proliferation and transformation[J]. Plos One, 2011, 6(11): e27978.[57] Richard D Egleton, Kathleen C Brown, Piyali Dasgupta. Nicotinic acetylcholine receptors in cancer: multiple roles in proliferation and inhibition of apoptosis[J]. Trends in Pharmacological Sciences, 2008, 29(3): 151.[58] Takashi Nishioka, Guo Jin-jin, Daisuke Yamamoto, et al. Nicotine, through upregulating pro-survival signaling, cooperates with NNK to promote transformation[J]. J Cellular Biochemistry, 2010, 109(1): 152–161.[59] Alexander I Chernyavsky, Juan Arredondo, Qian Jing, et al. Coupling of ionic events to protein kinase signaling cascades upon activation of alpha7 nicotinic receptor: cooperative regulation of alpha2-integrin expression and Rho kinase activity[J]. J Biological Chemistry, 2009, 284(33): 22140-22148.[60] Mina Kalantari-Dehaghi, Erinn A Parnell, Tara Armand, et al. The nicotinic acetylcholine receptor-mediated reciprocal effects of the tobacco nitrosamine NNK and SLURP-1 on human mammary epithelial cells[J]. International Immunopharmacology, 2015, 29(1): 99-104.[61] Chia-Hwa Lee, Ching-Shui Huang, Ching-Shyang Chen, et al. Overexpression and activation of the alpha9-nicotinic receptor during tumorigenesis in human breast epithelial cells[J]. J National Cancer Institute, 2010, 102(17): 1322-1335.[62] E X Albuquerque, Pereira E F R, Alkondon M, et al. Mammalian Nicotinic Acetylcholine Receptors: From Structure to Function[J]. Physiological Reviews, 2009, 89(1): 73-120.与1重复[63] Chih-Hsiung Wu, Chia-Hwa Lee, Yuan-Soon Ho. Nicotinic acetylcholine receptor-based blockade: applications of molecular targets for cancer therapy[J]. Clinical Cancer Research An Official J American Association for Cancer Research, 2011, 17(11): 3533-3541.[64] Shih-Hsin Tu, Ku Chung-yu, Ho Chi-tang, et al. Tea polyphenol (-)-epigallocatechin-3-gallate inhibits nicotine- and estrogen-induced α9-nicotinic acetylcholine receptor upregulation in human breast cancer cells[J]. Molecular Nutrition & Food Research, 2011, 55(3): 455-466.[65] Ching-Shyang Chen, Chia-Hwa Lee, Chang-da Hsieh, et al. Nicotine-induced human breast cancer cell proliferation attenuated by garcinol through down-regulation of the nicotinic receptor and cyclin D3 proteins[J]. Breast Cancer Research and Treatment, 2011, 125(1): 73-87.[66] Yung Leun Shih, Liu Hui-ching, Chen Ching Shyang, et al. Combination treatment with luteolin and quercetin enhances antiproliferative effects in nicotine-treated MDA-MB-231 cells by down-regulating nicotinic acetylcholine receptors[J]. J Agricultural & Food Chemistry, 2010, 58(1): 235-241.[67] Luo Su-lan, Dongting Zhangsun, Peta J Harvey, et al. Cloning, synthesis, and characterization of αO-conotoxin GeXIVA, a potent α9α10 nicotinic acetylcholine receptor antagonist[J]. Proceedings of the National Academy of Sciences USA, 2015, 112(30): 4026-4035.[68] Li Xiao-dan, Hu Yuan-yan, Wu Yong, et al. Anti-hypersensitive effect of intramuscular administration of αO-conotoxin GeXIVA[1,2] and GeXIVA[1,4] in rats of neuropathic pain[J]. Prog Neuropsychopharmacol Biol Psychiatry, 2016, 66: 112-119.[69] Mei Dong, Lin Zhi-qiang, Fu Ji-jun, et al. The use of α-conotoxin ImI to actualize the targeted delivery of paclitaxel micelles to α7 nAChR-overexpressing breast cancer[J]. Biomaterials, 2015, 42: 52-65.[70] Michael Ellison, Gao Fan, Wang Hai-long, et al. Alpha-conotoxins ImI and ImII target distinct regions of the human alpha7 nicotinic acetylcholine receptor and distinguish human nicotinic receptor subtypes[J]. Biochemistry, 2004, 43(51): 16019-16026.[71] Layla Azam, J Michael Mcintosh. Molecular basis for the differential sensitivity of rat and human α9α10 nAChRs to α-conotoxin RgIA[J]. J Neurochemistry, 2012, 122(6): 1137-1144.[72] Layla Azam, Athanasios Papakyriakou, Marios Zouridakis, et al. Molecular interaction of α-conotoxin RgIA with the rat α9α10 nicotinic acetylcholine receptor[J]. Molecular pharmacology, 2015, 87(5): 855-864.[73] Lorenzo Di Cesare Mannelli, Lorenzo Cinci, Laura Micheli, et al. α-Conotoxin RgIA protects against the development of nerve injury-induced chronic pain and prevents both neuronal and glial derangement[J]. Pain, 2014, 155(10): 1986-1995.[74] Michael Ellison, Christian Haberlandt, Maria Eugenia Gomez-Casati, et al. Alpha-RgIA: a novel conotoxin that specifically and potently blocks the alpha9alpha10 nAChR[J]. Biochemistry, 2006, 45(5): 1511-1517.[75] Haylie K Romero, Sean B Christensen, Lorenzo Di Cesare Mannelli, et al. Inhibition of α9α10 nicotinic acetylcholine receptors prevents chemotherapy-induced neuropathic pain[J]. Proceedings of the National academy of Sciences USA, 2017, 114 (10): E1825.[76] Sun Dan-dan, Ren Zheng-hua, Zeng Xia-yun, et al. Structure–function relationship of conotoxin lt14a, a potential analgesic with low cytotoxicity[J]. Peptides, 2011, 32(2): 300-305.[77] Can Peng, Tang Shao-jun, Pi Can-hui, et al. Discovery of a novel class of conotoxin from Conus litteratus , lt14a, with a unique cysteine pattern[J]. Peptides, 2006, 27(9): 2174-2181.[78] Sulan Luo, Zhangsun Dongting, Zhu Xiao-peng, et al. Characterization of a novel α-conotoxin TxID from Conus textile that potently blocks rat α3β4 nicotinic acetylcholine receptors[J]. J Medicinal Chemistry, 2013, 288(2): 894-902.[79] Valentin A Pavlov, Wang Hong, Christopher J Czura, et al. The cholinergic anti-inflammatory pathway[J]. Brain Behavior & Immunity, 2005, 19(6): 493-499.[80] Lyudmila V Borovikova, Svetlana Ivanova, Zhang Ming-huang, et al. Vagus nerve stimulation attenuates the systemic inflammatory response to endotoxin[J]. Nature, 2000, 405(6785): 458-462.[81] Hong Wang, Yu Man, Mahendar Ochani, et al. Nicotinic acetylcholine receptor |[alpha]|7 subunit is an essential regulator of inflammation[J]. Nature, 2003, 421(6921): 384-388.[82] 张琴, 喻文亮. 胆碱能抗炎通路研究进展[J]. 中国免疫学杂志, 2012, 28(11): 1054-1056. |
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