烟碱乙酰胆碱受体及其与新烟碱类相互作用的研究进展

唐振华; 陶黎明; 李忠

烟碱乙酰胆碱受体及其与新烟碱类相互作用的研究进展

1.
华东理工大学药学院, 上海 200237
2.
中国科学院上海植物生理生态研究所,上海 200032
3.
上海市农药研究所,上海 200032

基金项目:

国家重点基础研究发展规划(973计划)(2003CB114403).

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出版历程
- 收稿日期: 2007-03-21

Advances in Nicotinic Acetylcholine Receptors and their Interactions with Neonicotinoids

1.
School of Pharmacy,East China University of Science and Technology,Shanghai 200237,China
2.
Shanghai Institute of Plant Physiology and Ecology,Chinese Academy of Sciences,Shanghai 200032,China
3.
Shanghai Pesticide Research Institute,Shanghai 200032,China

摘要

摘要: 对烟碱乙酰胆碱受体(nAChRs)的结构与功能、配体结合部位、门控机理以及与新烟碱类的相互作用进行了综述,并对nAChRs亚基基因突变和敲除对新烟碱类和多杀菌素敏感性的影响进行了讨论。nAChRs在脊椎动物和昆虫的胆碱能突触的快速神经传递中起着重要作用,其在昆虫中仅存在于中枢神经系统(CNS)中,而在脊椎动物中同时存在于CNS和神经肌肉连接处。nAChRs是新烟碱类杀虫剂、多杀菌素和杀螟丹的作用靶标。肌肉和CNS中的nAChRs是一个由两个α和三个非α(β,γ和δ)亚基组成的异数五聚体,该受体主要有三部分:一个在细胞外发现的区域(胞外区)、一个位于膜内的区域(跨膜区),另一个是位于细胞内的区域(胞质区)。每个亚基(从N-C端)都具有一个包含乙酰胆碱(ACh)结合部位的细胞外结构域;4个跨膜结构域(M1~4),其中M2的大部分氨基酸位于离子通道的内壁;一个胞质噜扑(loop)和一个胞外C端。通道门位于孔道内的疏水区。ACh结合部位位于天然和功能受体的两个亚基的界面,是由一个亚基的3个噜扑(A-C)和另一个亚基的3个噜扑(D-F)构成。每当受体与ACh(或其他激动剂)分子结合时,M2 α螺旋体的构象发生改变,使通道开启,处于阳离子传导状态,直至一个或两个激动剂分子从结合口袋解离,通道才关闭。如果激动剂一直存在,并反复结合,则通道处于脱敏状态。nAChRs与新烟碱类的各种选择性作用取决于新烟碱类的结构以及nAChRs的亚基组成。
- 烟碱乙酰胆碱受体(nAChRs) /
- 结构与功能 /
- 门控机理 /
- 与新烟碱类的相互作用
Abstract: The structure and function of nAChRs,ligand-binding sites,gating mechanism and interactions with neonicotinoids were reviewed.Effects of mutations and knockout of subunit genes on the sensitivity to neonicotinoids and spinosad were also discussed.The nAChRs play an essential role in the fast excitatory neurotransmission at cholinergic synapses in both vertebrates and insects.However,nAChRs are confined to the central nervous system (CNS) in insects,unlike in vertebrates where they are also found in neuromuscular junctions.The nAChRs are the target site for the neonicotinoids,spinosad ,as well as cartap.The nAChR,both in muscle and CNS,is a heteromeric pentamer composed of five subunits,typically 2 α and 3 non-α (β,γ and δ).The receptor has three main parts: a region found outside of the cell (extracellular),a region located within the membrane (transmembrane),and an intracellular portion (cytoplasmic).Each of the five subunits is composed of (from N-C terminus) an extracellular domain that includes the acetylcholine (ACh) binding site,four transmembrane domains (M1- 4) with M2 contributing most of the amino acids that line the ion channel,a cytoplassmic loop and an extracellular C-terminus.The channel's gate is expected to located in hydrophobic regions within the pore.The ACh binding site,in native and functional receptors,is located at the interface of two subunits,and possibly composed by three loops (loops A-C) of one subunit and three loops( D-F) of the other subunit.Upon binding the molecules of ACh (or other agonists),the receptor undergoes a conformational change that places the M2 α-helices in the opening,cation-conducting state.The channel remains open before one or both agonist molecules dissociate from the binding pocket and then the channel closes.If the agonist presents and binds repeatedly,the channel would enter a desensitized state.The diverse selective interactions of nAChRs with neonicotinoids depend on the structure of neonicotinoids as well as the subunit composition of the nAChRs.
- nicotinic acetylcholine receptors (nAChRs) /
- structure and function /
- gating mechanism /
- interactions with neonicotinoids

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参考文献(42)

MILLAR N S,DENHOLM I.Nicotinic Acetylcholine Receptors: Targets for Commercially Important Insecticides[J]. Invert Neurosci,2007,7: 53-66.

RODRIGUES-PINGUET N O.Nicotinic Acetylcholine Receptors [M]//Lennarz W J,Lane M D.Encyclopedia of Biological Biochemisty.Boston: Elsevier.2004,3 (N-R):57-61.

TOMIZAWA M,CASISDA J E.Selective Toxicity of Neonicotinoids Attribution to Specificity of Insect and Mammalian Nicotinic Receptors [J].Ann Rev Entomol,2003,48:339-364.

MATSUDA K,BUCKINGHAM S,KLEIER D,et al. Neonicotinoids: Insecticides Acting on Insect Nicotinic Acetylcholine Receptors[J].Trends Pharmacol Sci, 2001,22:573-580.

TOMIZAWA M,MILLAR N S,CASIDA J E,et al.Pharmacological Profiles of Recombinant and Native Insect Nicotinic Acetylcholine Receptors [J].Insect Biochem Mol Biol,2005,35:1347-1355.

TANG Zhen-hua(唐振华),BI Qian(毕强).Molecular Behavior of Insecticide Action(杀虫剂作用的分子行为)[M].Shanghai(上海): Far-east Publishing House(远东出版社),2003:591-619.

TOMIZAWA M,CASISDA J E.Neonicotinoid Insecticides Toxicology: Mechanisms of Selective Action [J]. Annu Rev Pharmacol Toxicol,2005,45: 247-268.

MATSUDA K,SHIMOMURA M,IHARA M,et al. Neonicotinoids Show Selective and Diverse Actions on their Nicotinic Receptor Targets: Electrophysiology,Molecular Biology,and Receptor Modeling Studies [J].Biosci Biotechnol Biochem,2005,69:1442-1452.

YAMAMOTO I,YABUTA G,TOMIZAWA M,et al. Molecular Mechanism for Selective Toxicity of Nicotinoids and Neonicotinoids [J].J Pestic Sci,1995,20:33-40.

TOMIZAWA M,LEE D L,CASIDA J E.Neonicotinoid Insecticides: Molecular Features Conferring Selectivity for Insect Versus Mammalian Nicotinic Receptor[J].Agric Food Chem,2000,48:6016-6024.

TANG Zhen-hua(唐振华),TAO Li-ming(陶黎明),LI Zhong(李忠).新烟碱类杀虫剂选择作用的分子机理[J].Chin J Pestic Sci (农药学学报),2006,8(4):291-298.

NAUEN R,DENHOLM I.Resistance of Insect Pests to Neonicotinoid Insecticides: Current Status and Future Prospects [J].Arch Insect Biochem Physiol,2005,58:200-215.

TANG Zhen-hua(唐振华),TAO Li-ming(陶黎明),LI Zhong(李忠).害虫对新烟碱类杀虫剂的抗药性及其治理对策[J].Chin J Pestic Sci (农药学学报),2006,8(2):85-87.

SINE S M,ENGEL A G.Recent Advances in Cys-loop Receptor Structure and Function [J].Nature,2006,440:448-455.

CHANGEUX J P.Functional Architecture and Dynamics of the Nicotinic Acetylcholine Receptor:A Ligand-Gated Ion Channel [J].Fidia Res Found Neurosi Award Lect,1991,4:21-168.

ADAMS M D,CELNIKER S E,HOLT R A,et al.The Genome Sequences of Drosophila melanogastr [J].Science,2000,287(5461): 2185-2195.

JONES A K,GRAUSO M,SATTELLE D B.The Nicotinic Acetylcholine Receptor Gene Family of the Malaria Mosquito,Anopheles gambiae [J].Genomics,2005,85:176-185.

JONES A K,RAYMOND-DELPECH V,THANY S H,et al.The Nicotinic Acetylcholine Receptor Gene Family of the Honey Bee,Apis mellifera [J].Genome Res,2006,16:1422-1430.

LIU Z W,WILLIAMSON M S,LANSDELL S J,et al.A nicotinic Acetylcholine Receptor Mutation Conferring Target-Site Resistance to Imidacloprid in Nilaparvata lugens (Brown Planthopper) [J].PNAS,2005,24:8420-8425.`

JONES A K,BROWN L A,SATTELLE D B.Insect Nicotinic Acetylcholine Receptor Gene Families: From Genetic Model Organism to Vector,Pest and Beneficial Species [J].Invert Neurosci,2007,7:67-73.

UNWIN N.Structure of the Acetylcholine-gated Channel [J].The Roy Soc,2002,355:1813-1829.

BREJC K,van DIJK W J,KLAASSEN R V,et al.Crystal Structure of an ACh-binding Protein Reveals the Ligand-Binding Domain of Nicotinic Receptors [J].Nature,2001,411:269-276

CORRINGER P J,NOVERE N L,CHANGEUX J P.Nicotinic Receptor at the Amino Acid Level[J].Ann Rev Pharmacol,2000,40:431-458.

MIYAZAWA A,FUJIYOSHI Y,UNWIN N.Structure and Gating Mechanism of the Acetylcholine Receptor Pore [J].Nature,2003,423: 949-955.

GALZI J L,CHANGEUX J P.Neurotransmitter-gated Ion Channels as Unconventional Allosteric Proteins[J].Curr Opin Struc Biol,1994,4: 554-565.

LEE S J,TOMIZAWA M,CASIDA J E.Neristoxin and Cartap Neurotoxicity Attributable to Direct Block of Insect Nicotinic Receptor/Channel[J].J Agric Food Chem,2003,57:2646-2652.

PATERSON D,NORDBERG D.Neuronal Nicotinic Receptors in the Human Brain[J].Prog Neurobiol,2000,61:75-111.

IHARA M,MATSUDA K,SHIMOMURA M,et al.Super Agonist Actions of Clothianidin and Related Compound on the ALSβ2 Nicotinic Acetylcholine Receptors Expressed in Xenopus laevis oocytes [J].Biosci Biotechnol Biochem,2004,68:761-763.

BROWN L A,IHARA M,BUCKINGHAM S D,et al.Neonicotinoid Insecticides Display Partial and Super Agonist Actions on Native Insect Nicotinic Acetylcholine Receptors[J].J Neurochem,2006,99:608-615.

SHIMOMURA M,SATOH H,YOKOTA M,et al.Insect-vertebrate Chimeric Nicotinic Acetylcholine Receptors Identify a Region,Loop B to the N-Terminus of the Drosophila Dα2 Subunit,which Contributes to Neonicotinoid Sensitivity [J].Neurosci Lett,2005,385:168-172.

MATSUDA K,BUCKINGHAM S D,FREEMAN J C,et al.Effects of the α Subunit on Imidacloprid Sensitivity of Recombinant Nicotinic Acetylcholine Receptors[J].Br J Pharmacol,1998,123:518-524.

IHARA M,MATSUDA K,OTAKE M,et al,Diverse Actions of Neonicotinoids on Chicken α 7,α 4β2 and Drosophila-chicken SADβ2 and ALSβ2 Hybrid Nicotinic Acetylcholine Receptors Expressed in Xenopus laevis oocytes [J].Neuropharmacology,2003,45:133-144.

SHIMOMURA M,YOKOTA M,MATSUDA K,et al.Roles of Loop C and the Loop B-C Interval of the Nicotinic Receptor α Subunit in its Selective Interactions with Imidacloprid in Insects[J].Neurosci Lett,2004,363:195-198。

LIU Z W,WILLIAMSON M S,LANSDELL S J,et al. A Nicotinic Acetylcholine Receptor Mutation (Y151S) Causes Reduced Agonist Potency to a Range of Neonicotinoid Insecticides [J].J Neurochem,2006,99: 1273-1281.

SALGADO V L,SPARKS T C.The Spinosyns: Chemistry,Biochemistry,Mode of Action,and Resistance [M] //GILBERT L I,IATROU K ,GILL S S.Comprehensive Molecular Insect Science,Boston: Elsevier,2005: 137-173.

ORR N,HASLER J,WATSON G,et al.Spinosad: From Nature to Green Chemistry to Novel Mode of Action //11^th IUPAC International Congress of Pesticide Chemistry Abstracts(1).Kobe,Japan: 2006:27.

PERRY T,MCKENZIE J A,BATTERHAM P.A Dα6 Knockout Strain of Drosophila melanogaster Confers a High Level of Resistance to Spinosad [J].Insect Biochem Molec Biol,2007,37: 184-188.

GAO J R,DEACUTIS J M,SCOTT J G.The Nicotinic Acetylcholine Receptor Subunit Md α6 from Musca domestica is Diversified Via Post-Transcriptional Modification [J].Insect Mol Biol,2007,16(3):325-334.

SATTELLE D B,JONES A K,SATTELLE B M,et al. Edit,Cut and Paste in the Nicotinic Acetylcholine Receptor Gene Family of Drosophila melanogaster [J].Bioassays,2005,27:366-376.

SHOJI H,TAKAHASHI,N,NOMOTO H,et al.Detailed Structural Analysis of Asparagine-linked Oligosaccharides of the Nicotinic Acetylene Receptor from Torpedo califormica [J].Eur J Biochem,1992,207: 631-641.

HUCHO F,TSETLIN V I,MACHOLD J.The Emerging Three-Dimensional Structure of a Receptor: The Nicotinic Acetylcholine Receptor [J].Eur J Biochem,1996,239:539-557.

UNWIN N.Refined Structure of the Nicotinic Acetylcholine Receptor at 4 Resolution [J].J Mol Biol,2005,346-967-989. (Ed.JIN S H)

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