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1.
The combinative rate measurement of (3-[Ⅰ125] iodotyrosyl) α-bungarotoxin was applied in the analysis of the relation between nerve acetylcholine receptor and three types of insecticide resistance in diamondback moth, Plutella xylostella (L.). In the dimehypo-resistant strain and in the cartap-resistant strain, the nerve acetylcholine receptor showed the remarkable insensitivity to dimehypo and cartap, of which the binding rate to ligand was approximately 66 and 60%, respectively, of the susceptible strain. The sensitivity to deltamethrin in the deltamethrin-resistant strain did not show visible change. These results indicated that the decline in the sensitivity of nerve acetylcholine receptor to insecticide might be a potential mechanism to nereistoxin insecticides resistance in the diamondback moth. 相似文献
2.
The combinative rate measurement of （3-[I125] iodotyrosyl） α-bungarotoxin was applied in the analysis of the relation between nerve acetylcholine receptor and three types of insecticide resistance in diamondback moth, Plutella xylostella （L.）. In the dimehypo-resistant strain and in the cartap-resistant strain, the nerve acetylcholine receptor showed the remarkable insensitivity to dimehypo and cartap, of which the binding rate to ligand was approximately 66 and 60%, respectively, of the susceptible strain. The sensitivity to deltamethrin in the deltamethrin-resistant strain did not show visible change. These results indicated that the decline in the sensitivity of nerve acetylcholine receptor to insecticide might be a potential mechanism to nereistoxin insecticides resistance in the diamondback moth. 相似文献
3.
小菜蛾nAChR靶标敏感性与沙蚕毒素类药物的抗性关系 总被引：1，自引：0，他引：1
【目的】研究抗杀虫双、杀螟丹和溴氰菊酯品系的神经乙酰胆碱受体及与它们对沙蚕毒素类药物的抗性间的关系。【方法】测定不同品系小菜蛾的神经乙酰胆碱受体与125I标记的α-银环蛇毒素的结合率。【结果】抗杀虫双、杀螟丹品系小菜蛾的神经乙酰胆碱受体对沙蚕毒素药物有显著的靶标不敏感性,它们与配体的结合率大约分别是敏感品系的66%和60%,在溴氰菊酯抗性品系中没有明显变化。【结论】神经乙酰胆碱受体对杀虫剂敏感性下降可能是小菜蛾对沙蚕毒素药物产生抗性的一种作用机理。 相似文献
4.
Amino acid sequence similarity between rabies virus glycoprotein and snake venom curaremimetic neurotoxins 总被引：8，自引：0，他引：8
Evidence was presented earlier that a host-cell receptor for the highly neurotropic rabies virus might be the acetylcholine receptor. The amino acid sequence of the glycoprotein of rabies virus was compared by computer analysis with that of snake venom curaremimetic neurotoxins, potent ligands of the acetylcholine receptor. A statistically significant sequence relation was found between a segment of the rabies glycoprotein and the entire sequence of long neurotoxins. The greatest identity occurs with residues considered most important in neurotoxicity, including those interacting with the acetylcholine binding site of the acetylcholine receptor. Because of the similarity between the glycoprotein and the receptor-binding region of the neurotoxins, this region of the viral glycoprotein may function as a recognition site for the acetylcholine receptor. Direct binding of the rabies virus glycoprotein to the acetylcholine receptor could contribute to the neurotropism of this virus. 相似文献
5.
Parasympathetic innervation maintains epithelial progenitor cells during salivary organogenesis 总被引：1，自引：0，他引：1
Knox SM Lombaert IM Reed X Vitale-Cross L Gutkind JS Hoffman MP 《Science (New York, N.Y.)》2010,329(5999):1645-1647
The maintenance of a progenitor cell population as a reservoir of undifferentiated cells is required for organ development and regeneration. However, the mechanisms by which epithelial progenitor cells are maintained during organogenesis are poorly understood. We report that removal of the parasympathetic ganglion in mouse explant organ culture decreased the number and morphogenesis of keratin 5-positive epithelial progenitor cells. These effects were rescued with an acetylcholine analog. We demonstrate that acetylcholine signaling, via the muscarinic M1 receptor and epidermal growth factor receptor, increased epithelial morphogenesis and proliferation of the keratin 5-positive progenitor cells. Parasympathetic innervation maintained the epithelial progenitor cell population in an undifferentiated state, which was required for organogenesis. This mechanism for epithelial progenitor cell maintenance may be targeted for organ repair or regeneration. 相似文献
6.
Fertilization events induced by neurotransmitters after injection of mRNA in Xenopus eggs 总被引：12，自引：0，他引：12
D Kline L Simoncini G Mandel R A Maue R T Kado L A Jaffe 《Science (New York, N.Y.)》1988,241(4864):464-467
Fertilization initiates in the egg a dramatic increase in intracellular calcium that opens ion channels and causes exocytosis. To explore the possibility that these events might involve a receptor-mediated pathway, receptors for serotonin or acetylcholine (M1 muscarinic) were expressed in the Xenopus egg; serotonin or acetylcholine then could initiate a series of responses similar to those normally initiated by sperm. Thus, there may be an endogenous receptor in the egg membrane that is activated by sperm, and the serotonin or M1 muscarinic receptor may replace the sperm receptor in this pathway. 相似文献
7.
Acetylcholine receptor synthesis in retina and transport to optic tectum in goldfish 总被引：4，自引：0，他引：4
Previous studies have suggested that the retinotectal system of the goldfish contains a nicotinic acetylcholine receptor (nAChR) that is sensitive to alpha-bungarotoxin. Extracellularly recorded field potentials elicited in response to visual stimulation can be blocked by alpha-bungarotoxin, and alpha-bungarotoxin can interfere with the maintenance of retinotectal synaptic connections. Whether the transmission between the retinal ganglion cells and the tectal cells is mediated by acetylcholine and whether nAChR's exist on the dendrites of tectal cells are questions that remain. The experiments described in this report were designed to determine the site of synthesis of the nAChR's associated with the goldfish retinotectal projection. Radioactive (35S-labeled) methionine was injected into either the eye or the tectal ventricle, and the incorporation of radioactivity into the nAChR was measured by immunoprecipitation. The use of this technique provides evidence that an nAChR associated with the goldfish retinotectal projection is synthesized in the retina and transported to the optic tectum, which suggests a presynaptic site of acetylcholine action on retinal terminals. 相似文献
8.
Rosas-Ballina M Olofsson PS Ochani M Valdés-Ferrer SI Levine YA Reardon C Tusche MW Pavlov VA Andersson U Chavan S Mak TW Tracey KJ 《Science (New York, N.Y.)》2011,334(6052):98-101
Neural circuits regulate cytokine production to prevent potentially damaging inflammation. A prototypical vagus nerve circuit, the inflammatory reflex, inhibits tumor necrosis factor-α production in spleen by a mechanism requiring acetylcholine signaling through the α7 nicotinic acetylcholine receptor expressed on cytokine-producing macrophages. Nerve fibers in spleen lack the enzymatic machinery necessary for acetylcholine production; therefore, how does this neural circuit terminate in cholinergic signaling? We identified an acetylcholine-producing, memory phenotype T cell population in mice that is integral to the inflammatory reflex. These acetylcholine-producing T cells are required for inhibition of cytokine production by vagus nerve stimulation. Thus, action potentials originating in the vagus nerve regulate T cells, which in turn produce the neurotransmitter, acetylcholine, required to control innate immune responses. 相似文献
9.
Interpenetration (catenation) has long been considered a major impediment in the achievement of stable and porous crystalline structures. A strategy for the design of highly porous and structurally stable networks makes use of metal-organic building blocks that can be assembled on a triply periodic P-minimal geometric surface to produce structures that are interpenetrating-more accurately considered as interwoven. We used 4,4',4"-benzene-1,3,5-triyl-tribenzoic acid (H(3)BTB), copper(II) nitrate, and N,N'-dimethylformamide (DMF) to prepare Cu(3)(BTB)(2)(H(2)O)(3).(DMF)(9)(H(2)O)(2) (MOF-14), whose structure reveals a pair of interwoven metal-organic frameworks that are mutually reinforced. The structure contains remarkably large pores, 16.4 angstroms in diameter, in which voluminous amounts of gases and organic solvents can be reversibly sorbed. 相似文献
10.
Okada K Inoue A Okada M Murata Y Kakuta S Jigami T Kubo S Shiraishi H Eguchi K Motomura M Akiyama T Iwakura Y Higuchi O Yamanashi Y 《Science (New York, N.Y.)》2006,312(5781):1802-1805
The formation of the neuromuscular synapse requires muscle-specific receptor kinase (MuSK) to orchestrate postsynaptic differentiation, including the clustering of receptors for the neurotransmitter acetylcholine. Upon innervation, neural agrin activates MuSK to establish the postsynaptic apparatus, although agrin-independent formation of neuromuscular synapses can also occur experimentally in the absence of neurotransmission. Dok-7, a MuSK-interacting cytoplasmic protein, is essential for MuSK activation in cultured myotubes; in particular, the Dok-7 phosphotyrosine-binding domain and its target in MuSK are indispensable. Mice lacking Dok-7 formed neither acetylcholine receptor clusters nor neuromuscular synapses. Thus, Dok-7 is essential for neuromuscular synaptogenesis through its interaction with MuSK. 相似文献
11.
Genetic reconstitution of functional acetylcholine receptor channels in mouse fibroblasts 总被引：12，自引：0，他引：12
T Claudio W N Green D S Hartman D Hayden H L Paulson F J Sigworth S M Sine A Swedlund 《Science (New York, N.Y.)》1987,238(4834):1688-1694
Foreign genes can be stably integrated into the genome of a cell by means of DNA-mediated gene transfer techniques, and large quantities of homogenous cells that continuously express these gene products can then be isolated. Such an expression system can be used to study the functional consequences of introducing specific mutations into genes and to study the expressed protein in the absence of cellular components with which it is normally in contact. All four Torpedo acetylcholine receptor (AChR) subunit complementary DNA's were introduced into the genome of a mouse fibroblast cell by DNA-mediated gene transfer. A clonal cell line that stably produced high concentrations of correctly assembled cell surface AChR's and formed proper ligand-gated ion channels was isolated. With this new expression system, recombinant DNA, biochemical, pharmacological, and electrophysiological techniques were combined to study Torpedo AChR's in a single intact system. The physiological and pharmacological profiles of Torpedo AChR's expressed in mouse fibroblast cells differ in some details from those described earlier, and may provide a more accurate reflection of the properties of this receptor in its natural environment. 相似文献
12.
Mapping the main immunogenic region and toxin-binding site of the nicotinic acetylcholine receptor 总被引：30，自引：0，他引：30
T Barkas A Mauron B Roth C Alliod S J Tzartos M Ballivet 《Science (New York, N.Y.)》1987,235(4784):77-80
The alpha-chain of the nicotinic acetylcholine receptor carries the binding sites both for cholinergic ligands and for most experimentally induced or naturally occurring antibodies to the native receptor. By means of expression cloning in Escherichia coli, fusion proteins were derived from specific fragments of a complementary DNA encoding the mouse alpha-chain, allowing the mapping of the toxin-binding site to residues 160-216 and the main immunogenic region to residues 6-85. This approach permits the independent study of different functional domains of a complex receptor molecule and should be generally applicable to other proteins for which complementary DNA clones are available. 相似文献
13.
Direct activation of mammalian atrial muscarinic potassium channels by GTP regulatory protein Gk 总被引：41，自引：0，他引：41
The mammalian heart rate is regulated by the vagus nerve, which acts via muscarinic acetylcholine receptors to cause hyperpolarization of atrial pacemaker cells. The hyperpolarization is produced by the opening of potassium channels and involves an intermediary guanosine triphosphate-binding regulatory (G) protein. Potassium channels in isolated, inside-out patches of membranes from atrial cells now are shown to be activated by a purified pertussis toxin-sensitive G protein of subunit composition alpha beta gamma, with an alpha subunit of 40,000 daltons. Thus, mammalian atrial muscarinic potassium channels are activated directly by a G protein, not indirectly through a cascade of intermediary events. The G protein regulating these channels is identified as a potent Gk; it is active at 0.2 to 1 pM. Thus, proteins other than enzymes can be under control of receptor coupling G proteins. 相似文献
14.
The complex Ni[S2C2(CF3)2]2 reacts with light olefins, including ethylene and propylene, selectively and reversibly. The reaction is not poisoned by hydrogen gas, carbon monoxide, acetylene, or hydrogen sulfide, which are commonly present in olefin streams, presumably because olefin binding occurs through the sulfur ligand rather than the metal center. The reversible reaction of olefins with Ni[S2C2(CN)2]2n (n = 0, -1, -2) can be controlled electrochemically, where the oxidation state-dependent binding and release of olefins are fast on the electrochemical time scale. The observed tolerance to poisons and controllable electrochemical reactivity present an alternative approach to the separation of olefins from complex streams. 相似文献
15.
为了进一步探究第11位氨基酸的性质对LvIA靶点结合活性的影响，设计了LvIA的2个新型突变体[D11R]LvIA和[D11H]LvIA，即用2个碱性氨基酸?精氨酸（R）和组氨酸（H）分别替换原来的酸性氨基酸D。先人工合成了这2个新突变体的线性肽，然后采用2步氧化法进行折叠，以获得在第1位和第3位半胱氨酸（Cys 1～3）、第2位和第4位半胱氨酸（Cys 2～4）之间定点连接形成二硫键。经高效液相色谱分离纯化和质谱鉴定，合成了含有Cys(1～3, 2～4)二硫键连接方式的多肽，其分子质量正确，纯度在95%以上。利用双电极电压钳电生理学技术对这2种突变体与α3β2 nAChR的结合活性进行了检测。结果发现，当该位点的氨基酸性质由酸性转换为碱性后，对LvIA的活性影响巨大，直接导致对α3β2 nAChR的阻断活性丧失。[D11R]LvIA和[D11H]LvIA的活性与野生型LvIA相比分别降低了574.38%和408.62%。由此表明，第11位氨基酸的酸碱性对LvIA的活性至关重要。 相似文献
16.
Molecular biology of synaptic receptors 总被引：18，自引：0，他引：18
E De Robertis 《Science (New York, N.Y.)》1971,171(975):963-971
A special proteolipid (a hydrophobic protein) has been extracted and purified from nerve-ending membranes and total particulate matter of gray areas of the central nervous system. Such a proteolipid shows a high affinity for binding d-tubocurarine, serotonin, and atropine and has been called receptor proteolipid. The interaction of this proteolipid with atropine sulfate was studied with light scattering and polarization of fluorescence. The changes observed, which follow a cooperative type of curve, were attributed to the aggregation of the proteolipid macromolecules. Such a phenomenon was then observed under the electron microscope. A receptor proteolipid having a high affinity for binding acetylcholine, hexamethonium, and other cholinergic drugs was isolated and purified from electric tissue of fishes and from electroplax membranes. Such a proteolipid was also extracted from membranes from which acetylcholinesterase had been removed, and it was concluded that this enzyme and the receptor proteolipid are two different macromolecules. A high affinity binding site with a dissociation constant of K1 equal to 10(-7) and about ten sites with K2 equal to 10(-5) were recognized in the receptor proteolipid. Under the electron microscope the receptor proteolipid of brain appears as a rod-shaped macromolecule which may assume paracrystalline arrays with 10(-8) molar atropine sulfate. Similarly the receptor proteolipid from electric tissue and from skeletal muscle may form paracrystalline arrays under the action of acetylcholine and hexamethonium. A model of the cholinergic receptor based on the properties of the proteolipid is presented. Preliminary work indicates the possibility of obtaining a biophysical response to acetylcholine when the receptor proteolipid is embedded in artificial bilayered lipid membrance. 相似文献
17.
Amantadine: neuromuscular blockade by suppression of ionic conductance of the acetylcholine receptor 总被引：5，自引：0，他引：5
E X Albuquerque A T Eldefrawi M E Eldefrawi N A Mansour M C Tsai 《Science (New York, N.Y.)》1978,199(4330):788-790
Amantadine hydrochloride decreases the sensitivity of denervated mammalian muscle to iontophoretically applied acetylcholine. The drug depresses the amplitude of the end-plate current and reverses the slope of the relation between half-decay time and membrane potential suggesting that it alters the ionic conductance that is mediated by the acetylcholine receptor. Binding studies confirm that amantadine acts on the ion conductance modulator rather than the acetylcholine receptor. 相似文献
18.
Acetylcholine receptor: an allosteric protein 总被引：51，自引：0，他引：51
The nicotine receptor for the neurotransmitter acetylcholine is an allosteric protein composed of four different subunits assembled in a transmembrane pentamer alpha 2 beta gamma delta. The protein carries two acetylcholine sites at the level of the alpha subunits and contains the ion channel. The complete sequence of the four subunits is known. The membrane-bound protein undergoes conformational transitions that regulate the opening of the ion channel and are affected by various categories of pharmacologically active ligands. 相似文献
19.
吡虫啉作为一种新型高效烟碱类杀虫剂,被广泛投入市场使用。该药剂主要作用于昆虫的乙酰胆碱受体,具有杀虫谱广、活性高、用量少、持效长、对非靶标生物较安全等特点。本研究综述了吡虫啉残留的危害性及几种有效的降解途径,对寻找一种环保、高效的消除或降解农药残留的方法具有一定指导意义。 相似文献
20.
Synthetic amphiphilic peptide models for protein ion channels 总被引：32，自引：0，他引：32
Ion channel proteins are important for the conduction of ions across biological membranes. Recent analyses of their sequences have suggested that they are composed of bundles of alpha-helices that associate to form ion-conducting channels. To gain insight into the mechanisms by which alpha-helices can aggregate and conduct ions, three model peptides containing only leucine and serine residues were synthesized and characterized. A 21-residue peptide, H2N-(Leu-Ser-Ser-Leu-Leu-Ser-Leu)3-CONH2, which was designed to be a membrane-spanning amphiphilic alpha-helix, formed well-defined ion channels with ion permeability and lifetime characteristics resembling the acetylcholine receptor. In contrast, a 14-residue version of this peptide, which was too short to span the phospolipid bilayer as an alpha-helix, failed to form discrete, stable channels. A third peptide, H2N-(Leu-Ser-Leu-Leu-Leu-Ser-Leu)3-CONH2, in which one serine per heptad repeat was replaced by leucine, produced proton-selective channels. Computer graphics and energy minimization were used to create molecular models that were consistent with the observed properties of the channels. 相似文献