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Research Article

The molecular basis of the structure and function of the 5-HT 3 receptor: a model ligand-gated ion channel (Review)

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Pages 11-26 | Published online: 09 Jul 2009

  • Adams, D. J., Dwyer, T. M and HiIIe, B., 1980, The permeabiity of endplate channels to monovalent and divalent metal cations. Journal General Physiology, 75, 433-510.
  • Aidley, D. J. and Stanfield, P. R., 1996, ton channels: molecules in action (Cambridge: Cambridge University Press).
  • Akabas, IvI H., Kaufmann, C., Archdeacon, P. and Karin, A., 1994, Identification of acelylchoine receptor channel-lining residues in the entire M2 segment of the a-subunit. Neuron, 13, 919-927.
  • Akabas, M K, Stauffer, D. A. Xu, M and Karin, A., 1992, Acetylcholine receptor channel structure probed in cysteriesubstilution mutants. Science, 258, 307-310.
  • Akk, G. and Auerbach, A., 1996, Inorganic, monovalent cations compete with agonists for the transmitter binding site of nicotinic acelylchoine receptors. Biophysical Joumal, 70, 2652-2658.
  • Amin, J. and Webs, D. S., 1993, GABAA receptor needs two homologous domains of the beta-subunit for activation by GABA but not by pentobarfahal. Nature, 366, 565-569.
  • Aqvist, J. and Luzhkov, V., 2000, Ion permeation mechanism of the potassium channel. Mature, 404, 881-884.
  • Arias, H. R., 1999, Role of local anesthetics on both cholnergic and serotonergic ionotropic receptors. Neuroscience and Biobehavioral Reviews. 23, 817-843.
  • Barann, M, Gothert, M, Bonisch, H., Dybek, A. and Urban, B. W., 1997, 5-HT3 receptors in outside-out patches of N1E-115 neuroblastcma cellsi basic properties and effects of pentobarbitaI. Neuropharmacology, 36, 655-664.
  • Barann, M, Gothert, M, Fink, K. and Bonisch, H., 1993, Inhibition by anaesthetics of 14C-guanidriium flux through the voltage-gated sodium channel and the cation channel of the 5-HT3 receptor of N1E-115 neuroblastoma cells. Naunyn Schmiedebergs Archives of Pharmacology. 347,125-132.
  • Barann, M, Ruppert, K., Gothert, IvI and Bonisch, H., 1995, Increasing effect of ethanol on 5-HT3 receptor-mediated 14Cguanidinun influx in N1E-115 neuroblastoma cells. Naunyn Schmiedebergs Archives of Pharmacology. 352, 149-156.
  • Bames, N. IvI and Sharp, T., 1999, A review of central 5-HT receptors and their function. Neuropharmacology. 38, 1083.
  • Bartrup, J. T. and Newberry, N. R., 1996, Electrophysiological consequences of ligand binding to the desensitized 5-HTs receptor in mammalian NG106-15 cells. Journal of Physiology. 490, 679-690.
  • Bertrand, D., Galzi, J.-L, Devillers-Thiery, A., Bertrand, S. and Changeux, J.-P., 1993, Mutations at two distinct sites within the channel domain M2 alter calcium permeabiity of neuronal a7 nicotinic receptor. Proceedings of the National Academy of Sciences (USA). 90, 6971-6975.
  • Blanton, M P., MsCardy, E. A., Fryer, J. D., Liu, M H. and Lukas, R. J., 2000, 5-Hydroxylryptamne interaction with the nicotinic acetylchoine receptor. European Journal of Pharmacology. 389, 155.
  • Blasey, H. D., Brethon, B., Hovius, R., Vogel, H., Tari, A. P., Lundstrcm, K., Rey, L and Bernard, A. R., 2000, Large scale transient 5-HT3 receptor production with the Semliki forest virus expression system. Cytotechnology 32, 199-208.
  • Boess, F. G., Beroukhrn, R. and Martin, I. L., 1995, Ultrastructure of the 5-hydroxytryptamrie3 receptor. Journal of Neurochemistry, 64, 1401-1405.
  • Boess, F. G., Sepúlveda, M-I., Lummis, S. C. R. and Martin, I. L., 1992, 5-HT3 receptors ri NG103-15 neuroblastoma × glioma cells: effect of the novel agonist 1-(m-chlarophenyl)-biguanide. Neuropharmacology. 31, 561-564.
  • Boess, F. G., Steward, L. J., Steele, J. A., Liu, D., Reid, J., Glencorse, T. A. and Martin, I. L, 1997, Analysis of the ligand binding site of the 5-HTs receptor using site directed muta genesis: importance of glutamate 106. Neuropharmacology, 36, 637-647.
  • Borea, P. A., Dalpiaz, A., Varani, K., GiIIi, P. and GiIi, G., 2000, Can thermodynamic measurements of receptor binding yield riformation on drug affinity and efficacy? Biochemical Pharmacology. 60, 1549-1556.
  • Bouzat C. and Barrantes, F. J., 1997, Assigning functions to residues ri the acetylchoine receptor channel region (review). Molecular Membrane Biology. 14,167-177.
  • Bradley, P. B., Engel, G., Feniuk, W., Fozard, J. R., Humphrey, P. P., Middlemiss, D. N., Mylecharane, E. J., Richardson, B. P. and Saxena, P. R., 1986, Proposals for the classification and nomenclature of functional receptors for 5-hydroxylryptamine. Neurophamnacology, 25, 563-576.
  • Brady, C. A., Stanford, I. M, AIi, I. L L, Wiliams, J. M, Dubin, A. E., Hope, A. G. and Barnes, N. M., 2001, Pharmacobgeal comparison of human homomeric 5-HT3A receptors versus heteromeric 5-HTsA/ receptors. Neuropharmacology. 41, 282.
  • Breitinger, H. G. A., Wieboldt, R., Ramesh D., Carpenter, B. K. and Hess, G. P., 2000, Synthesis and characterization of photolabile derivatives of serotonin for chemical kinetic investigations of the serotonin 5-HT3 receptor. Biochemistry, 39, 5500-5508.
  • Brejc, K., van DiJc, W. J., Klaassen, R. V., Schuumans, M, van Der Oost J., Smit, A. B. and Sixma, T. K., 2001, Crystal structure of an ACh-binding protein reveals the ligand-binding domain of nicotinic receptors. Mature, 411, 269-276.
  • Brown, A. M, Hope, A. G., Lambert J. J. and Peters, J. A., 1998, Ion permeation and conduction ri a human recombinant 5-HT3 receptor subunit (HB-HT3A). Journal of Physiology. 507, 653-665.
  • Bruss, M, Barann, M, Hayer-Zillgen, M, Eucker, T., Gothert M and Bonisch, H., 2000, Modified 5-HT3A receptor function by coexpression of alternatively spliced human 5-HT3A receptor isoforms. Naunyn Schmiedebergs Archives of Pharmacology. 362, 392-401.
  • Bullock, A. E., Clark, A. L, Grady, S. R., Robrson, S. F., Slobe, B. S., Marks, M J. and Colins, A. C., 1997, Neurosteroids modulate nicotinic receptor function in mouse striatal and thalamic synaptosomes. Journal of Neurochemistry, 68, 2412-2423.
  • Bureau, R., Daveu, C., Bagln, I., Santas, J. S. D., Lancelot, J. C. and Rault, S., 2001, Association of two 3D QSAR analyses. Application to the study of partial agonist serotonin-3 ligands. Journal of Chemical Information and Computer Sciences. 41, 815- 823.
  • Changeux, J. P., Bessis, A., Bourgeois, J. P., Corringer, P. J., Devillers Thiery, A., Eisele, J. L., Kerszberg, M, Lena, C., LeNovere, N., Picciootto, M and Zoi, M, 1996, Niccitinic receptors and brain plasticity. Cold Spring Harbor Symposia On Quantitative Biology. 61, 343.
  • Cohen, B. N., Labarca, C., Czyzyk, L, Davidson, N. and Lester, H. A., 1992, TrJs4VNa+ permeability ratios of nicotinic acelylchoIre receptors are reduced by mutations near the intracellular end of the M2 region. Journal of General Physiology, 99, 545-572.
  • Corringer, P.-J., Bertrand, S., Gabi, J.-L, Devillers-Thiery, A., Changeux, J.-P. and Bertrand, D., 1999, Mutational analysis of the charge selectivity filter of the alpha-7 nicotinic acelylchoine receptor. Neuron. 22, 831-843.
  • Corriger, P.-J., Le Novere, N. and Changeux, J. P., 2000, Nicotinic receptors at the amino acid level. Annual Reviews of Pharmacology and Toxicology, 40, 431- 458.
  • Coultrap, S. J., Sun, H. W., Tenner, T. E. and Machu, T. K., 1999, Competitive antagonism of the mouse 5-hydroxylryptarnrie(3) receptor by bisrdotytmalernide I, a 'selective' protein kinase C inhibitor. Journal of Pharmacology and Experimental Therapeutics, 290, 76-82.
  • Cruz, H., Arrabit, C. and Slesinger, P., 2001, Structural features of the pore lining M2 transmembrane segment of the serotonin-gated ion channel. Biophysical Journal, 80, 336A.
  • Dang, H., England, P. M., Farivar, S. S., Dougherty, D. A. and Lester, H. A., 2000, Probing the role of a conserved Ml proline residue in 5-hydrcKylryptamine(3) receptor gating. Molecular Pharmacology. 57, 1114-1122.
  • Davies, P. A., Pistis, M, Hanna, M C., Peters, J. A., Lambert J. J., Hales, T. G. and Kirkness, E. F., 1999, The 5-HT3B subunit is a major determinant of serotonin-receptor function. Nature, 397, 359-363.
  • Deane, C. M and Lummis, S. C. R., 2001, The role and predicted propensity of prolre residues in the 5-HTs receptor. Journal of Biological Chemistry, 276, 37962-37966.
  • Derkach, V., Surprenant A. and North, R. A., 1989, 5-HT3 receptors are membrane ion channels. Nature, 339, 706-709.
  • Downie, D. L, Hope, A. G., Lambert J. J. Peters, J. A., Blackburn, T. P. and Jones, B. J., 1994, Pharmacological characterization of the apparent splice variants of the murine 5-HT3R-A submit expressed in Xenopus laevis oocytes. Neuropharmacology, 33, 473-482.
  • Doyle, D. A., Morais Cabrai, J., Pfuetzner, R. A., KUO, A., Gute, J. M, Cohen, S. L., Chait, B. T. and MacKinnon, R., 1998, The structure of the potassium channel: molecular basis of K+ conduction and selectivity. Science, 280, 69-77.
  • Dubin, A. E., Huvar, R., Dandrea. M R., Pyati, J., Zhu, J. Y., Joy, K. C., Wilson, S. J., Galrdo, J. E., Glass, C. A., Luo, L, Jackson, M R., Lovenberg, T. W. and Erlander, M G., 1999, The pharmacological and functional characteristics of the serotonin 5-HT3A receptor are specifically modified by a 5-HT3B receptor subunit Journal of Biological Chemistry, 274, 30799- 30810.
  • Edelster, S. J. and Changeux, J. P., 1998, Allosteric transitions of the acelylchoine receptor. Advances in Protein Chemistry, 51, 121-184.
  • Efeelé, J.-L, Bertrand, S., Galzi, J.-L., Devillers-Thiéry, A., Changeux, J.-P. and Bertrand, D., 1993, Chimaeric nicotinic-seratonergic receptor cambres distinct ligand binding and channel specificities. Nature, 366, 479-483.
  • England, P. M, Zhang, Y., Dougherty, D. A. and Lester, H. A., 1999, Backbone mutations in transmembrane domains of a ligand-gated ion channel: implications for the mechanism of gating. Cell, 96, 89-98.
  • Fan, P., Visentin, S. and Weight F. F., 1994, Effects of coca re on the serotonin-induced inward current in rat nodose ganglion neurons. Journal of Pharmacology and Experimental Therapeutics, 271, 262-266.
  • Filatov, G. M and White, M M, 1995, The role of conserved leucines in the M2 domain of the acelylchoine receptor in channel gating. Molecular Pharmacology, 48, 379-384.
  • Fletcher, S., Lindstrom, J. M, McKernan, R. M and Barnes, N. M, 1998, Evidence that porcine native 5-HT3 receptors do not contain nicotinic acetylcholine receptor subunits. Neuropharmacology, 37, 397-399.
  • Forman, S. A., Miller, K. W. and Yellen, G., 1995, A discrete site fagenera I anesthetics on a postsynaptic receptor. Molecular Pharmacology, 48, 574-581.
  • Franks, N. P. and Lieb, W. R., 1994, Molecular and cellular mechanisms of general anesthesia. Nature, 367, 607-613.
  • Gaddum, J. H. and Picareli, Z. P., 1957, Two kinds of tryptarrine receptor. British Journal of Pharmacology, 12, 323-328.
  • Galzi, J.-L. and Changeux, J.-P., 1994, Neurptransrritter-gated ion channels as unconventional allosteric praters. Current Opinion in Structural Biology, 4, 554-565.
  • Galzi, J.-L. and Changeux, J. P., 1995, Neuronal nicotinic receptors: molecular organization and regulations. Neuropharmacology. 34, 563-582.
  • Galzi, J.-L, Bertrand, S., Corringer, P. J., Changeux, J. P. and Bertrand, D., 1996, Identification of calcium binding sites that regulate potentiation of a neuronal nicotinic acetylcholine receptor. EMBO Journal, 15, 5824-5832.
  • Galzi, J.-L, Devillers-Thièry, A., Hussy, N., Bertrand, S., Changeux, J.-P. and Bertrand, D., 1992, Mutations r the channel domain of a neuronal nicotinic receptor convert ion selectivity from cationic to anionic. Nature, 359, 500-505.
  • Gill, C. H., Peters, J. A. and Lambert J. J., 1995, An electrophysiological investigation of the properties of a murine recombinant 5-HTs receptor stably expressed r HEK 293 cells. British Journal cf Pharmacology. 114, 1211-1221.
  • Gilon, P. and Yakel, J. L., 1995, Activation of 5-HT3 receptors expressed r Xenopus oocytes does not increase cytoplasmic Ca2+ levels. Receptors & Channels. 3, 83-88.
  • Glitsch, M, Wischmeyer, E. and Karschin, A., 1996, Functional characterization of two 5-HT3 receptor splice variants isolated from a mouse hippocampal cell line. Pflugers Archives. 432,134143.
  • Göme-Tschelnokow, U., Strecker, A., Kaduk, C., Naumann, D. and Hucho, F., 1994, The transmembrane domains of the nicotinic acetybhoine receptor contain a-helical and a structures. EMBO Journal. 13, 338-341.
  • Gready, J. E., Ranganathan, S., Schofield, P. R., Matsuo, Y. and Nishkawa, K., 1997, Predicted structure of the extracellular region of ligand-gated ion-channel receptors shows SH2-like and SH3like domains forming the ligand-binding site. Protein Science. 6, 983-998.
  • Green, T., Stauffer, K. A. and Lummis, S. C., 1995, Expression of recombinant homo-oigcmenc 5-hydpoxytryptamres receptors provides new insights into their maturation and structure. Journal of Biological Chemistry. 270, 6056-6061.
  • Greenshaw, A. J. and Silver-stone, P. H., 1997, The non-antiemetic uses of serotonin 5-HTs receptor antagonists. Clinical pharmacology and therapeutic applications. Drugs, 53, 20-39.
  • Grosman, C., Zhou, M and Auerbach, A., 2000, Mapping the conformational wave of acetylcholine receptor channel gating. Nature, 403, 773-776.
  • Grutter, T. and Changeux, J.-P., 2001, Nicotinic receptors in wonderland. Trends in Biochemical Sciences. 26, 459.
  • Gunthorpe, M J. and Lummis, S. C., 1999, Diltiazem causes open channel block of recombinant 5-HT3 receptors. Journal of Physiology. 519, 713-722.
  • Gunthorpe, M J. and Lummis, S. C. R., 2001, Conversion of the ion selectivity of the 5-HT3A receptor from cationic to anionic reveals a conserved feature of the ligand-gated ion channel superfamily. Journal of Biological Chemistry, 276, 10977-10983.
  • Gurrthorpe, M J., Peters, J. A., Gill, C. H., Lambert, J. J. and Lumrnis, S. C., 2000, The 4'lysine r the putative channel lining domain affects desensitization but not the single-channel conductance of recombinant homomeric 5-HT3A receptors. Journal of Physiology. 522, 187-198.
  • Gurley, D. A. and Lanthorn, T. H., 1998, Nicotinic agonists competitively antagonize serotonin at mouse 5-HT3 receptors expressed r Xenopus oocytes. Neuroscience Leiters. 247, 107.
  • Hanna, M C., Davies, P. A., Hales, T. G. and Kirkness, E. F., 2000, Evidence for expression of heteromeric serotonin 5-HT3 receptors in rodents. Journal of Neurochemistry. 75, 240-247.
  • Hargreaves, A. C., Gurrthorpe, M J., Taylor, C. W. and Lummis, S. C. R., 1996, Direct inhibition of 5-hydroxytryptamine3 receptors by antagonists of L-type Ca2+ channels. Molecular Pharmacology. 50, 1284-1294.
  • Hargreaves, A. C., Lummis, S. C. and Taylor, C. W., 1994, Ca2+ permeability of cloned and native 5-hydroxytryptamrie type 3 receptors. Molecular Pharmacology. 46, 1120-1128.
  • Harkness, P. C. and Millar, N. S., 2001, Inefficient cell-surface expression of hybrid complexes formed by the co-assembly of neuronal nicotinic acetylchoine receptor and seratonin receptor subunits. Neuropharmacology, 41, 79-87.
  • Hope, A. G., BeIeIIi, D., Mair, I. D., Lambert. J. J. and Peters, J. A., 1999, Molecular determinants of (+)tubocurarine binding at recombinant 5-hydroxylryptamrie3A receptor subunits. Molecular Pharmacology, 55, 1037-1043.
  • Hope, A. G., Downie, D. L, Sutherland, L, Lambert J. J., Peters, J. A. and Burchell, B., 1993, Cloning and functional expression of an apparent splice variant of the murine 5-HTa receptor A subunit European Journal of Pharmacology, 245, 187-192.
  • Horensten, J., Wagner, D., Czajkowski, C. and Akabas, M, 2001, Protein mobility and GABA-induced conformational changes in GABA(A) receptor pore-lining M2 segment Nature Neuroscience, 4, 477-485.
  • Hoyer, D. and Martin, G., 1997, 5-HT receptor classification and nomenclalure: towards a harmonization with the human genome. Neuropharmacology, 36, 419-428.
  • Hoyer, D. and Neijt, H. C., 1988, Identification of serotonin 5-HT3 recognition sites in membranes of N1E-115 neuroblastoma cells by radioligand binding. Molecular Pharmacology. 33, 303- 309.
  • Hubbard, P. C. and Lummis, S. C. R., 2000, Zn2+ enhancement of the recombinant 5-HT3 receptor is modulated by divalent cations. European Journal of Pharmacology. 394, 189-197.
  • Humphrey, P. P., Bountra, C., Clayton, N. and Kozlowski, K., 1999, Review article: the therapeutic potential of 5-HT3 receptor antagonists in the treatment of irritable bowel syndrome. Aliment Pharmacological Therapy, 13 (Suppl 2), 31-38.
  • Imoto, K., Busch, C., Sakmann, B., Mishina, M, Konno, T., Nakai, J., Bujo, H., Mori, Y., Fukuda, K. and Numa, S., 1988, Rings of negatively charged amino acids determine the acetylcholine receptor channel conductance. Nature, 335, 645-648.
  • Jackson, M B. and Yakel, J. L, 1995, The 5-HT3 receptor channel. Annual Reviews in Physiology. 57, 447-468.
  • Jenkins, A., Franks, N. P. and Lieb, W. R., 1996, Actions of general anaesthetics on 5-HT3 receptors in N1E-115 neuroblastoma cells. British Journal of Pharmacology. 117, 1507-1515.
  • Johnson, D. S. and Heinemann, S. F., 1992, Cloning and expression of the rat 5-HT3 receptor reveals species-specific sensitivity to curare antagonism. Society for Neuroscience Abstracts. 18, 249.
  • Jones, S. and Yakel, J. L., 1998, Ca2+ influx through voltage-gated Ca2+ channels regulates 5-HT3 receptor channel desensitisation ri rat glioma × mouse neuroblastoma hybrid NG108-15 cells. Journal of Physiology. 510, 361- 370.
  • Karlin, A. and Akabas, M H., 1995, Toward a structural basis for the function of nicotinic acelylchoine receptors and their cousins. Neuron, 15, 1231-1244.
  • Keramidas, A., Moorhouse, A. J., French, C. R., Schofield, P. R. and Barry, P. H., 2000, M2 pore mutations con vert the glycine receptor channel from being anion- to cation-selective. Biophysical Journal, 79, 247-259.
  • Khakh, B. S. and Lester, H. A, 1999, Dynamic selectivity filters in ion channels. Neuron, 23, 653-658.
  • Kienker, P., Tomaselli, G., Juman, M and Yellen, G., 1994, Conductance mutations of the nicotinic acetylchoine receptor do not act by a simple electrostatic mechanism. Biophysical Journal, 66, 325-334.
  • Kooyman, A. R., van Hooft, J. A. and Vijverberg, H. P., 1993a, 5Hydroxyrdole slows desensrtization of the 5-HT3 receptormediated ion current in N1E-115 neuroblastama cells. British Journal of Pharmacology. 108, 287-289.
  • Kooyman, A. R., Zwart R. and Vijverberg, H. P., 1993b, Tetraethylammonium ions block 5-HT3 receptor-mediated ion current at the agonist recognition site and prevent desensrtization in cultured mouse neuroblastama cells. European Journal of Pharmacology. 246 247-254
  • Kosolapov, A V., Filatov, G. N. and White, M M, 2000, Acetylcholine receptor gating is influenced by the polarity of amino acids at position 9' in the M2 domain. Journal of Membrane Biology. 174, 191.
  • Kriegler, S., Sudweeks, S. and Yakel, J. L, 1999, The nicotinic a4 receptor subunit contributes to the lining of the ion channel pore when expressed with the 5-HTs receptor subunit Journal of Biological Chemistry, 274, 3934- 3936.
  • Labarca, C., Nowak, M W., Zhang, K, Tang, L, Deshpande, P. and Lester, H. A., 1995, Channel gating governed symmetrically by conserved leucine residues in the M2 domain of nicotinic receptors. Nature, 376, 514-516.
  • Lambert J. J., Peters, J. A., Hales, T. G. and Dempster, J., 1989, The properties of 5-HTs receptors ri clonal cell lines studied by patch- clamp techniques. British Journal of Pharmacology, 97, 27-40.
  • Lankiewicz, S., Huser, M B., Heumann, R., Halt, H. and Gissemann, G., 2000, Phosphorylation of the 5-hydroxytryptamine3 (5-HTs) receptor expressed ri HEK293 cells. Receptors & Channels. 7, 9-15.
  • Lankiewicz, S., Lobitz, N., Wetzel, C. H. R., Rupprecht R., Gissemann, G. and Halt, K, 1998, Molecular cloning, functional expression, and pharmacologcal characterization of 5-hydroxytryptamine3 receptor cDNA and its splice variants from guinea pig. Molecular Pharmacology, 53, 202-212.
  • Le Novere, N. and Changeux, J.-P., 1995, Molecular evolution of the nicotinic acetyfcholine-receptor- an example of multigene family in excitable cells. Journal of Molecular Evolution. 40, 155.
  • Le Novere, N. and Changeux, J.-P., 2001, LGICdb: the ligand-gated ion channel database. Nucleic Acids Research, 29, 294.
  • Leite, J. F. and Cascio, M, 2001, Structure of ligand-gated ion channels: critical assessment of biochemical data supports novel topology. Molecular and Cellular Neuroscience, 17, 777-792.
  • Leite, J. F., Amoscato, A. A. and Cascio, M, 2000, Coupled proteolytic and mass spectrometry studies indicate a novel topology for the glycine receptor. Journal of Biological Chemistry, 275, 13683-13689.
  • Lobitz, N., Gissemann, G., Hatt, H. and Wetzel, C. H., 2001, A single amino-acid in the TM1 domain is an important determinant of the desensitizalion kinetics of recombinant human and guinea pig albha-homomeric 5-hydroxytryptamine type 3 receptors. Molecular Pharmacology, 59, 844- 851.
  • Lovinger, D. M., 1991, lnhbition of 5-HT3 receptor-mediated ion current by divalent metal cations ri NCB-20 neuroblastoma cells. Journal of Neurophysiology, 66, 1329-1337.
  • Lovinger, D. M, 1999, 5-HT3 receptors and Hie neural actions of alcohols: an increasrigry exciting tope. Neurochemislry International. 35, 125-130.
  • Lummis, S. C. R. and Baker, J., 1997, Radioligand binding and photoaffinity labelling studies show a direct interaction of phenothiazries at 5-HT3 receptors. Neuropharmacology. 36, 665-670.
  • Lynch, J. W., Man, N. I. and Schofield, P. R., 1999, Building new function into glycine receptors : a structura I model for the activation of the glycine-gated chloride channel. Clinical and Experimental Physiology and Pharmacology, 26, 932-934.
  • Lynch, J. W., Rajendra, S., Pierce, K. D., Handford, C. A., Barry, P. H. and Schofield, P. R., 1997, Identification of intracellular and extracellular domains mediating signal transduction ri the inhibitory glycine receptor chloride channel. EMBO Journal, 16, 110-120.
  • Macdonald, R. L. and Oben, R. W., 1994, GABAA receptor channels. Annual Reviews in Neuroscience, 17, 569-602.
  • Machu, T. K. and Harris, R. A., 1994, Alcohols and anesthetics enhance the function of B-hydroxytryptamine3 receptors expressed in Xenopus laevis oocytes. Journal of Pharmacology and Expertnental Therapeutics, 271, 898-905.
  • Maksay, G., 1998, Bidrectional allosteric modulation of strychninesensitive glycine receptors by tropeines and 5-HT3 seroton in receptor ligands. Neuropharmacology, 37, 1633.
  • Melone, H. M, Peters, J. A and Lambert J. J., 1991, Physiological and pharmecologcal properties of 5-HT3 receptors- a patchclamp study. Neuropeptides, 19, 25-30.
  • Maricq, A V., Peterson, A S., Brake, A J., Myers, R. M and Julius, D., 1991, Primary structure and functional expression of the 5HT3 receptor, a serotonin-gated ion channel. Science, 254, 432-437.
  • McCooL B. A. and Lovinger, D. M, 1995, lfenprodil inhbition of the 5-hydroxytryptamrie3 receptor. Neurophannacology, 34, 621629.
  • McKeman, R., 1992, Biochemical properties of the 5-HT3 receptor. In Cental and Peripheral 5-HT3 receptors, M Hamon, ed. (London: Academic Press), 89-102.
  • Menziani, M C., De Rienzo, F., Cappelli, A., Anzini, M and De Benedetti, P. G., 2001, A computational model of the 5-HT3 receptor extracellular domain: search for ligand binding sites. Theoretical Chemistry Accounts, 106, 98-104.
  • Methot N., Ritehie, B. D., Blanton, M P. and Baenziger, J. E., 2001, Structure of the pore-farming transmembrane domain of a ligandgated ion channel. Journal of Biological Chemistry, 276, 2372623732.
  • Mihic, S. J., Ye, Q., Wick. M J., Koltchine, V. V., Krasowski, M D., Finn, S. E., Mascia, M P., Valenzueb, C. F., Hanson, K. K., Greenblatt, E. P., Harris, R. A. and Harrison, N. L, 1997, Sites of alcohol and volatile anaesthetic action on GABA(A) and glycine receptors. Nature, 389, 385-389.
  • Miquel, M C., Emerit M B., Gingrich, J. A., Nosjean, A., Hamon, M. and el Mestikawy, S., 1995, Developmental changes in the differential expression of two serotonin 5-HT3 receptor splice variants in the rat. Journal of Neurochemistry, 65, 475-483.
  • Myake, A., Machizuki, S., Takemoto, Y. and Akuzawa, S., 1995, Molecular clonrig of human 5-hydroxytryptamine3 receptor: heterogeneity in distrbution and function among species. Molecular Pharmacology, 48, 407-416.
  • Myazave, A., Fujyoshi, Y., Stowell, M and Unwin, N., 1999, Nicotinic acetylcholine receptor at 4.6 A resolution: transverse tunnels in the channel wall. Journal of Molecular Biology. 288, 765-786.
  • Machizuki, S., Myake, A. and Furuchi, K., 1999a, Identification of a domari affecting agonist potency of meta-chlcrophenylbiguanide in 5-HT3 receptors. European Journal of Pharmacology, 369, 125-132.
  • Machizuki, S., Myake, A. and Furuichi, K., 1999b, Ion permeation properties of a cloned human 5-HT3 receptor transiently expressed in HEK 293 cells. Amino Acids, 17, 243-255.
  • Machizuki, S., Watanabe, T., Myake, A., Saito, M and Furuichi, K., 2000, Cloning, expression, and characterization of ferret 5-HT3 receptor submit European Journal of Pharmacology, 399, 97106.
  • Morales, M, Kirkness. E., MeCollum, N. and MeCullough, K., 2000. Co-expression of the 5-HT3 receptor subunits A and B in the dorsal root ganglion. Society for Neuroscience Abstracts, 811.1.
  • Mott D., Erreger, K., Banke, T. and Traynelis, S., 2001, Open probability of homomeric murine 5-HT3A serotonin receptors depends on subunit occupancy. Journal of Physiology, 535, 427-443.
  • Mukerji, J., Haghighi, A. and Seguela, P., 1996, Immunological characterization and transmembrane topology of 5-hydroxylryptamine3 receptors by functional epitope taggrig. Journal of Neurochemistry, 66, 1027-1032.
  • Nayak, S. V., Ronde, P., Spier, A. D., Lummis, S. C. R. and Nichols, R. A., 1999, Calcium changes induced by presynaptic 5hydroxylryplamine-3 serotonin receptors on isolated termrials from various regions of the rat brain. Neuroscience, 91, 107-117.
  • Neijt, H. C., te Duits, I. J. and Vijverberg, H. P., 1988, Pharmacological characterization of serotonin 5-HT3 receptor-mediated electrical response in cultured mouse neuroblastoma cells. Neuropharmacology, 27, 301 -307.
  • Nichols, R. A. and Mallard, P., 1996, Direct observation of serotonin 5-HT3 receptor-induced increases in calcium levels in individual brain nerve termrials. Journal of Neurochemistry. 67, 581-592.
  • Niemeyer, M-I. and Lummis, S. C. R., 1998, Different efficacy of specific agonists at 5-HT3 receptor splice variants: the role of the extra six amino acid segment British Journal of Pharmacology, 123, 661-666.
  • Niemeyer, M-I. and Lummis, S. C. R., 2001, The role of the agonist binding site in Ca2+ inhibition of the recombinant 5-HT3A receptor. European Journal of Pharmacology, 428, 153-161.
  • North, R. A., 1995, Ligand- and voltage-gated ion channels. In Handbook of receptors and channels. S. Peroutka, eds (Boca Raton: CRC Press), 1 -349.
  • Nutter, T. J. and Adams, D. J., 1995, Monovalent and divalent-cation permeability and block of neuronal nicotinic receptor channels in rat parasympathetic gangia. Journal of General Physiology. 105, 701-723.
  • Orteils, M O. and Lunt G. G., 1995, Evolutionary history of the ligand-gated ion-channel superfamily of receptors. Trends in Neurosciences. 18, 121-127.
  • Parker, R. M, Bentley, K. R. and Barnes, N. M, 1996, Allosteric modulation of 5-HT3 receptors: focus on alcohols and anaesthetic agents. Trends in Pharmacological Sciences, 17, 95-99.
  • Pascual, J. M and Karin, A., 1998, State-dependent accessibility and electrostatic potential ri the channel of the acetylcholine receptor. Inferences from rates of reaction of thiosulfonates with substituted cysteines in the M2 segment of the alpha subunit. Journal of General Physiology, 111, 717-739.
  • Pashkov, V. S., Mastennikov, I. V., Tchikin, L D., Efremov, R. G., Ivancv, V. T. and Arseniev, A. S., 1999, Spatial structure of the M2 transmembrane segment of the nicotinic acetylchoine receptor alpha-subunit FEBS Letters, 457, 117.
  • Peters, J. A., Hales, T. G. and Lambert J. J., 1988, Diva lent cations modulate 5-HTs receptor-induced currents in N1E-115 neuroblatoma cells. European Journal of Pharmacology. 151, 491-495.
  • Peters, J. A., Hope, A. G., Sutherland, L and Lambert, J. J., 1997, Recombinant 5-hydroxytryptamines receptors. In Recombinant Cell Surface Receptors: Focal Pont for Therapeutic Intervention. M. J. Bronne, eds (R.G.Landes Co.), 119-153.
  • Peters, J. A., Malone, H. M and Lambert, J. J., 1992, Recent advances n the electrophysiological characterization of 5-HT3 receptors. Trends in Pharmacological Sciences, 13, 391-397.
  • Pootanakit, K. and Brunken, W. J., 2001, Identification of 5-HT3A and 5-HT3 Breceptor subunits inmarrrnalianretinae: potentialpre-synaptic modulators of photoreceptors. Brain Research, 896, 77- 85.
  • Price, K. and Lummis, S. C. R., 2001, The role of conserved tyrosine residues r the binding site of 5-HTs receptors. British Journal of Pharmacology. 134,143P.
  • Quirk, P. and Siegel, R., 2000, N-Glycosylation is necessary for surface expression of the 5-HTs receptor. Society for Neuroscience Abstracts, 811.4.
  • Rajendra, S., Lynch, J. W., Pierce, K. D., French, C. R., Barry, P. H. and Schofield, P. R., 1994, Startle disease mutations reduce the agonist sensitivity of the human inhbitory glycine receptor. Journal of Biological Chemistry, 269, 18739-18742.
  • Ranganathan, R., Cannon, S. C. and Horvitz, H. R., 2000, MOD-1 is a serotonin-gated chloride channel that modulates locomotory behaviour n C. elegans. Nature, 408, 470.
  • Rapport, M M, 1949, Seam vasoconstrictor (Serotonin) V. The presence of creatinrie in the complex. A proposed structure of the vasoconstrictor priciple. Journal of Biological Chemistry, 180, 961-969.
  • Rapport, M M, Green, A. A. and Page, I. H., 1947, Purification of the substance which is responsible for vasoconstrictor activity of serum. Federal Proceedings, 6, 184.
  • Rapport, M M, Green, A A. and Page, I. H., 1948a, Seam vasoconstrictor (Serotonin) IV. Isolation and characterization. Journal of Biological Chemistry, 176, 1243-1251.
  • Rapport, M M, Green, A. A. and Page, I. H., 1948b, Partial purification of the vasoconstrictor ri beef serum. Journal of Biological Chemistry, 174, 735-741.
  • Rapport, M M, Green, A. A. and Page, I. H., 1948c, Serum vasoconstrictor (Serotonin) III. Chemical inactivation. Journal of Biological Chemistry, 176, 1237-1241.
  • Rapport M M, Green, A. A. and Page, I. H., 1948d, Crystaline serotonin. Science, 108, 329-330.
  • Reeves, D. C. and Lummis, S. C. R., 2000, Mutation of an isoleucine residue M2 alters the Ca2+ permeabiity of 5-HT3A receptors. British Journal of Pharmacology. 129, 39P.
  • Reeves, D. C., Goren, E. N., Akabas, M H. and Lummis, S. C. R., 2001, Structural and electrostatic properties of the 5-HTs receptor pore revealed by substituted cysteine accessibility mutagenesis. Journal of Biological Chemistry. 276, 42035-42042
  • Revah, F., Beilrand, D., Gabi, J.-L, Devillers-Thiéry, A., Mulle, C., Hussy, N., Bertrand, S., Ballivet, M and Changeux, J.-P., 1991, Mutations in the channel domain alter desensitization of a neuronal nicotinic receptor. Natre, 353, 846-849.
  • Revah, F., Gabi, J.-L, Graudat, J., Haumont P. Y., Lederer, F. and Changeux, J.-P., 1990, The noncampetitive blocker [3H]chlorpromazine labels three amino acids of the acetyfchoine receptor asubunit implications for the a-helical organization of regions Ml and for the structure of the ion channel. Proceedings of the National Academy of Sciences (USA). 87, 4675-4679.
  • Rizzi, J. P., Nagel, A. A., Rosen, T., McLean, S. and Seeger, T., 1990, An initiaI three-component pharmacophore for specific serotonin-3 receptor ligands. JournaI of Medicinal Chemistry, 33, 2721-2725.
  • Robertson, B. and Bevan, S., 1991, Properties of 5-hydroxytryptemine3 receptor-gated currents in adult-rat dorsal-root ganglion neurons. British Journal of Pharmacology. 102, 272-276.
  • Rondé, P. and Nichols, R. A., 1997, 5-HT3 receptors induce rises in cytosolic and nuclear calcium in NG106-15 cells via calciuminduced calcium release. Cell Calcium. 22, 357-365.
  • Schmieden, V., Kuhse, J. and Betz, H., 1993, Mutation of glycine receptor subunit creates beta-abnne receptor responsive to GABA. Science, 262, 256-258.
  • Sepulveda, M I., Baker, J. and Lummis, S. C., 1994, Chlorpromazine and OX222 block 5-HT3 receptors in N1E-115 neuroblastoma cells. Neuropharmacology, 33, 493- 499.
  • Sivilatti, L. and Colquhoun, D., 1995, Acetylcholine-receptors- too many channels, too few functions. Science. 269, 1681.
  • Spier, A. D. and Lummis, S. C., 2000, The role of tryptophan residues in the 5-Hydroxylryptamine(3) receptor ligand binding domain. Journal of Biological Chemistry, 275, 5620-5625.
  • Spier, A. D., Wotherspcon, G., Nayak, S. V., Nichols, R. A., Priestley, J. V. and Lummis, S. C. R., 1999, Antibodies against the extracellular domain of the 5-HT3 receptor label both native and recombinant receptors (vol 67, pg 221, 1999). Molecular Brain Research. 71, 369.
  • Steward, L J., Boess, F. G., Steele, J. A, Liu, D., Wang, N. and Martin, I. L., 2000, Importance of phenylalanine 107 in agonist recognition by the 5-hydroxylryptamne(3A) receptor. Molecular Pharmacology. 57,1249-1255.
  • Steward, L J., Boess, F. G., Steele, J. A, Phipps, B. P., Liu, D. and Martin, I. L, 1996, The importance of the amino acid phenylalanine 107 for function and ligand recognition at the 5-HT3 receptor. British Journal of Pharmacology. 119, 290P.
  • Sun, H. W. and Machu, T. K., 2000, Bicuculine antagonizes 5-HT3A and alpha 2 glycine receptors expressed in Xenopus oocytes. European Journal of Pharmacology. 391, 243.
  • Sung, K., Engel, S. R., Allan, A. M and Lovinger, D. M, 2000, 5HT(3) receptor function and potentiation by alcohols in frontal cortex neurons from transgenic mice overexpressing the receptor. Neuropharmacology. 39, 2346-2351.
  • Suprenant A. and Crist, J., 1988, Electrophysiological characterization of functionally distinct 5-hydroxytryptamine receptors on guinea-pig submucous plexus. Neuroscience, 24, 283-295.
  • Takenouchi, T. and Munekata, E., 1998, Serotonin increases cytoplasmic Ca2+ concentration in PC12 cells: effect of tachykinin peptides. Neuroscience Letters. 246, 141-144.
  • Taylor, C. W. and Broad, L M, 1998, Pharmacologeal analysis of intracelluar Ca2+ signaling: problems and pitfalls. Trends in Pharmacological Sciences. 19, 370-375.
  • Tikhonov, D. B. and Zhorov, B. S., 1998, Kinked-helices model of the nicotinic acetylcholine receptor ion channel and its complexes with blockers: simulation by the Monte Carlo minimization method. Biophysical Journal, 74, 242-255.
  • Tsunoyama, K. and Gojobori, T., 1998, Evolution of nicotinic acetybhoine receptor subunits. Molecular Biology and Evolution. 15, 518.
  • Tyers, M B., Bunce, K. T. and Humphrey, P. P., 1989, Pharmacological and anti-emetic properties of ondansefron. European Journal of Cancer and ClinicaI Oncology. 25, S15-S19.
  • Uetz, P., Abdebtly, F., Villarroel, A, Rappold, G., Weiss, B. and Koenen, M, 1994, Organisation of the murine 5-HT3 receptor gene and assignment to human chromosome 11. FEBS Leiters, 339, 302-306.
  • Unwin, N., 1993, Nicotinic acelylchoine receptor at 9 A resolution. Journal of Molecular Biology. 229, 1101 -1124.
  • Unwin, N., 1995, Acetylcholrie receptor channel imaged in the open state. Nature, 373, 37-43.
  • Unwin, N., 1996, Projection structure of the nicotinic acetylcholine receptor distinct conformations of the alpha subunits. Journal of Molecular Biology, 257, 586-596.
  • Unwin, N., 1998, The nicotinic acetylcholine receptor of the Torpedo electric ray. Journal of Stuctural Biology. 121, 181-190.
  • Unwin, N., 2000a, Nicotinic acetylcholine receptor: structure and mechanism. Journal of General Physiology, 116, 5.
  • Unwin, N., 2000b, The Croonian Lecture 2000. Nicotinic acetylcholine receptor and the structural basis of fast synaptic transmission. Philosophical Transactions of the Royal Society of London Series B- Biological Sciences. 355, 1813.
  • Valera, S., Balivet, M. and Bertrand, D., 1992, Progesterone modulates a neuronal nicotinic acetylcholine-receptor. Proceedings of the National Academy of Sciences (USA). 89, 9949- 9953.
  • van Hooft, J. A. and Vijverberg, H. P., 1995, Phospharylation controls conductance of 5-HTs receptor ligand-gated ion channels. Receptors & Channels. 3, 7-12.
  • van Hooft, J. A. and Vijverberg, H. P. M. 2000, 5-HT3 receptors and neurotransmitter release in the CNS: a nerve ending story? Trends in Neurosciences, 23, 605-610.
  • van Hooft, J. A., Spier, A. D., Yakel, J. L, Lummis, S. C. and Vijverberg, H. P., 1998, Promiscuous coassembly of serotonin 5HT3 and nicotinic a4 receptor subunits into Ca(2+)-permeable ion channels. Proceedings of the National Academy of Sciences (USA). 95, 11456-11461.
  • van Hooft, J. A., van der Haar, E. and Vijverberg, H. P., 1997, Allosteric potentiation of the 5-HTs receptor-mediated ion current in N1E-115 neuroblastoma cells by 5-hydroxyindole and analogues. Neuropharmacology, 36, 649- 653.
  • Vandenberg, R. J., Handford, C. A. and Schofield, P. R., 1992, Distinct agonist- and antagonist-binding sites on the glycine receptor. Neuron, 9, 491- 496.
  • Wemer, P., Kawashrna, E., Reid, J., Hussy, N., Lundstrom, K., Buell, G., Humbert Y. and Jones, K. A., 1994, Organization of the mouse 5-HT3 receptor gene and functional expression of two splice variants. Molecular Brain Research. 26, 233- 241.
  • Wetzel, C. H., Hermann, B., Behl, C., Pestel, E., Rammes, G., Zieglgansberger, VV., Holsboer, F. and Rupprecht R., 1998, Functional antagonism of gonadal steroids at the 5-hydroxytryptamine type 3 receptor. Molecular Endocrinology. 12, 1441-1451.
  • Williams, D. B. and Akabas, IvI H., 1999, gamma-aminobutyric acid increases the water accessibility of M3 membrane-spanning segment residues ri gamma-aminobutyric acid type A receptors. Biophysical Journal. 77, 2563-2574.
  • Wilson, G. G. and Karlin, A., 1998, The location of the gate in the acetyfchoine receptor channel. Neuron, 20, 1269-1281.
  • Wu, F. S., Gibbs, T. T. and Farb, D. H., 1990, Inverse modulation of gamma-aminobutyric acid-induced and glycine-induced currents by progesterone. Molecular Pharmacology, 37, 597-602.
  • Xu, M and Akabas, M H., 1996, Identification of channel-lining residues in the M2 membrane-spannrig segment of the GABAA receptor a1 subunit Journal of General Physiology, 107, 195-205.
  • Yakel, J. L and Jackson, M B., 1988, 5-HT3 receptors mediate rapid responses in cultured hippocampus and a clonal cell Iine. Neuron, 1, 615-621.
  • Yakel, J. L., Lagruda, A., Adekron, J. P. and North, R. A., 1993, Single amino acid substitution affects desensitization of the 5- hydroxytryptamine type 3 receptor expressed in Xenopus oocytes. Proceedings of the National Academy of Sciences (USA). 90, 5030-5033
  • Yakel, J. L, Shao, X. M and Jackson, M B., 1990, The selectivity of the channel coupled to the 5-HT3 receptor. Brain Research. 533, 46-52.
  • Yakel, J. L, Shao, X. M and Jackson, M. B., 1991, Activation and desensitization of the 5-HT3 receptor in a rat glioma × mouse neuroblastoma hybrid cell. Journal of Physiology. 436, 293-308.
  • Yan, D., Pedersen, S. E. and White, M. M, 1998, Interaction of D-tubocurarine analogs with the 5HT3 receptor. Neuropharmacology. 37, 251-257.
  • Yang, J., 1990, Ion permeation through 5-hydroxytryptamrie-gated channels in neuroblastoma N18 cells. Journal of General Physiology. 96, 1177-1198.
  • Yang, J., Mathie, A. and HiIIe, B., 1992, 5-HT3 receptor channels in dissociated rat superior cervical gangion neurons. Journal of Physiology. 448, 237-256.
  • Ye, J. H., Hunt T., Wu, W.-H. and McArdle, J. J., 1997, Ondansetron modulates GABA(A) current of rat central nervous system neurons. European Journal of Pharmacology, 337, 87-94.
  • Zhang, L., OZ, M, Stewart, R. R., Peoples, R. W. and Weight F. F., 1997, Volatile general anaesthetic actions on recombinant nACh alpha 7, 5-HT3 and chimeric nACh alpha 7-5-HT3 receptors expressed in Xenopus oocytes. British Journal of Pharmacology, 120, 353-355.
  • Zhou Q., Verdoom, T. A. and Lovinger, D. M, 1998, Alcohols potentiate the function of 5-HT3 receptor-channels on NCB-20 neuroblastoma cells by favouring and stabilizing the open channel state. Journal of Physiology. 507, 335-352.

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