The Discovery of Multiple Serotonin Receptor Subtypes: A Lesson from Molecular Cloning to Functional Expression

  • Milt Teitler

The field of serotonin (5-HT) receptor pharmacology has been at least as dramatically altered by the advent of molecular neurobiology and recombinant DNA techniques, as has any other neurotransmitter receptor field. The principal reason for this is the unforeseen multitude of genes expressing different types of 5-HT receptors. Classical pharmacological studies as well as radioligand-binding studies convinced workers in the field that there were multiple 5-HT receptors. The extent of that multiplicity was not generally foreseen. Thirteen 5-HT receptor genes have been cloned and functionally expressed. All 13 receptors were cloned between the years 1987 and 1995. Adding to the complexity of 5-HT receptors pharmacology are the splice variants and, in one case, mRNA editing isoforms, detected in the last decade. Bringing order to this rapid outpouring of information at this time is a very difficult task. In order to provide a concise and timely review, this article focuses on the strategies used to clone and express multiple 5-HT receptors. Unique properties of the various receptors are emphasized.


Irritable Bowel Syndrome Adenylate Cyclase Xenopus Oocyte Serotonin Receptor Functional Expression 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.


Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.


  1. Adham N, Kao H T, Schecter L E, Bard J, Olsen M, Urquhart D, Durkin M, Hartig P R, Weinshank R L and Branchek T A (1993) Cloning of Another Human Serotonin Receptor (5-HT1F): A Fifth 5-HT1 Receptor Subtype Coupled to the Inhibition of Adenylate Cyclase. Proc Natl Acad Sci U S A 90: pp 408-412.CrossRefPubMedGoogle Scholar
  2. Adham N, Romanienko P, Hartig P, Weinshank R L and Branchek T (1992) The Rat 5-Hydroxytryptamine1B Receptor is the Species Homologue of the Human 5-Hydroxytryptamine1D Beta Receptor. Mol Pharmacol 41: pp 1-7.PubMedGoogle Scholar
  3. Amlaiky N, Ramboz S, Boschert U, Plassat J L and Hen R (1992) Isolation of a Mouse “5HT1E-Like” Serotonin Receptor Expressed Predominantly in Hippocampus. J Biol Chem 267: pp 19761-19764.PubMedGoogle Scholar
  4. Appel N M, Mitchell W M, Garlick R K, Glennon R A, Teitler M and De Souza E B (1990) Autoradiographic Characterization of (+-)-1-(2,5-Dimethoxy-4-[125I] Iodophenyl)-2-Aminopropane ([125I]DOI) Binding to 5-HT2 and 5-HT1c Receptors in Rat Brain. J Pharmacol Exp Ther 255: pp 843-857.PubMedGoogle Scholar
  5. Bai F, Yin T, Johnstone E M, Su C, Varga G, Little S P and Nelson D L (2004) Molecular Cloning and Pharmacological Characterization of the Guinea Pig 5-HT1E Receptor. Eur J Pharmacol 484: pp 127-139.CrossRefPubMedGoogle Scholar
  6. Bard J A, Zgombick J, Adham N, Vaysse P, Branchek T A and Weinshank R L (1993) Cloning of a Novel Human Serotonin Receptor (5-HT7) Positively Linked to Adenylate Cyclase. J Biol Chem 268: pp 23422-23426.PubMedGoogle Scholar
  7. Barnard E A (1988) Molecular Neurobiology. Separating Receptor Subtypes From Their Shadows. Nature 335: pp 301-302.CrossRefPubMedGoogle Scholar
  8. Battaglia G, Shannon M and Titeler M (1984) Guanyl Nucleotide and Divalent Cation Regula-tion of Cortical S2 Serotonin Receptors. J Neurochem 43: pp 1213-1219.CrossRefPubMedGoogle Scholar
  9. Bhalla P, Sharma H S, Wurch T, Pauwels P J and Saxena P R (2002) Molecular Cloning and Expression of the Porcine Trigeminal Ganglion CDNA Encoding a 5-Ht(1F) Receptor. Eur J Pharmacol 436: pp 23-33.CrossRefPubMedGoogle Scholar
  10. Blondel O, Gastineau M, Dahmoune Y, Langlois M and Fischmeister R (1998) Cloning, Expression, and Pharmacology of Four Human 5-Hydroxytryptamine 4 Receptor Isoforms Produced by Alternative Splicing in the Carboxyl Terminus. J Neurochem 70: pp 2252-2261.PubMedGoogle Scholar
  11. Bockaert J, Claeysen S, Compan V and Dumuis A (2004) 5-HT4 Receptors. Curr Drug Tar-gets CNS Neurol Disord 3: pp 39-51.CrossRefGoogle Scholar
  12. Bockaert J, Fozard J R, Dumuis A and Clarke D E (1992) The 5-HT4 Receptor: A Place in the Sun. Trends Pharmacol Sci 13: pp 141-145.CrossRefPubMedGoogle Scholar
  13. 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 Nomencla-ture of Functional Receptors for 5-Hydroxytryptamine. Neuropharmacology 25: pp 563-576.CrossRefPubMedGoogle Scholar
  14. Claeysen S, Faye P, Sebben M, Lemaire S, Bockaert J and Dumuis A (1997) Cloning and Expression of Human 5-HT4S Receptors. Effect of Receptor Density on Their Coupling to Adenylyl Cyclase. Neuroreport 8: pp 3189-3196.CrossRefPubMedGoogle Scholar
  15. Claeysen S, Faye P, Sebben M, Taviaux S, Bockaert J and Dumuis A (1998) 5-HT4 Recep-tors: Cloning and Expression of New Splice Variants. Ann N Y Acad Sci 861: pp 49-56.CrossRefPubMedGoogle Scholar
  16. Claeysen S, Sebben M, Journot L, Bockaert J and Dumuis A (1996) Cloning, Expression and Pharmacology of the Mouse 5-HT(4L) Receptor. FEBS Lett 398: pp 19-25.CrossRefPubMedGoogle Scholar
  17. Conductier G, Dusticier N, Lucas G, Cote F, Debonnel G, Daszuta A, Dumuis A, Nieoullon A, Hen R, Bockaert J and Compan V (2006) Adaptive Changes in Serotonin Neurons of the Raphe Nuclei in 5-HT(4) Receptor Knock-Out Mouse. Eur J Neurosci 24: pp 1053-1062.CrossRefPubMedGoogle Scholar
  18. Cunningham D, Hawthorn J, Pople A, Gazet J C, Ford H T, Challoner T and Coombes R C (1987) Prevention of Emesis in Patients Receiving Cytotoxic Drugs by GR38032F, a Se-lective 5-HT3 Receptor Antagonist. Lancet 1: pp 1461-1463.CrossRefPubMedGoogle Scholar
  19. Davies PA, 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: pp 359-363.CrossRefPubMedGoogle Scholar
  20. Demchyshyn L, Sunahara R K, Miller K, Teitler M, Hoffman B J, Kennedy J L, Seeman P, Van Tol H H and Niznik H B (1992) A Human Serotonin 1D Receptor Variant (5HT1D Beta) En-coded by an Intronless Gene on Chromosome 6. Proc Natl Acad Sci U S A 89: pp 5522-5526.CrossRefPubMedGoogle Scholar
  21. Dubin A E, Huvar R, D’Andrea M R, Pyati J, Zhu J Y, Joy K C, Wilson S J, Galindo J E, Glass C A, Luo L, Jackson M R, Lovenberg T W and Erlander M G (1999) The Pharma-cological and Functional Characteristics of the Serotonin 5-HT(3A) Receptor Are Specifi-cally Modified by a 5-HT(3B) Receptor Subunit. J Biol Chem 274: pp 30799-30810.CrossRefPubMedGoogle Scholar
  22. Dukat M, Smith C, Herrick-Davis K, Teitler M and Glennon R A (2004) Binding of Tryptamine Analogs at H5-HT1E Receptors: A Structure-Affinity Investigation. Bioorg Med Chem 12: pp 2545-2552.CrossRefPubMedGoogle Scholar
  23. Dumuis A, Bouhelal R, Sebben M and Bockaert J (1988a) A 5-HT Receptor in the Central Nervous System, Positively Coupled With Adenylate Cyclase, Is Antagonized by ICS 205 930. Eur J Pharmacol 146: pp 187-188.CrossRefPubMedGoogle Scholar
  24. Dumuis A, Bouhelal R, Sebben M, Cory R and Bockaert J (1988b) A Nonclassical 5-Hydroxytryptamine Receptor Positively Coupled With Adenylate Cyclase in the Central Nervous System. Mol Pharmacol 34: pp 880-887.PubMedGoogle Scholar
  25. Dumuis A, Sebben M and Bockaert J (1989a) BRL 24924: A Potent Agonist at a Non-Classical 5-HT Receptor Positively Coupled With Adenylate Cyclase in Colliculi Neu-rons. Eur J Pharmacol 162: pp 381-384.CrossRefPubMedGoogle Scholar
  26. Dumuis A, Sebben M and Bockaert J (1989b) The Gastrointestinal Prokinetic Benzamide De-rivatives Are Agonists at the Non-Classical 5-HT Receptor (5-HT4) Positively Coupled to Adenylate Cyclase in Neurons. Naunyn Schmiedebergs Arch Pharmacol 340: pp 403-410.CrossRefPubMedGoogle Scholar
  27. Fagni L, Dumuis A, Sebben M and Bockaert J (1992) The 5-HT4 Receptor Subtype Inhibits K+ Current in Colliculi Neurones Via Activation of a Cyclic AMP-Dependent Protein Kinase. Br J Pharmacol 105: pp 973-979.PubMedGoogle Scholar
  28. Fargin A, Raymond J R, Lohse M J, Kobilka B K, Caron M G and Lefkowitz R J (1988) The Genomic Clone G-21 Which Resembles a Beta-Adrenergic Receptor Sequence Encodes the 5-HT1A Receptor. Nature 335: pp 358-360.CrossRefPubMedGoogle Scholar
  29. Foguet M, Hoyer D, Pardo L A, Parekh A, Kluxen F W, Kalkman H O, Stuhmer W and Lubbert H (1992) Cloning and Functional Characterization of the Rat Stomach Fundus Serotonin Receptor. EMBO J 11: pp 3481-3487.PubMedGoogle Scholar
  30. Gaddum J H and Picarelli Z P (1957) Two Kinds of Tryptamine Receptor. Br J Pharmacol Chemother 12: pp 323-328.PubMedGoogle Scholar
  31. Gerald C, Adham N, Kao H T, Olsen M A, Laz T M, Schechter L E, Bard J A, Vaysse P J, Hartig P R, Branchek T A, and Weinshanb R L (1995) The 5-HT4 Receptor: Molecular Cloning and Pharmacological Characterization of Two Splice Variants. EMBO J 14: pp 2806-2815.PubMedGoogle Scholar
  32. Glennon R A, Titeler M and McKenney J D (1984) Evidence for 5-HT2 Involvement in the Mechanism of Action of Hallucinogenic Agents. Life Sci 35: pp 2505-2511.CrossRefPubMedGoogle Scholar
  33. Grailhe R, Grabtree G W and Hen R (2001) Human 5-HT(5) Receptors: the 5-HT(5A) Recep-tor Is Functional but the 5-HT(5B) Receptor Was Lost During Mammalian Evolution. Eur J Pharmacol 418: pp 157-167.CrossRefPubMedGoogle Scholar
  34. Gudermann T, Levy F O, Birnbaumer M, Birnbaumer L and Kaumann A J (1993) Human S31 Serotonin Receptor Clone Encodes a 5-Hydroxytryptamine1E-Like Serotonin Receptor. Mol Pharmacol 43: pp 412-418.PubMedGoogle Scholar
  35. Hamblin M W and Metcalf M A (1991) Primary Structure and Functional Characterization of a Human 5-HT1D-Type Serotonin Receptor. Mol Pharmacol 40: pp 143-148.PubMedGoogle Scholar
  36. Hamblin M W, Metcalf M A, McGuffin R W and Karpells S (1992) Molecular Cloning and Functional Characterization of a Human 5-HT1B Serotonin Receptor: A Homologue of the Rat 5-HT1B Receptor With 5-HT1D-Like Pharmacological Specificity. Biochem Bio-phys Res Commun 184: pp 752-759.CrossRefGoogle Scholar
  37. Hanna M C, Davies P A, Hales T G and Kirkness E F (2000) Evidence for Expression of Heteromeric Serotonin 5-HT(3) Receptors in Rodents. J Neurochem 75: pp 240-247.CrossRefPubMedGoogle Scholar
  38. Heidmann D E, Metcalf M A, Kohen R and Hamblin M W (1997) Four 5-Hydroxytryptamine7 (5-HT7) Receptor Isoforms in Human and Rat Produced by Alternative Splicing: Species Differences Due to Altered Intron-Exon Organization. J Neurochem 68: pp 1372-1381.PubMedCrossRefGoogle Scholar
  39. Hoyer D and Neijt H C (1988) Identification of Serotonin 5-HT3 Recognition Sites in Mem-branes of N1E-115 Neuroblastoma Cells by Radioligand Binding. Mol Pharmacol 33: pp 303-309.PubMedGoogle Scholar
  40. Hoyer D, Waeber C, Pazos A, Probst A and Palacios J M (1988) Identification of a 5-HT1 Recognition Site in Human Brain Membranes Different From 5-HT1A, 5-HT1B and 5-HT1C Sites. Neurosci Lett 85: pp 357-362.CrossRefPubMedGoogle Scholar
  41. Jin H, Oksenberg D, Ashkenazi A, Peroutka S J, Duncan A M, Rozmahel R, Yang Y, Mengod G, Palacios J M and O’Dowd B F (1992) Characterization of the Human 5-Hydroxytryptamine1B Receptor. J Biol Chem 267: pp 5735-5738.PubMedGoogle Scholar
  42. Julius D, Huang K N, Livelli T J, Axel R and Jessell T M (1990) The 5HT2 Receptor Defines a Family of Structurally Distinct but Functionally Conserved Serotonin Receptors. Proc Natl Acad Sci U S A 87: pp 928-932.CrossRefPubMedGoogle Scholar
  43. Julius D, Livelli T J, Jessell T M and Axel R (1989) Ectopic Expression of the Serotonin 1c Receptor and the Triggering of Malignant Transformation. Science 244: pp 1057-1062.CrossRefPubMedGoogle Scholar
  44. Julius D, MacDermott A B, Axel R and Jessell T M (1988) Molecular Characterization of a Functional CDNA Encoding the Serotonin 1c Receptor. Science 241: pp 558-564.CrossRefPubMedGoogle Scholar
  45. Kobilka B K, Frielle T, Collins S, Yang-Feng T, Kobilka T S, Francke U, Lefkowitz R J and Caron M G (1987) An Intronless Gene Encoding a Potential Member of the Family of Receptors Coupled to Guanine Nucleotide Regulatory Proteins. Nature 329: pp 75-79.CrossRefPubMedGoogle Scholar
  46. Kursar J D, Nelson D L, Wainscott D B, Cohen M L and Baez M (1992) Molecular Cloning, Functional Expression, and Pharmacological Characterization of a Novel Serotonin Receptor (5-Hydroxytryptamine2F) From Rat Stomach Fundus. Mol Pharmacol 42: pp 549-557.PubMedGoogle Scholar
  47. Leonhardt S, Herrick-Davis K and Titeler M (1989) Detection of a Novel Serotonin Receptor Subtype (5-HT1E) in Human Brain: Interaction With a GTP-Binding Protein. J Neuro-chem 53: pp 465-471.Google Scholar
  48. Levy FO, Gudermann T, Birnbaumer M, Kaumann A J and Birnbaumer L (1992) Molecular Cloning of a Human Gene (S31) Encoding a Novel Serotonin Receptor Mediating Inhibi-tion of Adenylyl Cyclase. FEBS Lett 296: pp 201-206.CrossRefPubMedGoogle Scholar
  49. Libert F, Parmentier M, Lefort A, Dinsart C, Van Sande J, Maenhaut C, Simons M J, Dumont J E and Vassart G (1989) Selective Amplification and Cloning of Four New Members of the G Protein-Coupled Receptor Family. Science 244: pp 569-572.CrossRefPubMedGoogle Scholar
  50. Lovenberg T W, Baron B M, de Lecea L, Miller J D, Prosser R A, Rea M A, Foye P E, Racke M, Slone A L, Siegel B W (1993a) A Novel Adenylyl Cyclase-Activating Serotonin Receptor (5-HT7) Implicated in the Regulation of Mammalian Circadian Rhythms. Neu-ron 11: pp 449-458.CrossRefGoogle Scholar
  51. Lovenberg T W, Erlander M G, Baron B M, Racke M, Slone A L, Siegel B W, Craft C M, Burns J E, Danielson P E and Sutcliffe J G (1993b) Molecular Cloning and Functional Expression of 5-HT1E-Like Rat and Human 5-Hydroxytryptamine Receptor Genes. Proc Natl Acad Sci U S A 90: pp 2184-2188.CrossRefPubMedGoogle Scholar
  52. Lubbert H, Hoffman B J, Snutch T P, van Dyke T, Levine A J, Hartig P R, Lester H A and Davidson N (1987) CDNA Cloning of a Serotonin 5-HT1C Receptor by Electrophysio-logical Assays of MRNA-Injected Xenopus Oocytes. Proc Natl Acad Sci U S A 84: pp 4332-4336.CrossRefPubMedGoogle Scholar
  53. Maenhaut C, Van Sande J, Massart C, Dinsart C, Libert F, Monferini E, Giraldo E, Ladinsky H, Vassart G and Dumont J E (1991) The Orphan Receptor CDNA RDC4 Encodes a 5-HT1D Serotonin Receptor. Biochem Biophys Res Commun 180: pp 1460-1468.CrossRefPubMedGoogle Scholar
  54. Mahle C D, Nowak H P, Mattson R J, Hurt S D and Yocca F D (1991) [3H]5-Carboxamidotryptamine Labels Multiple High Affinity 5-HT1D-Like Sites in Guinea Pig Brain. Eur J Pharmacol 205: pp 323-324.CrossRefPubMedGoogle Scholar
  55. 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: pp 432-437.CrossRefPubMedGoogle Scholar
  56. Maroteaux L, Saudou F, Amlaiky N, Boschert U, Plassat J L and Hen R (1992) Mouse 5HT1B Serotonin Receptor: Cloning, Functional Expression, and Localization in Motor Control Centers. Proc Natl Acad Sci U S A 89: pp 3020-3024.CrossRefPubMedGoogle Scholar
  57. Matthes H, Boschert U, Amlaiky N, Grailhe R, Plassat J L, Muscatelli F, Mattei M G and Hen R (1993) Mouse 5-Hydroxytryptamine5A and 5-Hydroxytryptamine5B Receptors Define a New Family of Serotonin Receptors: Cloning, Functional Expression, and Chromosomal Localization. Mol Pharmacol 43: pp 313-319.PubMedGoogle Scholar
  58. McAllister G, Charlesworth A, Snodin C, Beer M S, Noble A J, Middlemiss D N, Iversen L L and Whiting P (1992) Molecular Cloning of a Serotonin Receptor From Human Brain (5HT1E): a Fifth 5HT1-Like Subtype. Proc Natl Acad Sci U S A 89: pp 5517-5521.CrossRefPubMedGoogle Scholar
  59. Metcalf M A, McGuffin R W and Hamblin M W (1992) Conversion of the Human 5-HT1D Beta Serotonin Receptor to the Rat 5-HT1B Ligand-Binding Phenotype by Thr355Asn Site Directed Mutagenesis. Biochem Pharmacol 44: pp 1917-1920.CrossRefPubMedGoogle Scholar
  60. Meyerhof W, Obermuller F, Fehr S and Richter D (1993) A Novel Rat Serotonin Receptor: Primary Structure, Pharmacology, and Expression Pattern in Distinct Brain Regions. DNA Cell Biol 12: pp 401-409.CrossRefPubMedGoogle Scholar
  61. Miller K, Weisberg E, Fletcher P W and Teitler M (1992a) Membrane-Bound and Solubilized Brain 5HT3 Receptors: Improved Radioligand Binding Assays Using Bovine Area Postrema or Rat Cortex and the Radioligands 3H-GR65630, 3H-BRL43694, and 3H-LY278584. Synapse 11: pp 58-66.CrossRefPubMedGoogle Scholar
  62. Miller K J, King A, Demchyshyn L, Niznik H and Teitler M (1992b) Agonist Activity of Sumatriptan and Metergoline at the Human 5-HT1D Beta Receptor: Further Evidence for a Role of the 5-HT1D Receptor in the Action of Sumatriptan. Eur J Pharmacol 227: pp 99-102.CrossRefPubMedGoogle Scholar
  63. Miller K J and Teitler M (1992) Quantitative Autoradiography of 5-CT-Sensitive (5-HT1D) and 5-CT-Insensitive (5-HT1E) Serotonin Receptors in Human Brain. Neurosci Lett 136: pp 223-226.CrossRefPubMedGoogle Scholar
  64. Miquel M C, Emerit M B, Bolanos F J, Schechter L E, Gozlan H and Hamon M (1990) Phys-icochemical Properties of Serotonin 5-HT3 Binding Sites Solubilized From Membranes of NG 108-15 Neuroblastoma-Glioma Cells. J Neurochem 55: pp 1526-1536.CrossRefPubMedGoogle Scholar
  65. Monsma Jr. F J, Shen Y, Ward R P, Hamblin M W and Sibley D R (1993) Cloning and Ex-pression of a Novel Serotonin Receptor With High Affinity for Tricyclic Psychotropic Drugs. Mol Pharmacol 43: pp 320-327.PubMedGoogle Scholar
  66. Neijt H C, Plomp J J and Vijverberg H P (1989) Kinetics of the Membrane Current Mediated by Serotonin 5-HT3 Receptors in Cultured Mouse Neuroblastoma Cells. J Physiol 411: pp 257-269.PubMedGoogle Scholar
  67. Oksenberg D, Marsters S A, O’Dowd B F, Jin H, Havlik S, Peroutka S J and Ashkenazi A (1992) A Single Amino-Acid Difference Confers Major Pharmacological Variation Be-tween Human and Rodent 5-HT1B Receptors. Nature 360: pp 161-163.CrossRefPubMedGoogle Scholar
  68. Olsen M A, Nawoschik S P, Schurman B R, Schmitt H L, Burno M, Smith D L and Schechter L E (1999) Identification of a Human 5-HT6 Receptor Variant Produced by Alternative Splicing. Brain Res Mol Brain Res 64: pp 255-263.CrossRefPubMedGoogle Scholar
  69. Pedigo N W, Yamamura H I and Nelson D L (1981) Discrimination of Multiple [3H]5-Hydroxytryptamine Binding Sites by the Neuroleptic Spiperone in Rat Brain. J Neuro-chem 36: pp 220-226.Google Scholar
  70. Peroutka S J and McCarthy B G (1989) Sumatriptan (GR 43175) Interacts Selectively With 5-HT1B and 5-HT1D Binding Sites. Eur J Pharmacol 163: pp 133-136.CrossRefPubMedGoogle Scholar
  71. Plassat J L, Boschert U, Amlaiky N and Hen R (1992) The Mouse 5HT5 Receptor Reveals a Remarkable Heterogeneity Within the 5HT1D Receptor Family. EMBO J 11: pp 4779-4786.PubMedGoogle Scholar
  72. Pritchett D B, Bach A W, Wozny M, Taleb O, Dal Toso R, Shih J C and Seeburg P H (1988) Structure and Functional Expression of Cloned Rat Serotonin 5HT-2 Receptor. EMBO J 7: pp 4135-4140.PubMedGoogle Scholar
  73. Richardson B P, Engel G, Donatsch P and Stadler P A (1985) Identification of Serotonin M-Receptor Subtypes and Their Specific Blockade by a New Class of Drugs. Nature 316: pp 126-131.CrossRefPubMedGoogle Scholar
  74. Roth B L, Craigo S C, Choudhary M S, Uluer A, Monsma Jr. F J , Shen Y, Meltzer H Y and Sibley D R (1994) Binding of Typical and Atypical Antipsychotic Agents to 5-Hydroxytryptamine-6 and 5-Hydroxytryptamine-7 Receptors. J Pharmacol Exp Ther 268: pp 1403-1410.PubMedGoogle Scholar
  75. Saudou F, Boschert U, Amlaiky N, Plassat J L and Hen R (1992) A Family of Drosophila Serotonin Receptors With Distinct Intracellular Signalling Properties and Expression Pat-terns. EMBO J 11: pp 7-17.PubMedGoogle Scholar
  76. Shen Y, Monsma Jr. F J, Metcalf M A, Jose P A, Hamblin M W and Sibley D R (1993) Molecular Cloning and Expression of a 5-Hydroxytryptamine7 Serotonin Receptor Sub-type. J Biol Chem 268: pp 18200-18204.PubMedGoogle Scholar
  77. Smith C, Rahman T, Toohey N, Mazurkiewicz J, Herrick-Davis K and Teitler M (2006) Risperidone Irreversibly Binds to and Inactivates the H5-HT7 Serotonin Receptor. Mol Pharmacol 70: pp 1264-1270.CrossRefPubMedGoogle Scholar
  78. Sumikawa K, Houghton M, Emtage J S, Richards B M and Barnard E A (1981) Active Multi-Subunit ACh Receptor Assembled by Translation of Heterologous MRNA in Xenopus Oocytes. Nature 292: pp 862-864.CrossRefPubMedGoogle Scholar
  79. Suryanarayana S, Daunt D A, Von Zastrow M and Kobilka B K (1991) A Point Mutation in the Seventh Hydrophobic Domain of the Alpha 2 Adrenergic Receptor Increases Its Affin-ity for a Family of Beta Receptor Antagonists. J Biol Chem 266: pp 15488-15492.PubMedGoogle Scholar
  80. Teitler M, Herrick-Davis K and Purohit A (2002) Constitutive Activity of G-Protein Coupled Receptors: Emphasis on Serotonin Receptors. Curr Top Med Chem 2: pp 529-538.CrossRefPubMedGoogle Scholar
  81. Titeler M, Herrick K, Lyon R A, McKenney J D and Glennon R A (1985) [3H]DOB: A Spe-cific Agonist Radioligand for 5-HT2 Serotonin Receptors. Eur J Pharmacol 117: pp 145-146.CrossRefPubMedGoogle Scholar
  82. Titeler M, Lyon R A and Glennon R A (1988) Radioligand Binding Evidence Implicates the Brain 5-HT2 Receptor As a Site of Action for LSD and Phenylisopropylamine Hallucino-gens. Psychopharmacology (Berl) 94: pp 213-216.CrossRefGoogle Scholar
  83. Vane J R (1957) A Sensitive Method for the Assay of 5-Hydroxytryptamine. Br J Pharmacol Chemother 12: pp 344-349.PubMedGoogle Scholar
  84. Waeber C, Dietl M M, Hoyer D and Palacios J M (1989) 5.HT1 Receptors in the Vertebrate Brain. Regional Distribution Examined by Autoradiography. Naunyn Schmiedebergs Arch Pharmacol 340: pp 486-494.PubMedGoogle Scholar
  85. Waeber C, Sebben M, Bockaert J and Dumuis A (1996) Regional Distribution and Ontogeny of 5-HT4 Binding Sites in Rat Brain. Behav Brain Res 73: pp 259-262.CrossRefPubMedGoogle Scholar
  86. Waeber C, Sebben M, Grossman C, Javoy-Agid F, Bockaert J and Dumuis A (1993) [3H]-GR113808 Labels 5-HT4 Receptors in the Human and Guinea-Pig Brain. Neuroreport 4: pp 1239-1242.CrossRefPubMedGoogle Scholar
  87. Waeber C, Sebben M, Nieoullon A, Bockaert J and Dumuis A (1994) Regional Distribution and Ontogeny of 5-HT4 Binding Sites in Rodent Brain. Neuropharmacology 33: pp 527-541.CrossRefPubMedGoogle Scholar
  88. Wainscott D B, Cohen M L, Schenck K W, Audia J E, Nissen J S, Baez M, Kursar J D, Lucaites V L and Nelson D L (1993) Pharmacological Characteristics of the Newly Cloned Rat 5-Hydroxytryptamine2F Receptor. Mol Pharmacol 43: pp 419-426.PubMedGoogle Scholar
  89. Weinshank R L, Zgombick J M, Macchi M J, Branchek T A and Hartig P R (1992) Human Serotonin 1D Receptor Is Encoded by a Subfamily of Two Distinct Genes: 5-HT1D Alpha and 5-HT1D Beta. Proc Natl Acad Sci U S A 89: pp 3630-3634.CrossRefPubMedGoogle Scholar
  90. Weisberg E and Teitler M. (1992) Novel High-Affinity 3H-Serotonin Binding Sites in Rat and Bovine Brain Tissue. Drug Dev Res 26: pp 225-229.CrossRefGoogle Scholar
  91. Xiong W C and Nelson D L (1989) Characterization of a [3H]-5-Hydroxytryptamine Binding Site in Rabbit Caudate Nucleus That Differs From the 5-HT1A, 5-HT1B, 5-HT1C and 5-HT1D Subtypes. Life Sci 45: pp 1433-1442.CrossRefPubMedGoogle Scholar
  92. Yagaloff K A and Hartig P R (1985) 125I-Lysergic Acid Diethylamide Binds to a Novel Serotonergic Site on Rat Choroid Plexus Epithelial Cells. J Neurosci 5: pp 3178-3183.PubMedGoogle Scholar
  93. Zgombick J M, Schechter L E, Macchi M, Hartig P R, Branchek T A and Weinshank R L (1992) Human Gene S31 Encodes the Pharmacologically Defined Serotonin 5-Hydroxytryptamine1E Receptor. Mol Pharmacol 42: pp 180-185.PubMedGoogle Scholar

Copyright information

© Springer Science+Business Media, LLC 2007

Authors and Affiliations

  • Milt Teitler
    • 1
  1. 1.Center for Neuropharmacology and NeuroscienceAlbany Medical CollegeAlbanyUSA

Personalised recommendations