Skip to main content

Molecular Biology and Transductional Characteristics of 5-HT Receptors

  • Chapter
Serotoninergic Neurons and 5-HT Receptors in the CNS

Part of the book series: Handbook of Experimental Pharmacology ((HEP,volume 129))

Abstract

Serotonin is an ancient neurotransmitter. Phylogenetic comparisons suggest that the earliest serotonin receptor may have first appeared over 700 million years ago (Peroutka and Howell 1994). It is released from fiber tracts originating in primitive brainstem regions (the raphe nuclei of the brainstem reticular formation), and is found in species as ancient as Aplysia, Caenorhabditis elegans, and Drosophila. In addition, its synapses and receptors are widely distributed throughout the brain, serving many broad modulatory roles for diverse brain functions. It is not surprising, then, that serotonin receptors are primarily of the G-protein-coupled, 7-transmembrane receptor (7TM) class since these receptors couple to enzymatic and ion channel-modulating second messenger pathways (primarily adenylate cyclase, phosphoinositide turnover, and potassium channel modulation) which exhibit time constants in the second to millisecond range, consistent with broad signal modulation and gain-setting functions in the brain.

This is a preview of subscription content, log in via an institution to check access.

Access this chapter

Chapter
USD 29.95
Price excludes VAT (USA)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever
eBook
USD 39.99
Price excludes VAT (USA)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever
Softcover Book
USD 54.99
Price excludes VAT (USA)
  • Compact, lightweight edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info

Tax calculation will be finalised at checkout

Purchases are for personal use only

Institutional subscriptions

Preview

Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.

References

  • Adham N, Romanienko P, Hartig P, Weinshank RL, Branchek T (1992) The rat 5- hydroxytryptamine1B receptor is the species homologue of the human 5- hydroxytryptamine1Dß . Mol Pharmacol 41: 1–7

    PubMed  CAS  Google Scholar 

  • Adham N, Ellerbrock B, Hartig P, Weinshank RL, Branchek T (1993a) Receptor reserve masks partial agonist activity of drugs in a cloned rat 5-hydroxytryptamine1B receptor expression system. Mol Pharmacol 43: 427–433

    PubMed  CAS  Google Scholar 

  • Adham N, Kao H-T, Schechter LE, Bard J, Olsen M, Urquhart D, Durkin M, Hartig PR, Weinshank RL, Branchek TA (1993b) 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 USA 90: 408–412

    PubMed  CAS  Google Scholar 

  • Adham N, Borden LA, Schechter LE, Gustafon EL, Cochran TL, Pierre J-J, Weinshank RL, Branchek TA (1993c) Cell-specific coupling of the cloned human 5-HT1F receptor to multiple signal transduction pathways. Naunyn Schmiedebergs Arch Pharmacol 348: 566–575

    PubMed  CAS  Google Scholar 

  • Adham N, Vaysse PJ-J, Weinshank RL, Branchek TA (1994a) The cloned human 5- HT1E receptor couples to inhibition and activation of adenylyl cyclase via two distinct pathways in transfected BS-C-1 cells. Neuropharmacology 33: 403–410

    PubMed  CAS  Google Scholar 

  • Adham N, Tamm JA, Salon JA, Vaysse PJJ, Weinshank RL, Branchek TA (1994b) A single point mutation increases the affinity of serotonin 5-HT1Dα, 5-HT1Dß , 5-HT, and 5-HT1F receptors for ß-adrenergic antagonists. Neuropharmacology 33: 387–391

    PubMed  CAS  Google Scholar 

  • Albert PR, Zhou Q-Y, Van Tol HHM, Bunzow JR, Civelli O (1990) Cloning, functional expression, and mRNA tissue distribution of the rat 5-hydroxytryptamine1A receptor gene. J Biol Chem 265: 5825–5832

    PubMed  CAS  Google Scholar 

  • Amlaiky N, Ramboz S, Boschert U, Plassat J-L, Hen R (1992) Isolation of a mouse ″5- HT1E-like serotonin receptor expressed predominantly in the hippocampus. J Biol Chem 267: 19761–19765

    PubMed  CAS  Google Scholar 

  • Andrade R, Malenka RC, Nicoll RA (1986) AG protein couples serotonin and GABAB receptors to the same channels in hippocampus. Science 234: 1261–1265

    PubMed  CAS  Google Scholar 

  • Bach AWJ, Unger L, Sprengel R, Mengod G, Palacios J, Seeburg PH, Voigt MM (1993) Structure, functional expression and spatial distribution of a cloned cDNA encoding a rat 5-HT1D-like receptor. J Receptor Res 13: 479–502

    CAS  Google Scholar 

  • Bard JA, Zgombick J, Adham N, Vaysse P, Branchek TA Weinshank RL, (1993) Cloning of a novel human serotonin receptor (5-HT7) positively linked to adenylate cyclase. J Biol Chem 268: 23422–23426

    PubMed  CAS  Google Scholar 

  • Bard JA, Nawoschik SP, O’Dowd BF, George SR, Branchek TA, Weinshank RL (1995) The human serotonin 5-hydroxytryptamine1D receptor pseudogene is transcribed. Gene 153: 295–296

    PubMed  CAS  Google Scholar 

  • Beer MS, Middlemiss DN, McAllister G (1993) 5-HT1like receptors: six down and still counting. Trends Pharmacol Sci 14: 228–231

    PubMed  CAS  Google Scholar 

  • Bertin B, Freissmuth M, Breyer RM, Schutz W, Strosberg AD, Marullo S (1992) Functional expression of the human serotonin 5-HT1A receptor in Escherichia coli. J Biol Chem 267: 8200–8206

    PubMed  CAS  Google Scholar 

  • Bevan P, Cools AR, Archer T (1989) Behavioural pharmacology of 5-HT. Erlbaum, Hillsdale, New Jersey

    Google Scholar 

  • Boess FG, Martin IL (1994) Molecular biology of 5-HT receptors. Neuropharmacology 33: 275–317

    PubMed  CAS  Google Scholar 

  • Bonhaus DW, Stefanich E, Loury DN, Hsu SA, Eglen RM, Wong EH (1995) Allosteric interactions among agonists and antagonists at 5-hydroxytryptamine3 receptors. J Neurochem 65: 104–110

    PubMed  CAS  Google Scholar 

  • Bourson A, Borroni E, Austin RH, Monsma FJ, Sleight AJ (1995) Determination of the role of the 5-HT6 receptor in the rat brain: a study using antisense oligonucleotides. J Pharmacol Exp Ther 274: 173–180

    PubMed  CAS  Google Scholar 

  • Branchek TA (1995) 5HT4, 5HT6, 5HT7; molecular pharmacology of adenylate cyclase stimulating receptors. Neuroscience 7: 375–382

    CAS  Google Scholar 

  • Branchek TA, Adham N, Macchi M, Kao HT, Hartig PR (1990) [3H]-DOB(4-bromo- 2,5-dimethoxyphenylisopropylamine) and [3H] ketanserin label two affinity states of the cloned human 5-hydroxytrypamine2 receptor. Mol Pharmacol 38: 604–609

    PubMed  CAS  Google Scholar 

  • Brüss M, Bühlen M, Erdmann J, Göthert M, Bönisch H (1995) Binding properties of the naturally occurring human 5-HT1A receptor variant with the Ile28Val substitution in the extracellular domain. Naunyn Schmiedebergs Arch Pharmacol 352: 455–458

    PubMed  Google Scholar 

  • Bühlen M, Brüss M, Bönisch H, Göthert M (1966) Modified ligand binding properties of the naturally occurring Phe-124-CγS variant of the human 5-HT1Dß receptor. Naunyn Schmiedebergs Arch Pharmacol 353(Suppl):R91

    Google Scholar 

  • Carey J, Hamilton J O’C, Flynn J, Smith G (1995) The gene kings. Business Week, May 8, pp 72–78

    Google Scholar 

  • Cases O, Seif I, Grimsby J, Gaspar P, Chen K, Pournin S (1995) Aggressive behavior and altered amounts of brain serotonin and norepinephrine in mice lacking MAO A. Science 268: 1763–1766

    PubMed  CAS  Google Scholar 

  • Cerutis DR, Hass NA, Iversen LJ, Bylund DB (1994) The cloning and expression of an OK cell cDNA encoding a 5-hydroxytryptamine1B receptor. Mol Pharmacol 45: 20–28

    PubMed  CAS  Google Scholar 

  • Chanda PK, Minchin MC, Davis AR, Greenberg L, Reilly Y, McGregor WH, Bhat R, Lubeck MD, Mizutani S, Hung PP (1993) Identification of residues important for ligand binding to the human 5-hydroxytryptamine1A serotonin receptor. Mol Pharmacol 43: 516–520

    PubMed  CAS  Google Scholar 

  • Chen C, Rainnie DG, Greene RW, Tonegawa S (1994) Abnormal fear response and aggressive behavior in mutant mice deficient for alpha-calcium-calmodulin kinase II. Science 266: 291–294

    PubMed  CAS  Google Scholar 

  • Choudhary MS, Craigo S, Roth BL (1993) A single point mutation (Phe340→Leu340) of a conserved phenylalanine abolishes 4-[125I]iodo(2,5dimethoxy)- phenylisopropylamine and [3H]mesulergine but not [3H]ketanserin binding to 5- hydroxytryptamine2 receptors. Mol Pharmacol 43: 755–761

    PubMed  CAS  Google Scholar 

  • Codina J, Yatani A, Grenet D, Brown AM, Birnbaumer L (1987) The α-subunit of the GTP binding protein Gk opens atrial potassium channels. Science 236: 442–445

    PubMed  CAS  Google Scholar 

  • Demchyshyn L, Sunahara RK, Miller K, Teitler M, Hoffman BJ, Kennedy JL, Seeman P, Van Tol HHM, Niznik HB (1992) A human serotonin1D receptor variant (5HT1Dß ) encoded by an intronless gene on chromosome 6. Biochemistry 89: 5522–5526

    CAS  Google Scholar 

  • Downie DL, Hope AG, Lambert JJ, Peters JA, Blackburn TP, Jones BJ (1994) Pharmacological characterization of the apparent splice variants of the murine 5-HT3 R-A subunit expressed in Xenopus laevis oocytes. Neuropharmacology 33: 473–482

    PubMed  CAS  Google Scholar 

  • Du Y-L, Wilcox BD, Jeffrey JJ (1995) Regulation of rat 5-hydroxytryptamine type 2 receptor gene activity: identification of cis elements that mediate basal and 5- hydroxytryptamine-dependent gene activation. Mol Pharmacol 47: 915–922

    PubMed  CAS  Google Scholar 

  • Erlander MG, Lovenberg TW, Baron BM, de Lecea L, Danielson PE, Racke M, Slone AL, Siegel BW, Foye PE, Cannon K, Burns JE, Sutcliffe JG (1993) Two members of a distinct subfamily of 5-hydroxytryptamine receptors differentially expressed in rat brain. Proc Natl Acad Sci USA 90: 3452–3456

    PubMed  CAS  Google Scholar 

  • Fan P, Oz M, Zhang L, Weight FF (1995) Effect of cocaine on the 5-HT3 receptor- mediated ion current in Xenopus oocytes. Brain Res 673: 181–184

    PubMed  CAS  Google Scholar 

  • Fargin A, Raymond JR, Lohse MJ, Kobilka BK, Caron MC, Lefkowitz (1988) The genomic clone G-21 which resembles a ß-adrenergic receptor sequence encodes the 5-HT1A receptor. Nature 335: 358–360

    PubMed  CAS  Google Scholar 

  • Fargin A, Raymond JR, Regan JW, Cotecchia S, Lefkowitz RJ, Caron MG (1989) Effector coupling mechanisms of the cloned 5-HT1A receptor. J Biol Chem 264: 14848–14852

    PubMed  CAS  Google Scholar 

  • Foguet M, Nguyen H, Le Huong, Lübbert H (1992a) Structure of the mouse 5-HT1C, 5- HT2 and stomach fundus serotonin receptor genes. Neuroreport 3: 345–348

    PubMed  CAS  Google Scholar 

  • Foguet M, Hoyer D, Pardo LA, Parekh A, Kluxen FW, Kalkman HO, Stühmer W, Lübbert H (1992b) Cloning and functional characterization of the rat stomach fundus serotonin receptor. EMBO J 11: 3481–3487

    PubMed  CAS  Google Scholar 

  • Gerald C, Adham N, Kao H-T, Olsen MA, Laz TM, Schechter LE, Bard JA, Vaysse PJJ, Hartig PR, Branchek TA, Weinshank RL (1995) The 5-HT4 receptor: molecular cloning and pharmacological characterization of two splice variants. EMBO J 14: 2806–2815

    PubMed  CAS  Google Scholar 

  • Grailhe R, Ramboz S, Boschert U, Hen R (1995) The 5-HT5 receptors: characterization of the human 5-HT5A receptor; absence of the human 5-HT5B receptor; knockout of the mouse 5-HT5A receptor. Soc Neurosci Abst 21: 1856

    Google Scholar 

  • Guan XM, Peroutka SJ, Kobilka BK (1992) Identification of a single amino acid residue responsible for the binding of a class of ß-adrenergic receptor antagonists to 5-hydroxytryptamine1A receptors. Mol Pharmacol 41: 695–698

    PubMed  CAS  Google Scholar 

  • Gudermann T, Levy FO, Birnbaumer M, Birnbaumer L, Kaumann AJ (1993) Human S31 serotonin receptor clone encodes a 5-hydroxytryptamine1E-like serotonin receptor. Mol Pharmacol 43: 412–418

    PubMed  CAS  Google Scholar 

  • Hamblin MW, Metcalf MA (1991) Primary structure and functional characterization of a human 5HT1D-type serotonin receptor. Mol Pharmacol 40: 143–148

    PubMed  CAS  Google Scholar 

  • Hamblin MW, McGuffin RW, Metcalf MA, Dorsa DM, Merchang KM (1992) Distinct 5-HT1B and 5HT1D serotonin receptors in rat: structural and pharmacological comparison of the two cloned receptors. Mol Cell Neurosci 3: 578–587

    PubMed  CAS  Google Scholar 

  • Hamel E, Gregoire L, Lau B (1993) 5-HT1 receptors mediating contraction in bovine cerebral arteries: a model for human cerebrovascular “5-HT1Dß ” receptors. Eur J Pharmacol 242: 75–82

    PubMed  CAS  Google Scholar 

  • Hargreaves AC, Lummis SCR, Taylor CW (1994) Ca2+ permeability of cloned and native 5-hydroxytryptamine type 3 receptors. Mol Pharmacol 46: 1120–1128

    PubMed  CAS  Google Scholar 

  • Harrington MA, Shaw K, Zhong P, Ciaranello RD (1994) Agonist-induced desensitization and loss of high-affinity binding sites of stably expressed human 5-HT1A receptors. J Pharmacol Exp Ther 268: 1098–1106

    PubMed  CAS  Google Scholar 

  • Hartig PR, Brancheck TA, Weinshank RL (1992) A subfamily of 5-HT1D receptor genes. Trends Pharm Sci 13: 152–159

    PubMed  CAS  Google Scholar 

  • Hartig PR, Hoyer D, Humphrey PPA, Martin GR (1996) Alignment of receptor nomenclature with the human genome: classification of 5-HT1B and 5-HT1D receptor subtypes. Trends Pharm Sci 17: 103–105

    PubMed  CAS  Google Scholar 

  • Hilakivi-Clarke LA, Goldberg R (1993) Effects of tryptophan and serotonin uptake inhibitors on behavior in male transgenic transforming growth factor alpha mice. Eur J Pharmacol 237: 101–108

    PubMed  CAS  Google Scholar 

  • Ho BY, Karschin A, Branchek T, Davidson N, Lester HA (1992) The role of conserved aspartate and serine residues in ligand binding and in function of the 5-HT1A receptor: a site-directed mutation study. FEBS Lett 312: 259–262

    PubMed  CAS  Google Scholar 

  • Hoffman BJ, Mezey E (1989) Distribution of serotonin 5-HT1C receptor mRNA in adult rat brain. FEBS Lett 247: 453–462

    PubMed  CAS  Google Scholar 

  • Hope AG, Downie DL, Sutherland L, Lambert JJ, Peters JA, Burchell B (1993) Cloning and functional expression of an apparent splice variant of the murine 5- HT3 receptor A subunit. Eur J Pharmacol 245: 187–192

    PubMed  CAS  Google Scholar 

  • Hoyer D, Middlemiss DN (1989) Species differences in the pharmacology of terminal 5-HT autoreceptors in mammalian brain. Trends Pharmacol Sci 10: 130–132

    PubMed  CAS  Google Scholar 

  • Hoyer D, Clarke DE, Fozard JR, Hartig PR, Martin GR, Mylecharane EJ, Saxena PR, Humphrey PPA (1994) VII. International union of pharmacology classification of receptors for 5-hydroxytryptamine (serotonin). Pharmacol Rev 46: 157–203

    PubMed  CAS  Google Scholar 

  • Hussy N, Lukas W, Jones KA (1994) Functional properties of a cloned 5-hydroxytryptamine ionotropic receptor subunit: comparison with native mouse receptors. J Physiol 481: 311–322

    PubMed  CAS  Google Scholar 

  • Jin H, Oksenberg D, Ashkenazi A, Peroutka SJ, Duncan AMV, Rozmahel R, Yang Y, Mengod G, Palacios JM, O’Dowd BF (1992) Characterization of the human 5- hydroxytryptamine1B receptor. J Biol Chem 267: 5735–5738

    PubMed  CAS  Google Scholar 

  • Johnson MP, Loncharich RJ, Baez M, Nelson DL (1994) Species variations in transmembrane region V of the 5-hydroxytryptamine type 2A receptor alter the structure-activity relationship of certain ergolines and tryptamines, Mol Pharmacol 45: 277–286

    PubMed  CAS  Google Scholar 

  • Johnson MP, Baez M, Kursar JD, Nelson DL (1995) Species differences in 5-HT2a receptors: cloned pig and rhesus monkey 5-HT2a receptors reveal conserved transmembrane homology to the human rather than rat sequence. Biochim Biophys Acta 1236: 201–206

    PubMed  Google Scholar 

  • Julius D (1991) Molecular biology of serotonin receptors. Annu Rev Neurosci 14: 335–360

    PubMed  CAS  Google Scholar 

  • Julius D, MacDermott AB, Axel R, Jessell TM (1988) Molecular characterization of a functional cDNA encoding the serotonin 1c receptor. Science 241: 558–564

    PubMed  CAS  Google Scholar 

  • Julius D, Livelli TJ, Jessell TM, Axel R (1989) Ectopic expression of the serotonin 1c receptor and the triggering of malignant transformation. Science 244: 1057–1062

    PubMed  CAS  Google Scholar 

  • Julius D, Huang KN, Livelli TJ, Axel R, Jessell TM (1990) The 5HT2 receptor defines a family of structurally distinct but functionally conserved serotonin receptors. Proc Natl Acad Sci USA 87: 928–932

    PubMed  CAS  Google Scholar 

  • Kao HT, Adham N, Olsen M, Weinshank RL, Branchek TA, Hartig P (1992) Site- directed mutagenesis of a single residue changes the binding properties of the serotonin 5-HT2 receptor from a human to a rat pharmacology. FEBS Lett 307: 324–328

    PubMed  CAS  Google Scholar 

  • Karschin A, Ho BY, LaBarca C, Elroy-Stein O, Moss B, Davidson N, Lester, HA (1991) Heterologously expressed serotonin1A receptors couple to muscarinic K+ channels in heart. Proc Natl Acad Sci USA 88: 5694–5698

    PubMed  CAS  Google Scholar 

  • Kobilka BK, Frielle T, Collins S, Yang-Feng T, Kobilka S, Francke U, Lefkowitz J, Caron MC (1987) An intronless gene encoding a potential member of the family of receptors coupled to guanine nucleotide regulatory proteins. Nature 329: 75–79

    PubMed  CAS  Google Scholar 

  • Kohen R, Metcalf MA, Khan N, Druck T, Huebner K, Lachowicz JE, Meltzer HY, Sibley DR, Roth BL Hamblin MW (1996) Cloning, characterization, and chromosomal localization of a human 5-HT6 serotonin receptor. J Neurochem 66: 47–56

    PubMed  CAS  Google Scholar 

  • Kursar JD, Nelson DL, Wainscott DB, Cohen ML, Baez M (1992) Molecular cloning, functional expression, and pharmacological characterization of a novel serotonin receptor (5-hydroxytryptamine 2F) from rat stomach fundus. Mol Pharmacol 42: 549–557

    PubMed  CAS  Google Scholar 

  • Leonhardt S, Herrick-Davis K, Titeler M (1989) Detection of a novel serotonin receptor subtype (5-HT1E) in human brain: interaction with a GTP-binding protein. J Neurochem 53: 465–471

    PubMed  CAS  Google Scholar 

  • Levy FO, Gudermann T, Perez-Reyes E, Birnbaumer M, Kaumann AJ, Birnbaumer L (1992a) Molecular cloning of a human serotonin receptor (S12) with a pharmacological profile resembling that of the 5-HT1D subtype. J Biol Chem 267: 7553–7562

    PubMed  CAS  Google Scholar 

  • Levy FO, Gudermann T, Birnbaumer M, Kaumann AJ, Birnbaumer L (1992b) Molecular cloning of a human gene (S31) encoding a novel serotonin receptor mediating inhibition of adenylyl cyclase. FEBS Lett 296: 201–206

    PubMed  CAS  Google Scholar 

  • Libert F, Parmentier M, Lefort A, Dinsart C, Van Sande J, Maenhaut C, Simons MJ, Dumont JE, Vassart G (1989) Selective amplification and cloning of four new members of the G-protein-coupled receptor family. Science 244: 569–572

    PubMed  CAS  Google Scholar 

  • Loric S, Launay JM, Colas JF, Maroteaux L (1992) New mouse 5-HT2 like receptor expression in brain, heart and intestine. FEBS Lett 312: 203–207

    PubMed  CAS  Google Scholar 

  • Lovenberg TW, Erlander MG, Baron BM, Racke M, Slone AL, Siegel BW, Craft CM, Burns JE, Danielson PE, Sutcliffe (1993a) Molecular cloning and functional expression of 5-HT1E-like rat and human 5-hydroxytryptamine receptor genes. Proc Natl Acad Sci USA 90: 2184–2188

    PubMed  CAS  Google Scholar 

  • Lovenberg TW, Baron BM, deLecea L, Miller JD, Prosser RA, Rea MA, Foye PE, Racke M, Slone AL, Siegel BW, Danielson PE, Sutcliffe JG, Erlander MG (1993b) A novel adenylyl cyclase-activating serotonin receptor (5-HT7) implicated in the regulation of mammalian circadian rhythms. Neuron 11: 449–458

    PubMed  CAS  Google Scholar 

  • Lübbert H, Hoffman BJ, Snutch TP, van Dyke T, Levine AJ, Hartig PR, Lester HA, Davidson N (1987) cDNA cloning of a serotonin 5-HT1C receptor by electrophysiological assays of mRNA-injected Xenopus oocytes. Proc Natl Acad Sci USA 84: 4332–4336

    PubMed  Google Scholar 

  • Lucas JJ, Hen R (1995) New players in the 5-HT receptor field: genes and knockouts. Trends Pharmacol Sci 16: 246–252

    PubMed  CAS  Google Scholar 

  • Machu TK, Harris RA (1994) Alcohols and anesthetics enhance the function of 5- hydroxytryptamine3 receptors expressed in Xenopus laevis oocytes. J Pharmacol Exp Ther 271: 898–905

    PubMed  CAS  Google Scholar 

  • Maenhaut C, Van Sande J, Massart C, Dinsart C, Libert F, Monferini E, Giraldo E, Ladinsky H, Vassart G, Dumont JE (1991) The orphan receptor cDNA RDC4 encodes a 5-HT1D serotonin receptor. 180: 1460–1468

    Google Scholar 

  • Maricq AV, Peterson AS, Brake AJ, Myers RM, Julius D (1991) Primary structure and functional expression of the 5HT3 receptor, a serotonin-gated ion channel. Science 254: 432–437

    PubMed  CAS  Google Scholar 

  • Maroteaux L, Saudou F, Amlaiky N, Boschert U, Plassat JL, Hen R (1992) Mouse 5HT1B serotonin receptor: cloning, functional expression, and localization in motor control centers. Neurobiology 89: 3020–3024

    CAS  Google Scholar 

  • Matthes H, Boschert U, Amlaiky N, Grailhe R, Plassat JL, Muscatelli F, Mattei MG, 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: 313–319

    PubMed  CAS  Google Scholar 

  • McAllister G, Charlesworth A, Snodin C, Beer MS, Noble AJ, Middlemiss DN, Iversen LL, Whiting P (1992) Molecular cloning of a serotonin receptor from human brain (5HT1E): a fifth 5HT1-like subtype. Neurobiology 89: 5517–5521

    CAS  Google Scholar 

  • Meller E, Goldstein M, Bohmaker K (1990) Receptor reserve for 5- hydroxytryptamine1A-mediated inhibition of serotonin synthesis: possible relationship to anxiolytic properties of 5-hydroxytryptamine1A agonists. Mol Pharmacol 37: 231–237

    PubMed  CAS  Google Scholar 

  • Metcalf MA, McGuffin RW, Hamblin MW (1992) Conversion of the human 5-HT1Dß serotonin receptor to the rat 5-HT1B ligand-binding phenotype by Thr355Asn site directed mutagenesis. Biochem Pharmacol 44: 1917–1920

    PubMed  CAS  Google Scholar 

  • Meyerhof W, Obermuller F, Fehr S, Richter D (1993) A novel serotonin receptor: primary structure, pharmacology, and expression pattern in distinct brain regions. DNA Cell Biol 12: 402–409

    Google Scholar 

  • Miquel MC, Doucet E, Bone C, Mestikawy S EL, Matthiessen L, Daval G, Verge D, Hamon M (1991) Central serotoninłA receptors: respective distribution of encoding mRNA, receptor protein and binding sites by in situ hybridization histochemistry, radioimmunohistochemistry and autoradiographic mapping in the rat brain. Neurochem Int 19: 453–465

    CAS  Google Scholar 

  • Miquel MC, Emerit MB, Gingrich JA, Nosjean A, Hamon M, Mestikawy S (1995) Developmental changes in the differential expression of two serotonin 5-HT3 receptor splice variants in the rat. J Neurochem 65: 475–483

    PubMed  CAS  Google Scholar 

  • Miyake A, Mochizuki S, Takemoto Y, Akuzawa S (1995) Molecular cloning of human 5-hydroxytryptamine3 receptor: heterogeneity in distribution and function among species. Mol Pharmacol 48: 407–416

    PubMed  CAS  Google Scholar 

  • Monsma FJ Jr, Shen Y, Ward RP, Hamblin MW, Sibley DR (1993) Cloning and expression of a novel serotonin receptor with high affinity for tricyclic psychotropic drugs. Mol Pharmacol 43: 320–327

    PubMed  CAS  Google Scholar 

  • Nguyen T, Marchese A, Kennedy JL, Petronis A, Peroutka SJ, Wu PH, O’Dowd BF (1993) An Alu repeat interrupts a human 5-hydroxytryptamine1D receptor pseudogene. Gene 124: 295–301

    PubMed  CAS  Google Scholar 

  • Oakey RJ, Caron MG, Lekfowitz RJ, Seldin MF (1991) Genomic organization of adrenergic and serotonin receptors in the mouse: linkage mapping of sequence- related genes provides a method for examining mammalian chromosome evolution, Genomics 10: 338–344

    PubMed  CAS  Google Scholar 

  • Oksenberg D, Marsters SA, O’Dowd BF, Jin H, Havlik S, Peroutka SJ, Ashkenazi A (1992) A single amino-acid difference confers major pharmacological variation between human and rodent 5-HT1B receptors. Nature 360: 161–163

    PubMed  CAS  Google Scholar 

  • Parker EM, Grisel DA, Iben LG, Shapiro RA (1993) A single amino acid difference accounts for the pharmacological distinctions between the rat and human 5- hydroxytryptamine1B receptors. J Neurochem 60: 380–383

    PubMed  CAS  Google Scholar 

  • Pauwels PJ, Van Gompel P, Leysen JE (1993) Activity of serotonin (5-HT) receptor agonists, partial agonists and antagonists at cloned human 5-HT1A receptors that are negatively coupled to adenylate cyclase in permanently transfected HeLa cells. Biochem Pharmacol 45: 375–383

    PubMed  CAS  Google Scholar 

  • Peroutka SJ, Howell TA (1994) The molecular evolution of G-protein-coupled receptors: focus on 5-hydroxytryptamine receptors. Neuropharmacology 33: 319–324

    PubMed  CAS  Google Scholar 

  • Peters JA, Malone HM, Lambert JJ (1992) Recent advances in the electrophysiological characterization of 5-HT3 receptors. Trends Pharm Sci 13: 391–397

    PubMed  CAS  Google Scholar 

  • Plassat JL, Boschert U, Amlaiky N, Hen R (1992) The mouse 5HT5 receptor reveals a remarkable heterogeneity within the 5HT1D receptor family. EMBO J 11: 4779–4786

    PubMed  CAS  Google Scholar 

  • Plassat JL, Amlaiky N, Hen R, (1993) Molecular cloning of a mammalian serotonin receptor that activates adenylate cyclase. Mol Pharmacol 44: 229–236

    PubMed  CAS  Google Scholar 

  • Pritchett DB, Bach AWJ, Wozny M, Taleb O, Dal Toso R, Shih JC, Seeburg PH (1988) Structure and functional expression of a cloned rat serotonin 5HT-2 receptor. EMBO J 7: 4135–4140

    PubMed  CAS  Google Scholar 

  • Raymond JR, Fargin A, Middleton JP, Craff JM, Haupt DM, Caron MG, Lefkowitz RJ, Dennis VW (1989) The human 5-HT1A receptor expressed in HeLa cells stimulates sodium-dependent phosphate uptake via protein kinase C. J Biol Chem 264: 21943–21950

    PubMed  CAS  Google Scholar 

  • Rees S, den Daas I, Foord S, Goodson S, Bull D, Kilpatrick G, Lee M (1994) Cloning and characterisation of the human 5-HT5A serotonin receptor. FEBS Lett 355: 242–246

    PubMed  CAS  Google Scholar 

  • Ruat M, Traiffort E, Arrang JM, Tardivel-Lacombe J, Diaz J, Leurs R, Schwartz JC (1993a) A novel rat serotonin (5-HT6) receptor: molecular cloning, localization and stimulation of cAMP accumulation. Biochem Biophys Res Comm 193: 268–276

    PubMed  CAS  Google Scholar 

  • Ruat M, Traiffort E, Leurs R, Tardivel-Lacombe J, Diaz J, Arrang JM, Schwartz JC (1993b) Molecular cloning, characterization, and localization of a high-affinity serotonin receptor (5-HT7) activating cAMP formation. Proc Natl Acad Sci USA 90: 8547–8551

    PubMed  CAS  Google Scholar 

  • Saltzman AG, Morse B, Whitman MM, Ivanshchenko Y, Jaye M, Felder S (1991) Cloning of the human serotonin 5-HT2 and 5-HT1C receptor subtypes. Biochem Biophys Res Comm 181: 1469–1478

    PubMed  CAS  Google Scholar 

  • Saudou F, Amara DA, Dierich A, LeMeur M, Ramboz S, Segu L, Buhot MC, Hen R (1994) Enhanced aggressive behavior in mice lacking 5-HT1B receptor. Science 265: 1875–1878

    PubMed  CAS  Google Scholar 

  • Schmuck K, Ullmer C, Engles P, Lübbert H (1994) Cloning and functional characterization of the human 5-HT2B serotonin receptor. FEBS Lett 342: 85–90

    PubMed  CAS  Google Scholar 

  • Shen Y, Monsma FJ, Metcalf MA, Jose PA, Hamblin MW, Sibley DR (1993) Molecular cloning and expression of a 5-hydroxytryptamine7 serotonin receptor subtype. J Biol Chem 268: 18200–18204

    PubMed  CAS  Google Scholar 

  • Shuck ME, Veldman SA, Bienkowski MJ (1993) Cloning, sequencing and phylogenetic analysis of a human 5-hydroxytryptamine1D receptor pseudogene. Gene 137 :339–344

    PubMed  CAS  Google Scholar 

  • Spengler D, Waeber C, Pantaloni C, Holsboer F, Bockaert J, Seeburg PH, Journot L (1993) Differential signal transduction by five splice variants of the PACAP receptor. Nature 365: 170–175

    PubMed  CAS  Google Scholar 

  • Spurlock G, Buckland P, O’Donovan M, McGuffin P (1994) Lack of effect of antidepressant drugs on the levels of mRNAs encoding serotonergic receptors, synthetic enzymes and 5HT transporter. Neuropharmacology 33: 433–440

    PubMed  CAS  Google Scholar 

  • Stam NJ, Van Huizen F, Van Alebeek C, Brands J, Dijkema R, Tonnaer J ADM, Olijve W (1992) Genomic organization coding sequence and functional expression of human 5-HT2 and 5-HT1A receptor genes. Eur J Pharmacol Mol Pharmacol Section 227: 153–162

    CAS  Google Scholar 

  • Stam NJ, Vanderheyden P, van Alebeek C, Klomp J, deBoer T, van Delft AML, Olijve W (1994) Genomic organisation and functional expression of the gene encoding the human serotonin 5-HT2c receptor. Eur J Pharmacol 269: 339–348

    PubMed  CAS  Google Scholar 

  • Strader CD, Candelore MR, Hill WS, Sigal RS, Dixon RAF (1989) Identification of two serine residues involved in agonist activation of the β-adrenergic receptor. J Biol Chem 264: 13572–13578

    PubMed  CAS  Google Scholar 

  • Strader CD, Ming Fong T, Tota MR, Underwood D (1994) Structure and function of G protein-coupled receptors. Annu Rev Biochem 63: 101–132

    PubMed  CAS  Google Scholar 

  • Strittmatter WJ, Roses AD (1995) Apolipoprotein E and Alzheimer’s disease. Proc Natl Acad Sci USA 92: 4725–4727

    PubMed  CAS  Google Scholar 

  • Tecott L, Sun LM, Akana SF, Strack AM, Lowenstein DH, Dallman MF, Julius D (1995) Eating disorder and epilepsy in mice lacking 5-HT2C serotonin receptors. Nature 374: 542–546

    PubMed  CAS  Google Scholar 

  • Teitler M, Leonhardt S, Weisberg EL, Hoffman BJ (1990) 4-[125]Iodo- (2,5-dimethoxy)phenylisopropylamine and [3H]ketanserin labeling of 5- hydroxytryptamine2 (5-HT2) receptors in mammalian cells transfected with a rat 5-HT, cDNA: evidence for multiple states and not multiple 5-HT2 receptor subtypes. Mol Pharmacol 38: 594–598

    PubMed  CAS  Google Scholar 

  • Tsou AT, Kosaka A, Bach C, Zuppan P, Yee C, Tom L, Alvarez R, Ramsey S, Bonhaus DW, Stefanich E, et. al. (1994) Cloning and expression of a 5-hydroxytryptamine7 receptor positively coupled to adenylyl cyclase. J Neurochem 63: 456–464

    PubMed  CAS  Google Scholar 

  • van Huizen F, Bansse MT, Stam NJ (1993) Agonist-induced down-regulation of human 5-HT1A and 5-HT2 receptors in Swiss 3T3 cells. Neuroreport 4: 1327–1330

    PubMed  Google Scholar 

  • Van Obberghen-Schilling E, Vouret-Craviari V, Haslam RJ, Chambard J-C, Pouyssgur (1991) Cloning, functional expression and role in cell growth regulation of a hamster 5-HT2 receptor subtype. Mol Endocrinol 5: 881–889

    PubMed  Google Scholar 

  • Varrault A, Le Nguyen D, McClue S, Harris B, Jouin P, Bockaert J (1994) 5- Hydroxytryptamine1Areceptor synthetic peptides. Mechanisms of adenylyl cyclase inhibition. J Biol Chem 269: 16720–16725

    PubMed  CAS  Google Scholar 

  • Veldman SA, Bienkowski MJ (1992) Cloning and pharmacological characterization of a novel human 5-hydroxytryptamine1D receptor subtype. Mol Pharmacol 42: 439–444

    PubMed  CAS  Google Scholar 

  • Voigt MM, Laurie DJ, Seeburg PH, Bach A (1991) Molecular cloning and characterization of a rat brain cDNA encoding a 5-hydroxytryptamine1B receptor. EMBO J 10: 4017–4023

    PubMed  CAS  Google Scholar 

  • Wahlestedt C (1994) Antisense oligonucleotide strategies in neuropharmacology. Trends Pharmacol Sci 15: 42–46

    PubMed  CAS  Google Scholar 

  • Wainscott DB, Cohen ML, Schenck KW, Audia JE, Nissen JS, Baez M, Kursar JD, Lucaites VL, Nelson DL (1993) Pharmacological characteristics of the newly cloned rat 5-hydroxytryptamine2F receptor. Mol Pharmacol 43: 419–426

    PubMed  CAS  Google Scholar 

  • Weinshank RL, Zgombick JM, Macchi MJ, Branchek TA, Hartig PR (1992) Human serotonin1D receptor is encoded by a subfamily of two distinct genes: 5HT1Dα and 5-HT1Dβ.Proc Natl Acad Sci USA 89: 3630–3634

    PubMed  CAS  Google Scholar 

  • Wills C (1993) The runaway brain. Basic Books, New York

    Google Scholar 

  • Wisden W, Parker EM, Mahle CD, Grisel DA, Nowak HP, Yocca FD, Felder CC, Seeburg PH, Voigt MM (1993) Cloning and characterization of the rat 5-HT5B receptor: evidence that the 5-HT5B receptor couples to a G protein in mammalian cell membranes. FEBS Lett 33: 25–31

    Google Scholar 

  • Witz P, Amlaiky N, Plassat JL, Maroteaux L, Borelli E, Hen R (1990) Cloning and characterization of a Drosophila serotonin receptor that activates adenylate cyclase. Proc Natl Acad Sci USA 87: 8940–8944

    PubMed  CAS  Google Scholar 

  • Yocca FD, Iben L, Meller E (1992) Lack of apparent receptor reserve at postsynaptic 5-hydroxytryptamine1A receptors negatively coupled to adenylyl cyclase activity in rat hippocampal membranes. Mol Pharmacol 41: 1066–1072

    PubMed  CAS  Google Scholar 

  • Yu L, Nguyen H, Le H, Bloem LJ, Kozak CA, Hoffman BJ, Snutch TP, Lester HA, Davidson N, Lübbert H (1991) The mouse 5-HT1C receptor contains eight hydrophobic domains and is X-linked. Mol Brain Res II: 143–149

    Google Scholar 

  • Zgombick JM, Weinshank RL, Macchi M, Schecher LE, Branchek TA, Hartig PR (1991) Expression and pharmacological characterization of a canine 5- hydroxytryptamine1D receptor subtype. Mol Pharmacol 40: 1036–1042

    PubMed  CAS  Google Scholar 

  • Zgombick JM, Schechter LE, Macchi M, Hartig PR, Branchek TA, Weinshank RL (1992) Human gene S31 encodes the pharmacologically defined serotonin 5- hydroxyptamine1E receptor. Mol Pharmacol 42: 180–185

    PubMed  CAS  Google Scholar 

  • Zgombick JM, Borden LA, Cochran TL, Kucharewicz SA, Weinshank RL, Branchek TA (1993) Dual coupling of cloned human 5-hydroxytryptamine1Dα and 5- hydroxytryptamine1Dß receptors stably expressed in murine fibroblasts: inhibition of adenylate cyclase and elevation of intracellular calcium concentrations via pertussis toxin-sensitive G proteins. Mol Pharmacol 44: 575–582

    PubMed  CAS  Google Scholar 

  • Zhu QS, Chen K, Shih JC (1995) Characterization of the human 5-HT2A receptor gene promoter. J Neurosci 15(7Pt1): 4885–4895

    PubMed  CAS  Google Scholar 

Download references

Authors

Editor information

Editors and Affiliations

Rights and permissions

Reprints and permissions

Copyright information

© 2000 Springer-Verlag Berlin Heidelberg

About this chapter

Cite this chapter

Hartig, P.R. (2000). Molecular Biology and Transductional Characteristics of 5-HT Receptors. In: Baumgarten, H.G., Göthert, M. (eds) Serotoninergic Neurons and 5-HT Receptors in the CNS. Handbook of Experimental Pharmacology, vol 129. Springer, Berlin, Heidelberg. https://doi.org/10.1007/978-3-642-60921-3_7

Download citation

  • DOI: https://doi.org/10.1007/978-3-642-60921-3_7

  • Publisher Name: Springer, Berlin, Heidelberg

  • Print ISBN: 978-3-540-66715-5

  • Online ISBN: 978-3-642-60921-3

  • eBook Packages: Springer Book Archive

Publish with us

Policies and ethics