Cloning of the choroid plexus 5-HT1C receptor

  • Paul R. Hartig
Part of the Developments in CardioCardiovascular Pharmacology of 5-Hydroxytryptamine book series (DICM, volume 106)


In the limited time that molecular cloning techniques have been successfully applied to neurotransmitter receptors, we have learned of strong sequence homologies among one group of receptors, the G protein-coupled receptors, that unite these proteins into one structural family [1]. Members of this family include the muscarinic cholinoceptors, alpha- and beta-adrenoceptors, opsin and the Substance K receptor [1, 2]. All members of this family are single subunit proteins containing seven membrane-spanning domains with interconnecting extracellular and cytoplasmic sequences. The transmembrane domains exhibit strong sequence homologies among the family members, while the interconnecting water soluble domains are less well conserved. Recently, the 5-HT1C receptor became the first serotonergic member of this family of cloned G-protein-coupled receptors, and so became the first 5-hydroxytryptamine (5-HT) receptor subtype to be understood at the amino acid sequence level [3, 4]. The strategy used to clone the 5-HT1C receptor is a powerful new approach to molecular cloning, which will be broadly applicable to many receptor and ion channel proteins. The basics of this strategy will be reviewed in this chapter, along with information it has provided on the structure of the 5-HT1C receptor.


Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.


  1. 1.
    Dohlman HG, Caron MG, Lefkowitz RJ (1987): A family of receptors coupled to guanine nucleotide regulatory proteins, Biochemistry26: 2657–2664.PubMedCrossRefGoogle Scholar
  2. 2.
    Lester HA (1988): Heterologous expression of excitability proteins: route to more specific drugs? Science241: 1057–1063.PubMedCrossRefGoogle Scholar
  3. 3.
    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 using electrophysiological assays of mRNA-injected Xenopus oocytes. Proc Natl Acad Sci USA 84:4332–4336.PubMedCrossRefGoogle Scholar
  4. 4.
    Julius D, MacDermott AB, Axel R, Jessell TM (1988): Molecular characterization of a functional cDNA encoding the serotonin 5-HT1c receptor. Science241: 558–564.PubMedCrossRefGoogle Scholar
  5. 5.
    Gundersen CB, Miledi R, Parker I (1983): Serotonin receptors induced by exogenous messenger RNA in Xenopus oocytes. Proc Royal Soc LondonB219: 103–109.CrossRefGoogle Scholar
  6. 6.
    Dascal N, Ifune C, Hopkins R, Snutch TP, Lübbert H, Davidson N, Simon MI, Lester HA (1986): Involvement of a GTP-binding protein in mediation of serotonin and acetylcholine responses in Xenopus oocytes injected with rat brain messenger RNA Mol Brain Res1: 201–209.CrossRefGoogle Scholar
  7. 7.
    Lübbert H, Snutch TP, Dascal N, Lester HA, Davidson N (1987): Rat brain 5-HT1c receptors are encoded by a 5–6 kbase mRNA size class and are functionally expressed in injected Xenopus oocytes.J Neurosci7: 1159–1165.Google Scholar
  8. 8.
    Yagaloff KA, Lozano G, van Dyke T, Levine AJ, Hartig PR (1986): Serotonin 5-HT1c receptors are expressed at high density on choroid plexus tumors from transgenic mice. Brain Res385: 389–394.PubMedCrossRefGoogle Scholar
  9. 9.
    Hoffman BJ (1988): Molecular pharmacology of serotonin receptors: radioligand development, mechanisms of signal transduction, and cloning of a receptor gene. Doctoral thesis, Johns Hopkins University.Google Scholar
  10. 10.
    Sutcliffe JG (1988): mRNA in the mammalian central nervous system. Ann Rev Neurosci 11:157–198.PubMedCrossRefGoogle Scholar
  11. 11.
    Dixon RAF, Sigal IS, Rands E, Register RB, Candelore MR, Blake AD, Strader CD (1987): Ligand binding to the beta-adrenergic receptor involves its rhodopsin-like core, Nature326: 73–77.PubMedCrossRefGoogle Scholar
  12. 12.
    Dixon RAF, Sigal IS, Candelore MR, Register RB, Scattergood W, Rands E, Strader CD (1987): Structural features required for ligand binding to the beta-adrenergic receptor, EMBO Journal6: 3269–3275.PubMedGoogle Scholar
  13. 13.
    Kobilka BK, Kobilka TS, Daniel K, Regan JW, Caron MG, Lefkowitz RJ (1988): Chimeric alpha2-, beta2-adrenergic receptors: delineation of domains involved in effector coupling and ligand binding specificity, Science240: 1310–1316.PubMedCrossRefGoogle Scholar
  14. 14.
    Strader CD, Sigal IS, Register RB, Candelore MR, Rands E, Dixon RAF (1987): Identification of residues required for ligand binding to the beta-adrenergic receptor, Proc Natl Acad Sci USA84: 4384–4388.PubMedCrossRefGoogle Scholar
  15. 15.
    Hoyer D (1988): Moleuclar pharmacology and biology of 5-HT1c receptors, Trends Pharm Sci9: 89–94.PubMedCrossRefGoogle Scholar
  16. 16.
    Peroutka SJ (1988): 5-Hydroxytryptamine Receptor Subtypes, Ann Rev Neurosci 11: 45–60.PubMedCrossRefGoogle Scholar
  17. 17.
    Hartig PR (1989): Molecular biology of 5-HT receptors. Trends Pharm Sci10: 64–69.PubMedCrossRefGoogle Scholar

Copyright information

© Springer Science+Business Media Dordrecht 1990

Authors and Affiliations

  • Paul R. Hartig

There are no affiliations available

Personalised recommendations