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

https://doi.org/10.1016/0006-291X(92)90654-4Get rights and content

Abstract

We describe a genomic clone encoding the human 5-HT1B receptor. This apparently intronless gene encodes a 390 amino acid polypeptide homologous to the rat 5-HT1B serotonin receptor, with which it shares 93% amino acid sequence identity. Remarkably, [3H]5-hydroxytryptamine binding studies with transfected HeLa cells show that the human 5-HT1B receptor has a pharmacological profile that is markedly different from that of the corresponding rat receptor. Instead, human 5-HT1B drug specificity is highly similar to that of the human 5-HT1D receptor, with which it shares 59% amino acid sequence identity. The human 5-HT1B receptor, like the 5-HT1D receptor, can couple to Gi proteins. The presence of the threonine355 in the human receptor rather than an asparagine, as found in the corresponding rat gene product, may explain much of the marked pharmacological difference between the human and rat 5-HT1B receptors.

References (33)

  • D. Hoyer et al.

    Eur. J. Pharmacol

    (1985)
  • R. Bouhelal et al.

    Eur. J. Pharmacol

    (1988)
  • G. Maura et al.

    Eur. J. Pharmacol

    (1986)
  • R.E. Heuring et al.

    Eur. J. Pharmacol

    (1986)
  • D. Hoyer et al.

    Trends Pharmacol. Sci

    (1989)
  • P.J. Munson et al.

    Anal. Biochem

    (1980)
  • M.M. Bradford

    Anal. Biochem

    (1976)
  • B.F. O'Dowd et al.

    J. Biol. Chem

    (1989)
  • A. Pazos et al.

    Brain Res

    (1985)
  • S. Suryanarayana et al.

    J. Biol. Chem

    (1991)
  • J. Kyte et al.

    J. Mol. Biol

    (1982)
  • G. Engel et al.

    Naunyn-Schmiedeberg's Arch. Pharmacol

    (1986)
  • D.N. Middlemiss

    J. Pharm. Pharmacol

    (1985)
  • G. Maura et al.

    Naunyn-Schmiedeberg's Arch. Pharmacol

    (1986)
  • S.J. Offord et al.

    J. Pharm. Exp. Ther

    (1988)
  • P.B. Crino et al.

    J. Pharmacol. Exp. Ther

    (1990)
  • Cited by (111)

    • Serotonin receptors nomenclature

      2019, The Serotonin System: History, Neuropharmacology, and Pathology
    • Role of the serotonergic system in alcohol dependence: From animal models to clinics

      2011, Progress in Molecular Biology and Translational Science
      Citation Excerpt :

      Understanding the pharmacology of 5-HT1B receptors is an important step in determining the physiological role of these receptors. Pharmacological studies have demonstrated that RU 24969 and trifluoromethyl-phenylpiperazine possess high affinity for 5-HT1B receptor binding sites in rodents, and that serotonergic agonist 5-CT has high affinity for both 5-HT1D and 5-HT1B receptor binding sites.153–155 Another agonist, CP 93129, demonstrates stronger affinity for 5-HT1B receptor binding sites over 5-HT1D receptors,156 whereas sumatriptan has a higher affinity for 5-HT1D receptor binding than for 5-HT1B receptors.28,157

    • Genetic Organization of the Serotonergic System

      2010, Handbook of Behavioral Neuroscience
    View all citing articles on Scopus

    Sequence data from this article have been deposited with the EMBL/GenBank Data Libraries under Accession No. M89478.

    View full text