Cloning, characterization, and chromosomal localization of a human 5-HT6 serotonin receptor

Ruth Kohen, Mark A. Metcalf, Naseem Khan, Teresa Druck, Kay Huebner, Jean E. Lachowicz, Herbert Y. Meltzer, David R. Sibley, Bryan L. Roth, Mark W. Hamblin*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

343 Scopus citations

Abstract

We describe the cloning and characterization of a human 5-HT6 serotonin receptor. The open reading frame is interrupted by two introns in positions corresponding to the third cytoplasmic loop and the third extracellular loop. The human 5-HT6 cDNA encodes a 440-amino-acid polypeptide whose sequence diverges significantly from that published for the rat 5-HT6 receptor. Resequencing of the rat cDNA revealed a sequencing error producing a frame shift within the open reading frame. The human 5-HT6 amino acid sequence is 89% similar to the corrected rat sequence. The recombinant human 5-HT6 receptor is positively coupled to adenylyl cyclase and has pharmacological properties similar to the rat receptor with high affinity for several typical and atypical antipsychotics, including clozapine. The receptor is expressed in several human brain regions, most prominently in the caudate nucleus. The gene for the receptor maps to the human chromosome region 1p35-p36. This localization overlaps that established for the serotonin 5-HT(1Dα) receptor, suggesting that these may be closely linked. Comparison of genomic and cDNA clones for the human 5-HT6 receptor also reveals an Rsal restriction fragment length polymorphism within the coding region.

Original languageEnglish (US)
Pages (from-to)47-56
Number of pages10
JournalJournal of neurochemistry
Volume66
Issue number1
DOIs
StatePublished - Jan 1996

Keywords

  • Atypical antipsychotics
  • Chromosomal localization
  • Clozapine
  • G protein-coupled receptors
  • Serotonin receptors

ASJC Scopus subject areas

  • Biochemistry
  • Cellular and Molecular Neuroscience

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