Evidence for expression of heteromeric serotonin 5-HT(3) receptors in rodents

M C Hanna, P A Davies, T G Hales, E F Kirkness

Research output: Contribution to journalArticlepeer-review

81 Citations (Scopus)

Abstract

The gene and cDNAs that encode a novel subunit of rodent serotonin 5-HT(3) receptors were isolated from mouse and rat tissues. Each of the new rodent subunits shares 40% amino acid identity with the rat 5-HT(3A) subunit and 73% identity with the human 5-HT(3B) subunit. Despite a relatively low level of structural conservation, sequence analysis and functional studies suggest that the new rodent subunits are orthologues of the human 5-HT(3B) subunit. In common with homologous human receptors, rat heteromeric 5-HT(3) receptors displayed a substantially larger single-channel conductance than homomeric 5-HT(3A) receptors. In addition, the rat heteromeric receptors were less sensitive to antagonism by tubocurarine. However, in contrast to human heteromeric receptors, those of the rat displayed pronounced inward rectification of both the whole-cell and single-channel current amplitudes. Transcripts of the mouse 5-HT(3A) and 5-HT(3B) subunits are coexpressed in several cell lines that possess endogenous 5-HT(3) receptors. In addition, treatment of rat PC12 cells with nerve growth factor induced expression of both subunit mRNAs, with a similar time course for accumulation of each transcript. The combination of functional data and expression patterns is consistent with the existence of heteromeric 5-HT(3) receptors in rodent neurons.

Original languageEnglish
Pages (from-to)240-7
Number of pages8
JournalJournal of Neurochemistry
Volume75
Issue number1
DOIs
Publication statusPublished - Jul 2000

Keywords

  • Amino Acid Sequence
  • Animals
  • Cloning, Molecular
  • DNA, Complementary
  • Electric Conductivity
  • Gene Expression
  • Humans
  • Macromolecular Substances
  • Mice
  • Molecular Sequence Data
  • PC12 Cells
  • RNA, Messenger/analysis
  • Rats
  • Receptors, Serotonin/chemistry
  • Receptors, Serotonin, 5-HT3
  • Recombinant Proteins/metabolism
  • Sequence Homology

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