Selective blocking effects of tropisetron and atropine on recombinant glycine receptors

Gábor Maksay, Bodo Laube, Heinrich Betz

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30 Citations (Scopus)

Abstract

Some serotonin 5-HT3 receptor ligands of tropeine structure have been recently shown to modulate ionophore function and binding of glycine receptors. This led us to study the effects of the tropeines tropisetron and atropine on recombinant human glycine receptors transiently expressed in Xenopus oocytes by using whole-cell voltage-clamp electrophysiology. Glycine currents were inhibited by atropine in an apparently competitive manner and with considerable selectivity of the tropeines for α2 versus α1 subunits. Coexpression of β with subunits and replacement of the N-terminal region of the α1 subunits by the corresponding β segment resulted in similar increases in the inhibitory potencies. Our data suggest common sites of the tropeines for inhibition on the N-terminal region of glycine receptors. The point mutations R271K and R271L of the α1 subunit decreased, whereas a T112A substitution increased, the inhibition constants (K(i)) of the tropeines. These changes in the K(i) values of the tropeines were associated with opposite changes in the EC50 of glycine. Selectivities for the tropeines versus glycine (EC50/K(i)) varied within three orders of magnitude. These results, when expressed in terms of free energy changes, can be interpreted according to a two-state receptor model.

Original languageEnglish
Pages (from-to)802-806
Number of pages5
JournalJournal of neurochemistry
Volume73
Issue number2
DOIs
Publication statusPublished - Jul 29 1999

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Keywords

  • Atropine
  • Chloride ionophore
  • Free energy correlation of gating
  • Recombinant glycine receptors
  • Tropisetron

ASJC Scopus subject areas

  • Biochemistry
  • Cellular and Molecular Neuroscience

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