Hyperekplexia mutation R271L of α1 glycine receptors potentiates allosteric interactions of nortropeines, propofol and glycine with [3H]strychnine binding

Gábor Maksay, Tímea Bíró, Bodo Laube, Péter Nemes

Research output: Contribution to journalArticle

6 Citations (Scopus)

Abstract

Human α1 and hyperekplexia mutant α1(R271L) glycine receptors (GlyRs) were transiently expressed in human embryonic kidney 293 cells for [3H]strychnine binding. Binding parameters were determined using a ternary allosteric model. The hyperekplexia mutation increased the positive cooperativity of 0.3 mM propofol and glycine binding by about six times: the cooperativity factor β was 0.26 for α1 GlyRs and 0.04 for α1(R271L) GlyRs. Thus, propofol restored the potency of glycine impaired by the mutation. Five nortropeines, i.e. substituted benzoates of nortropine and a new compound, nortropisetron were prepared and also examined on [3H]strychnine binding. They showed nanomolar displacing potencies amplified by the hyperekplexia mutation. The affinity of nor-O-zatosetron (2.6 nM) is one of the highest reported for GlyRs. This binding test offers an in vitro method to evaluate agents against neurological disorders associated with inherited mutations of GlyRs.

Original languageEnglish
Pages (from-to)235-240
Number of pages6
JournalNeurochemistry international
Volume52
Issue number1
DOIs
Publication statusPublished - Jan 1 2008

Keywords

  • Hyperekplexia mutation
  • Propofol
  • Recombinant α glycine receptors
  • Ternary allosteric model
  • Tropeines
  • [H]strychnine binding

ASJC Scopus subject areas

  • Cellular and Molecular Neuroscience
  • Cell Biology

Fingerprint Dive into the research topics of 'Hyperekplexia mutation R271L of α<sub>1</sub> glycine receptors potentiates allosteric interactions of nortropeines, propofol and glycine with [<sup>3</sup>H]strychnine binding'. Together they form a unique fingerprint.

  • Cite this