Allosteric modulation of glycine receptors is more efficacious for partial rather than full agonists

Tímea Bíró, Gábor Maksay

Research output: Contribution to journalArticle

7 Citations (Scopus)

Abstract

Allosteric modulation of [3H]strychnine binding to glycine receptors (GlyRs) was examined in synaptosomal membranes of rat spinal cord. An allosteric model enabled us to determine the cooperativity factors of the allosteric agents with [3H]strychnine and glycine bindings (α and β, respectively). We modified the allosteric model with a slope factor because the slope values of the displacement curves of partial agonists (β-alanine, taurine and γ-aminobutyric acid) were beyond unity. The slope factor was reduced only by 100μM propofol. Further, propofol showed positive cooperativity (β<1) stronger with taurine than with glycine. The extent of the positive cooperativity of propofol was nearly independent from the potencies and structures of partial agonists. The steroidal alphaxalone and minaxolone also potentiated taurine better than glycine. Alphaxalone exerted weak negative cooperativity with [3H]strychnine binding. Displacement by taurine is attenuated by granisetron and m-chlorophenylbiguanide representing negative cooperativity (β≫1) greater than with glycine. The results suggest a developmental role of elevated perinatal levels of taurine and neurosteroids as well as a better allosteric modulation of decreased agonist efficacies for impaired glycine receptor-ionophores.

Original languageEnglish
Pages (from-to)521-527
Number of pages7
JournalNeurochemistry international
Volume44
Issue number7
DOIs
Publication statusPublished - Jun 2004

Keywords

  • Allosteric model
  • Glycine receptor
  • Partial agonists
  • Propofol
  • Taurine
  • [H]strychnine binding

ASJC Scopus subject areas

  • Cellular and Molecular Neuroscience
  • Cell Biology

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