TU Darmstadt / ULB / TUbiblio

Hyperekplexia mutation R271L of alpha1 glycine receptors potentiates allosteric interactions of nortropeines, propofol and glycine with [3H]strychnine binding.

Maksay, Gábor and Bíró, Tímea and Laube, Bodo and Nemes, Péter (2008):
Hyperekplexia mutation R271L of alpha1 glycine receptors potentiates allosteric interactions of nortropeines, propofol and glycine with [3H]strychnine binding.
In: Neurochemistry international, pp. 235-40, 52, (1-2), ISSN 0197-0186, [Article]

Abstract

Human alpha1 and hyperekplexia mutant alpha1(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 beta was 0.26 for alpha1 GlyRs and 0.04 for alpha1(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.

Item Type: Article
Erschienen: 2008
Creators: Maksay, Gábor and Bíró, Tímea and Laube, Bodo and Nemes, Péter
Title: Hyperekplexia mutation R271L of alpha1 glycine receptors potentiates allosteric interactions of nortropeines, propofol and glycine with [3H]strychnine binding.
Language: English
Abstract:

Human alpha1 and hyperekplexia mutant alpha1(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 beta was 0.26 for alpha1 GlyRs and 0.04 for alpha1(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.

Journal or Publication Title: Neurochemistry international
Volume: 52
Number: 1-2
Divisions: 10 Department of Biology
10 Department of Biology > Neurophysiology and Neurosensory Systems
?? fb10_zoologie ??
Date Deposited: 11 Apr 2011 09:25
Export:

Optionen (nur für Redakteure)

View Item View Item