Differentiation of glycine antagonist sites of N-methyl-D-aspartate receptor subtypes. Preferential interaction of CGP 61594 with NR1/2B receptors.

The Journal of Biological Chemistry
M HonerH Mohler

Abstract

The binding site for the co-agonist glycine on N-methyl-D-aspartate (NMDA) receptors has been mapped to the NR1 subunit whereas binding of the principal agonist glutamate is mediated by the NR2 subunits. Using the novel glycine site antagonist and photoaffinity label CGP 61594, distinct contributions of the NR2 subunit variants to the glycine antagonist binding domains of NMDA receptor subtypes are demonstrated. High affinity sites for CGP 61594 were exclusively displayed by NR1/2B receptors, as shown by their co-distribution with the NR2B subunit, by subunit-selective immunoprecipitation and by functional analysis of NR1/2B receptors expressed in Xenopus oocytes (inhibitory potency, IC50 = 45 +/- 11 nM). Other NMDA receptor subtypes are clearly distinguished by reduced inhibitory potencies for CGP 61594, being low for NR1/2A and NR1/2D receptors (IC50 = 430 +/- 105 nM and 340 +/- 61 nM, respectively) and intermediate for NR1/2C receptors (IC50 = 164 +/- 27 nM). Glycine antagonist sites with low and intermediate affinity for [3H]CGP 61594 were detected also in situ by radioligand binding in brain areas predominantly expressing the NR2A and NR2C subunits, respectively. Thus, [3H]CGP 61594 is the first antagonist radioligand that...Continue Reading

References

Jul 2, 1992·Nature·T KutsuwadaM Arakawa
Nov 7, 1991·Nature·K MoriyoshiS Nakanishi
Aug 1, 1990·Trends in Pharmacological Sciences·R DingledineJ O McNamara
Aug 1, 1987·Molecular and Cellular Biology·C Chen, H Okayama
Nov 1, 1985·Journal of Pharmacological Methods·G A McPherson
Dec 1, 1995·Archives of General Psychiatry·J W Olney, N B Farber
May 22, 1994·The Journal of Comparative Neurology·M WatanabeY Inoue
May 22, 1994·The Journal of Comparative Neurology·M WatanabeY Inoue
Aug 16, 1994·European Journal of Pharmacology·D J Laurie, P H Seeburg
Jan 1, 1994·Progress in Brain Research·D W Choi
May 1, 1994·The Journal of Comparative Neurology·D G StandaertJ B Penney
Dec 15, 1993·The Journal of Comparative Neurology·M WatanabeM Mishina
Jan 1, 1994·Annual Review of Neuroscience·M Hollmann, S Heinemann
Jan 1, 1993·Trends in Pharmacological Sciences·J A Kemp, P D Leeson
Oct 1, 1995·Neuropharmacology·H Mori, M Mishina
Jun 28, 1996·The Journal of Biological Chemistry·J Blahos, R J Wenthold
Jan 1, 1995·Journal of Receptor and Signal Transduction Research·D BenkeH Mohler
Oct 1, 1996·Trends in Pharmacological Sciences·N J SucherS A Lipton

❮ Previous
Next ❯

Citations

Apr 6, 2001·European Journal of Pharmacology·D R LynchR P Guttmann
Dec 14, 2002·Brain Research. Developmental Brain Research·Christopher D ToscanoTomás R Guilarte
Mar 30, 1999·Brain Research. Molecular Brain Research·M K Nihei, T R Guilarte
Nov 6, 2009·Journal of Computer-aided Molecular Design·Bjoern A KruegerGisbert Schneider
Jan 5, 2001·Expert Opinion on Investigational Drugs·M E Tranquillini, A Reggiani
May 28, 2004·Pharmacology & Therapeutics·Penelope J Hallett, David G Standaert
Dec 18, 1998·Neuron·J P Changeux, S J Edelstein
Nov 5, 2005·Brain Research. Brain Research Reviews·Christopher D Toscano, Tomás R Guilarte

❮ Previous
Next ❯

Related Concepts

Related Feeds

ASBMB Publications

The American Society for Biochemistry and Molecular Biology (ASBMB) includes the Journal of Biological Chemistry, Molecular & Cellular Proteomics, and the Journal of Lipid Research. Discover the latest research from ASBMB here.