Allosteric modulation of [3H]-CGP39653 binding through the glycine site of the NMDA receptor: further studies in the rat and human brain

M Mugnaini, P Meoni, B Bunnemann, M Corsi, Norman Bowery

Research output: Contribution to journalArticle

7 Citations (Scopus)

Abstract

Binding of D,L-(E)-2-amino-4-[(3)H]-propyl-5-phosphono-3-pentenoic acid ([(3)H]-CGP39653), a selective antagonist at the glutamate site of the NMDA receptor, is modulated by glycine in rat brain tissue. We have further investigated this phenomenon in rodent and human brain by means of receptor binding and quantitative autoradiography techniques. In rat cerebral cortical membranes the glycine antagonist 3-[2-(Phenylaminocarbonyl)ethenyl]-4,6-dichloro-indole-2-carboxylic acid sodium salt (GV150526A) did not change basal [(3)H]-CGP39653 binding, but competitively reversed the high affinity component of [(3)H]-CGP39653 binding inhibition by glycine, with a pK(B) value of 8.38, in line with its affinity for the glycine site (pK(i)=8.49 vs. [(3)H]-glycine). Glycine (10 microM) significantly decreased [(3)H]-CGP39653 affinity for the NMDA receptor (with no change in the B(max)), whereas enhanced L-glutamate affinity (P
Original languageEnglish
Pages (from-to)1883-1897
Number of pages15
JournalBritish Journal of Pharmacology
Volume132
DOIs
Publication statusPublished - 1 Apr 2001

Keywords

  • human brain
  • allosteric modulation
  • glycine
  • GV150526A
  • CGP39653
  • NMDA receptor
  • receptor binding
  • glutamate
  • autoradiography

Fingerprint

Dive into the research topics of 'Allosteric modulation of [3H]-CGP39653 binding through the glycine site of the NMDA receptor: further studies in the rat and human brain'. Together they form a unique fingerprint.

Cite this