Differential stimulation of [3H]MK-801 binding to subpopulations of NMDA receptors

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Abstract

The potency of l-glutamate in enhancing [3H]MK-801 binding to N-methyl-d-aspartate (NMDA) receptor ion channels was evaluated by quantitative autoradiography. In the presence of saturating concentrations of spermine, glycine and 20 μM d-2-amino-5-phosphonopentanoate (d-AP5), low concentrations of l-glutamate selectively increased [3H]MK-801 binding in the medial striatum and dorsal lateral septum. In comparison to these regions, EC50 values for l-glutamate stimulation of [3H]MK-801 binding were significantly higher in the cerebral cortex and thalamus. Regions displaying greater sensitivity to l-glutamate correlate to those regions where NMDA receptors are preferentially labelled by l-[3H]glutamate; regions less sensitive to l-glutamate correspond to regions selectively labelled by the NMDA antagonist [3H]CPP ([3H]3-((+)-2-carboxypiperazin-4-yl)-propyl-1-phosphonate). Since l-glutamate stimulation of [3H]MK-801 binding appears to reflect channel activation, these results suggest that it is possible to pharmacologically (or pathologically) activate anatomically-distinct subpopulations of NMDA receptors.

Original languageEnglish (US)
Pages (from-to)21-24
Number of pages4
JournalNeuroscience Letters
Volume122
Issue number1
DOIs
StatePublished - Jan 14 1991

Keywords

  • Autoradiography
  • Excitatory amino acid
  • Glycine
  • MK-801
  • NMDA receptor
  • Polyamine

ASJC Scopus subject areas

  • Neuroscience(all)

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