3H-labeled MK-801 binding to the excitatory amino acid receptor complex from rat brain is enhanced by glycine.
- 1 November 1987
- journal article
- research article
- Published by Proceedings of the National Academy of Sciences in Proceedings of the National Academy of Sciences
- Vol. 84 (21) , 7744-7748
- https://doi.org/10.1073/pnas.84.21.7744
Abstract
We have studied the binding of the excitatory amino acid antagonist 3H-labeled MK-801 [(+)-5-methyl-10,11-dihydro-5H-dibenzo[a,d]cyclohept-5,10-imine maleate] to extensively washed rat brain membranes. Binding of 3H-labeled MK-801 was inhibited by phencyclidine, Mg2+, and 3-(2-carboxypiperazin-4-yl)-propyl-1-phosphonic acid in a manner dependent on the presence of L-glutamate or N-methyl-D-aspartate, suggesting that it labeled a site linked to the N-methyl-D-aspartate subtype of the glutamate receptor. Glycine also regulated 3H-labeled MK-801 binding, enhancing it in the concentration range of 0.01-10 .mu.M. The actions of glutamate and glycine involved increases in binding affinity, without altering the number of 3H-labeled MK-801 binding sites. The effects of glycine in this system were mimicked by L- and D-alanine and L- and D-serine. However, .beta.-alanine and taurine were much less effective, and strychnine did not block the actions of glycine indicating that they were not mediated by the classical glycine receptors. Glycine also enhanced the ability of N-methyl-D-aspartate to increase Ca2+ influx into primary cultures of mouse striatal neurons measured using the Ca2+-sensitive fluorescent dye fura-2. These results support the suggestion that glycine may be an important regulator of the physiological actions of glutamate in vivo.This publication has 22 references indexed in Scilit:
- The novel anticonvulsant MK-801 interacts with central phencyclidine recognition sites in rat brainEuropean Journal of Pharmacology, 1987
- Glycine potentiates the NMDA response in cultured mouse brain neuronsNature, 1987
- The physiology of excitatory amino acids in the vertebrate central nervous systemProgress in Neurobiology, 1987
- [3H]CPP, a new competitive ligand for NMDA receptorsEuropean Journal of Pharmacology, 1986
- CPP, a new potent and selective NMDA antagonist. Depression of central neuron responses, affinity for [3H]d-AP5 binding sites on brain membranes and anticonvulsant activityBrain Research, 1986
- Light microscopic autoradiographic localisation of [3H]glycine and [3H]strychnine binding sites in rat brainEuropean Journal of Pharmacology, 1986
- Acidic amino acid binding sites in mammalian neuronal membranes: their characteristics and relationship to synaptic receptorsBrain Research Reviews, 1984
- Magnesium gates glutamate-activated channels in mouse central neuronesNature, 1984
- A practical computer-based approach to the analysis of radioligand binding experimentsComputer Programs in Biomedicine, 1983
- GABA‐Benzodiazepine‐Barbiturate Receptor InteractionsJournal of Neurochemistry, 1981