RT Journal Article
SR Electronic
T1 Up-regulation of N-methyl-D-aspartate receptors on cultured cortical neurons after exposure to antagonists.
JF Molecular Pharmacology
JO Mol Pharmacol
FD American Society for Pharmacology and Experimental Therapeutics
SP 147
OP 151
VO 42
IS 1
A1 K Williams
A1 M A Dichter
A1 P B Molinoff
YR 1992
UL http://molpharm.aspetjournals.org/content/42/1/147.abstract
AB The density of N-methyl-D-aspartate (NMDA) receptors on membranes prepared from cultured cortical neurons was determined using binding assays with [125I]I-MK-801 after exposure of cultures to antagonists of the NMDA receptor complex. The density of binding sites for [125I]I-MK-801 was increased by 40-80% after exposure to D-2-amino-5-phosphonopentanoic acid (D-AP5), with no change in the number or viability of neurons. The effect of D-AP5 was concentration dependent, with an EC50 of 10 microM. Up-regulation of NMDA receptors was observed after 2-7 days but not after 1 day of exposure to 100 microM D-AP5. The density of NMDA receptors was also increased after exposure of cells to CGS 19755 and MK-801 but not after exposure to the alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA)/kainate receptor antagonist 6-cyano-7-nitroquinoxaline-2,3-dione. The binding of [3H]AMPA was unaltered after exposure to D-AP5. These results demonstrate that the density of NMDA receptors on cultured neurons can be selectively up-regulated by exposure to NMDA receptor antagonists. Increases in the density of NMDA receptors occurring in vivo could complicate therapeutic approaches to the treatment of neurological disorders.