Tags

Type your tag names separated by a space and hit enter

Up-regulation of N-methyl-D-aspartate receptors on cultured cortical neurons after exposure to antagonists.
Mol Pharmacol. 1992 Jul; 42(1):147-51.MP

Abstract

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.

Authors+Show Affiliations

Department of Pharmacology, University of Pennsylvania School of Medicine, Philadelphia 19104-6084.No affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't
Research Support, U.S. Gov't, P.H.S.

Language

eng

PubMed ID

1353248

Citation

Williams, K, et al. "Up-regulation of N-methyl-D-aspartate Receptors On Cultured Cortical Neurons After Exposure to Antagonists." Molecular Pharmacology, vol. 42, no. 1, 1992, pp. 147-51.
Williams K, Dichter MA, Molinoff PB. Up-regulation of N-methyl-D-aspartate receptors on cultured cortical neurons after exposure to antagonists. Mol Pharmacol. 1992;42(1):147-51.
Williams, K., Dichter, M. A., & Molinoff, P. B. (1992). Up-regulation of N-methyl-D-aspartate receptors on cultured cortical neurons after exposure to antagonists. Molecular Pharmacology, 42(1), 147-51.
Williams K, Dichter MA, Molinoff PB. Up-regulation of N-methyl-D-aspartate Receptors On Cultured Cortical Neurons After Exposure to Antagonists. Mol Pharmacol. 1992;42(1):147-51. PubMed PMID: 1353248.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Up-regulation of N-methyl-D-aspartate receptors on cultured cortical neurons after exposure to antagonists. AU - Williams,K, AU - Dichter,M A, AU - Molinoff,P B, PY - 1992/7/1/pubmed PY - 1992/7/1/medline PY - 1992/7/1/entrez SP - 147 EP - 51 JF - Molecular pharmacology JO - Mol Pharmacol VL - 42 IS - 1 N2 - 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. SN - 0026-895X UR - https://www.unboundmedicine.com/medline/citation/1353248/Up_regulation_of_N_methyl_D_aspartate_receptors_on_cultured_cortical_neurons_after_exposure_to_antagonists_ L2 - http://molpharm.aspetjournals.org/cgi/pmidlookup?view=long&pmid=1353248 DB - PRIME DP - Unbound Medicine ER -