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Agonist‐induced Down‐regulation of NMDA Receptors in Cerebellar Granule Cells in Culture
Author(s) -
Resink A.,
Villa M.,
Boer G. J.,
Möhler H.,
Balázs R.
Publication year - 1995
Publication title -
european journal of neuroscience
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.346
H-Index - 206
eISSN - 1460-9568
pISSN - 0953-816X
DOI - 10.1111/j.1460-9568.1995.tb00691.x
Subject(s) - nmda receptor , agonist , receptor , chemistry , in vitro , protein subunit , pharmacology , biology , microbiology and biotechnology , biochemistry , gene
In contrast to the acute toxic effect of NMDA on mature cerebellar granule cells, chronic treatment with NMDA (140 μM from 1 to 9 days in vitro ) did not compromise cell survival. Such treatment markedly suppressed NMDA receptor activity: at 8 days in vitro NMDA‐induced 45 Ca 2+ influx was reduced by ‐60% and acute exposure to NMDA (highest concentration tested, 1 mM) at 9 days in vitro did not cause detectable toxicity. The reduction in NMDA receptor activity was accompanied by a significant decrease (±80% at 9 days in vitro ) in the level of the NR1 and the NR2A NMDA receptor subunit protein, detected using the selective photoaffinity ligand [ 125 I]CGP55802A. It seems, therefore, that the agonist‐induced decrease in NMDA receptor activity is due to receptor down‐regulation. In contrast to the marked influence of chronic NMDA exposure on the cellular content of the NMDA receptor subunit proteins, mRNA levels of the different subunits (NR1, NR2A, NR2B and NR2C) were not significantly affected. It seems, therefore, that agonist‐induced down‐regulation of the NMDA receptor involves critically mRNA translation and/or post‐translational regulation.