A. Resink et al., AGONIST-INDUCED DOWN-REGULATION OF NMDA RECEPTORS IN CEREBELLAR GRANULE CELLS IN CULTURE, European journal of neuroscience, 7(8), 1995, pp. 1700-1706
In contrast to the acute toxic effect of NMDA on mature cerebellar gra
nule cells, chronic treatment with NMDA (140 mu M from 1 to 9 days in
vitro) did not compromise cell survival. Such treatment markedly suppr
essed NMDA receptor activity: at 8 days in vitro NMDA-induced Ca-45(2) influx was reduced by similar to 60% and acute exposure to NMDA (hig
hest concentration tested, 1 mM) at 9 days in vitro did not cause dete
ctable toxicity. The reduction in NMDA receptor activity was accompani
ed by a significant decrease (similar to 80% at 9 days in vitro) in th
e level of the NR1 and the NR2A NMDA receptor subunit protein, detecte
d using the selective photoaffinity ligand [I-125]CGP55802A. It seems,
therefore, that the agonist-induced decrease in NMDA receptor activit
y is due to receptor down-regulation. In contrast to the marked influe
nce of chronic NMDA exposure on the cellular content of the NMDA recep
tor 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 cr
itically mRNA translation and/or post-translational regulation.