RT Journal Article
SR Electronic
T1 Glutamate uptake disguises neurotoxic potency of glutamate agonists in cerebral cortex in dissociated cell culture
JF The Journal of Neuroscience
JO J. Neurosci.
FD Society for Neuroscience
SP 56
OP 61
DO 10.1523/JNEUROSCI.12-01-00056.1992
VO 12
IS 1
A1 Rosenberg, PA
A1 Amin, S
A1 Leitner, M
YR 1992
UL http://www.jneurosci.org/content/12/1/56.abstract
AB The pharmacological properties of glutamate agonists were compared in astrocyte-rich and astrocyte-poor cultures derived from embryonic rat cerebral cortex. The object of this investigation was to determine the extent to which glutamate uptake might influence the receptor-mediated neurotoxic actions of these compounds. In astrocyte-rich cultures, using 30 min exposures, we observed that the potencies of the poorly transported agonists NMDA (35 microM) and D-glutamate (89 microM) were higher than that of L-glutamate (205 microM). In astrocyte-poor cultures, L-glutamate was much more potent, with an EC50 of 5 +/- 4 microM (3–12 microM), for a 30 min exposure, whereas the potencies of NMDA and D-glutamate were essentially unchanged. L- and D-aspartate were also more effective in astrocyte-poor cultures, again with EC50 values of approximately 6–10 microM, as compared with 130 and 108 microM, respectively, in astrocyte-rich cultures. In other experiments, blocking sodium-dependent glutamate uptake in astrocyte-rich cultures, by using a sodium-free medium, made glutamate as potent an agonist as in astrocyte-poor cultures. Finally, we directly assessed the glutamate uptake system in astrocyte-rich and astrocyte-poor cultures and found that uptake was reduced approximately 25-fold in the astrocyte-poor cultures. These results show that in the presence of abundant astrocytes the neurotoxic potencies of L-glutamate, L-aspartate, and D- aspartate are substantially under-estimated.