Pharmacology of Sodium-Dependent High-Affinity l-[3H]Glutamate Transport in Glial Cultures
Version of Record online: 23 NOV 2002
Journal of Neurochemistry
Volume 64, Issue 6, pages 2572–2580, June 1995
How to Cite
Garlin, A. B., Sinor, A. D., Sinor, J. D., Jee, S. H., Grinspan, J. B. and Robinson, M. B. (1995), Pharmacology of Sodium-Dependent High-Affinity l-[3H]Glutamate Transport in Glial Cultures. Journal of Neurochemistry, 64: 2572–2580. doi: 10.1046/j.1471-4159.1995.64062572.x
- Issue online: 23 NOV 2002
- Version of Record online: 23 NOV 2002
- Resubmitted manuscript received October 12, 1994; revised manuscript received December 6, 1994; accepted December 7, 1994.
- Excitatory amino acids;
Abstract: Pharmacological and molecular biological studies provide evidence for subtypes of sodium-dependent high-affinity glutamate (Glu) transport in the mammalian CNS. At least some of these transporters appear to be selectively expressed in different brain regions or by different cell types. In the present study, the properties of l-[3H]Glu transport were characterized using astrocyte-enriched cultures prepared from cerebellum and cortex. In both brain regions, the kinetic data for sodium-dependent transport were consistent with a single site with Km values of 91 ± 17 µM in cortical glial cells and 66 ± 23 µM in cerebellar glial cells. The capacities were 6.1 ± 1.6 nmol/mg of protein/min in cortical glial cells and 8.4 ± 0.9 nmol/mg of protein/min in cerebellar glial cells. The potencies of ∼40 excitatory amino acid analogues for inhibition of sodium-dependent transport into glial cells prepared from cortex and cerebellum were examined, including compounds that are selective inhibitors of transport in synaptosomes prepared from either cerebellum or cortex. Of the analogues tested, 14 inhibited transport activity by >50% at 1 mM concentrations. Unlike l-[3H]Glu transport in synaptosomes prepared from cerebellum or cortex, there were no large differences between the potencies of compounds for inhibition of transport measured in glial cells prepared from these two brain regions. With the exception of (2S,1′R,2′R)-2-(carboxycyclopropyl)glycine and l-α-aminoadipate, all of the compounds examined were ∼10–200-fold less potent as inhibitors of l-[3H]Glu transport measured in glial cells than as inhibitors of transport measured in synaptosomes prepared from their respective brain regions. The pharmacology of transport measured in these glial cells differs from the reported pharmacology of the cloned Glu transporters, suggesting the existence of additional uncloned Glu transporters or Glu transporter subunits.