PHARMACOLOGY OF SODIUM-DEPENDENT HIGH-AFFINITY L-[H-3]GLUTAMATE TRANSPORT IN GLIAL CULTURES

Citation
Ab. Garlin et al., PHARMACOLOGY OF SODIUM-DEPENDENT HIGH-AFFINITY L-[H-3]GLUTAMATE TRANSPORT IN GLIAL CULTURES, Journal of neurochemistry, 64(6), 1995, pp. 2572-2580
Citations number
39
Categorie Soggetti
Biology,Neurosciences
Journal title
ISSN journal
00223042
Volume
64
Issue
6
Year of publication
1995
Pages
2572 - 2580
Database
ISI
SICI code
0022-3042(1995)64:6<2572:POSHLT>2.0.ZU;2-E
Abstract
Pharmacological and molecular biological studies provide evidence for subtypes of sodium-dependent high-affinity glutamate (Glu) transport i n 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-[H-3]Glu transport we re characterized using astrocyte-enriched cultures prepared from cereb ellum and cortex. In both brain regions, the kinetic data for sodium-d ependent transport were consistent with a single site with K-m values of 91 +/- 17 mu M in cortical glial cells and 66 +/- 23 mu M in cerebe llar glial cells. The capacities were 6.1 +/- 1.6 nmol/mg of protein/m in in cortical glial cells and 8.4 +/- 0.9 nmol/mg of protein/min in c erebellar glial cells. The potencies of similar to 40 excitatory amino acid analogues for inhibition of sodium-dependent transport into glia l cells prepared from cortex and cerebellum were examined, including c ompounds that are selective inhibitors of transport in synaptosomes pr epared from either cerebellum or cortex. Of the analogues tested, 14 i nhibited transport activity by > 50% at 1 mM concentrations. Unlike L- [H-3]Glu transport in synaptosomes prepared from cerebellum or cortex, there were no large differences between the potencies of compounds fo r inhibition of transport measured in glial cells prepared from these two brain regions. With the exception of (2S,1'R,2'R)-2-(carboxy-cyclo propyl)glycine and L-alpha-aminoadipate, all of the compounds examined were similar to 10-200-fold less potent as inhibitors of L-[H-3]Glu t ransport measured in glial cells than as inhibitors of transport measu red in synaptosomes prepared from their respective brain regions. The pharmacology of transport measured in these glial cells differs from t he reported pharmacology of the cloned Glu transporters, suggesting th e existence of additional uncloned Glu transporters or Glu transporter subunits.