Heterogeneity of sodium‐dependent excitatory amino uptake mechanisms in rat brain

Abstract

The pharmacologic and kinetic characteristics of sodium-dependent uptake of [3H]L-glutamate, [3H]D-aspartate, and [3H]L-aspartate into crude synaptosomal preparations of rat corpus striatum and cerebellum have been examined in vitro. In cerebellum the apparent Kts and Vmax for the three excitatory amino acids were identical whereas in striatal synaptosomes, the Vmax for [3H]L-glutamate was 30% greater (P less than or equal to .001) than for [3H]D-aspartate and 50% greater (P less than or equal to .001) than for [3H]L-aspartate. L-Amino adipic acid inhibited the uptake of the three amino acids in both regions of brain was 15- to 20-fold more potent in cerebellum than in striatum. In contrast, dihydrokainic acid inhibited transport processes in the corpus striatum but was without activity in cerebellar preparations. The neurotoxin kainic acid blocked only a portion (60%) of [3H]L-glutamate and [3H]D-aspartate uptake in cerebellum while completely inhibiting amino acid transport in corpus striatum. Three days post kainic acid lesion, [3H]D-aspartate uptake was attenuated more than [3H]L-glutamate uptake in the corpus striatum; destruction of corticostriatal afferents reduced [3H]L-glutamate to a greater extent than [3H]D-aspartate. Various lesions of the cerebellum affected excitatory amino acid transport processes to a similar extent. These results suggest that excitatory amino acid transport systems are pharmacologically distinct in different brain regions and may be heterogeneous within a single region.

The Glutamate Transporter GLT1a Is Expressed in Excitatory Axon Terminals of Mature Hippocampal Neurons

“…The identification of GLT1 as a presynaptic transporter is fully compatible with the available evidence, exhaustively reviewed by Danbolt (2001): the presence of transcripts for GLT1 in neurons throughout the forebrain (Schmitt et al, 1996;Torp et al, 1997;Berger and Hediger, 1998); the demonstration of glutamate uptake into cortical synaptosomes (Beart, 1976) that is inhibited by dihydrokainate (Ferkany and Coyle, 1986;Robinson et al, 1993;Koch et al, 1999;Suchak et al, 2003), which, at low concentrations (Ͻ300 M), is an inhibitor exclusively of GLT1 among the known transporters (Arriza et al, 1994;Tan et al, 1999;Chen et al, 2002;Kalandadze et al, 2002); the expression of GLT1 in neurons in vitro (Mennerick et al, 1998;Wang et al, 1998;Chen et al, 2002); and the increase in cross-talk between neighboring synapses by dihydrokainate (Asztely et al, 1997;Bergles and Jahr, 1998). The simplest explanation for these observations is that presynaptic uptake of glutamate is, in fact, mediated by the expression of GLT1, at least in some excitatory terminals.…”

Inhibition of glutamate uptake by a polypeptide toxin (phoneutriatoxin 3-4) from the spider Phoneutria nigriventer

“…These observations could reflect the heterogeneity and distinct pharmacological sensitivity of glutamate transporters present in synaptosomes [43,44] and cultured cells [45,46]. In fact, the experiments performed with GPVs, which is a preparation rich in GLAST and GLT-1, reinforce this view, because a much smaller effect of Tx3-4 was observed in comparison with synaptosomes ; this suggests that the toxin might have some specificity towards one or more neuronal types of glutamate transporter, such as EAAC1.…”

The glutamatergic nerve terminal

“…A number of inhibitors of the acidic amino acid transporter have been described, including cis-1 -aminocyclobutane-1,3-dicarboxylic acid (Fletcher et al, 1991), homocysteic acid (Griffiths et al, 1989) kainate and dihydrokainate (Ferkany and Coyle, 1986;Pocock et al, 1988). Some diversity of the presynaptic transporter is indicated by the failure of dihydrokainate to inhibit uptake into cerebellar synaptosomes (Ferkany and Coyle, 1986).…”

“…Some diversity of the presynaptic transporter is indicated by the failure of dihydrokainate to inhibit uptake into cerebellar synaptosomes (Ferkany and Coyle, 1986). Gangliosides have been reported to stimulate glutamate transport (Hollmann and Seifert, 1989).…”