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KMID : 0043319970200010007
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Archives of Pharmacal Research
1997 Volume.20 No. 1 p.7 ~ p.12
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Effects of L-trans-pyrrolidine-2,4-dicarboxylate, a Glutamate Uptake Inhibitor, on NMDA Receptor-mediated Calcium Influx and Extracellular Glutamate Accumulation in Cultured Cerebellar Granule Neurons
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Oh Sei-Kwan
Shin Chang-Sik
McCaslin Patrick-P.
Seong Yeon-Hee
Kim Hack-Seang
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Abstract
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Glutamate uptake inhibitor, L-trans-pyrrolidine-2, 4-dicarboxylate (PDC, ) elevated basal and N-methyl-D-aspartate (NMDA, )-induced extracellular glutamate accumulation, while it did not augment kainate -induced glutamate accumulation in cultured cerebellar granule neurons. However, pretreatment with PDC for 1 h significantly reduced NMDA-induced glutamate accumulation, but did not affect kainate-induced response. Pretreatment with glutamate for 1 h also reduced NMDA-induced glutamate accumulation, but did not kainate-induced response. Upon a brief application (3-10 min), PDC did neither induce elevation of intracellular calcium concentration nor modulate NMDA-indLiced elevation. Pretreatment with PDC for 1 h reduced NMDA-induced elevation, but it did not reduce kainate-induced elevation. These results suggest that glutamate concentration in synaptic clefts of neurana cells is increased by prolonged exposure (1 h) of the cells to PDC, and the accumulated glutamate subsequently induces selective desensitization of NMDA receptor.
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KEYWORD
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Glutamate, L-trans-pyrrolidine-2.4-dicarboxylate, NMDA (N-Methyl-D-aspartate), Calcium influx, cGMP, Cerebellar granule neurons
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