SIB-1893 reversed 6-OHDA-induced inhibitory effect on glutamate uptake of astrocytes

Abstract

Abstract: AIM: To study the effect of (E)-2-methyl-6-(2-phenylethenyl) pyridine, the metabotropic glutamate receptor5 (mGluR5) antagonist, and 6-hydroxydopamine (6-OHDA) on astrocytic glutamate uptake activity.METHODS: Rat cortical astrocytes from 1 to 2 days old rats were separated for primary culture.Glutamate uptake activity of astrocytes was determined, using isotopic techniques, by intracellular 3H-labeled D, L-glutamate concentration. In addition, the extracellular glutamate concentration was assayed by high-performance liquid chromatography(HPLC).Cell viability was assessed with the Lactate dehydrogenase (LDH) activity released into the incubation medium.RESULTS: 6-OHDA decreased astrocytic glutamate uptake in a concentration-dependent manner, but it had no effect on inducing glutamate release from astrocytes. Cell viability was also decreased in a concentration-dependent manner while LDH activity increased. SIB-1893 had no effect on normal astrocytic glutamate uptake, but increased glutamate uptake of impaired astrocytes caused by 6-OHDA.CONCLUSION: The neurotoxic mechanism of 6-OHDA may be associated with the decrease of astrocytic glutamate uptake activity. SIB-1893 can reverse the inhibitory effect induced by 6-OHDA on astrocytic glutamate uptake and therefore have neuroprotective effects.

Key words: (E)-2-methyl-6-(2-phenylethenyl) pyridine, 6-hydroxydopamine, astrocytes, glutamate, uptake, cell viability

CLC Number:

R965

ZHANG Yun, DING Jian-Hua, HU Gang. SIB-1893 reversed 6-OHDA-induced inhibitory effect on glutamate uptake of astrocytes[J]. Chinese Journal of Clinical Pharmacology and Therapeutics, 2004, 9(1): 25-28.

References

1 Mandel S, Grunblatt E, Riederer P, et al. Neuroprotective strategies in Parkinson' s disease:an update on progress[J]. CNS Drugs, 2003;17:729-62
2 Danbolt, NC.Glutamate uptake[J]. Prog Neurobiol, 2001;65:1-105
3 Gegelashvili G, Dehnes Y, Danbolt NC, et al. The high-affinity glutamate transporters GLT1, GLAST and EAAT4 are regulated via different signalling mechanisms[J]. Neurochem Int,2000;37:163-70
4 DiMonte DA, Tokar I, Langston JW.Impaired glutamate clearance as a consequence of energy failure caused by MPP(+) in astrocytic cultures[J]. Toxicol Appl Pharmacol, 1999;158:296-302
5 McCarthy KD, De Vellis J.Preparation of separate astroglial and oligodendroglial cell cultures from rat cerebral tissue[J]. J Cell Biol, 1980;85:890-902
6 Longuemare MC, Rose CR, Farrell K, et al. K+-induced reversal of astrocyte glutamate uptake is limited by compensatory changes in intracellular Na⁺[J]. Neurosci, 1999;93:285-92
7 Rao SD, Yin HZ, Weiss JH.Disruption of glial glutamate transport by reactive oxygen species produced in motor neurons[J]. J Neurosci, 2003;23:2627-33
8 Plaitakis A, Shashidharan P.Glutamate transport and metabolism in dopaminergic neurons of substantia nigra:implications for the pathogenesis of Parkinson' disease [J]. J Neurol, 2000,247l20):25-35
9 Berman SB, Hastings TG.Inhibition of glutamate transport in synaptosomes by dopamine oxidation and reactive oxygen species[J]. J Neurochem, 1997;69:1185-95
10 Deumens R, Blokland A, Prickaerts J.Modeling Parkinson' s disease in rats:an evaluation of 6-OHDA lesions of the nigrostriatal pathway[J]. Exp Neurol, 2002;175:303-17
11 Duyckaerts C, Verny M, Hauw JJ.Recent neuropathology of parkinsonian syndromes[J]. Rev Neurol (Paris), 2003;159(5Pt 2):11-8
12 Teismann P, Tieu K, et alCohen O..Pathogenic role of glial cells in Parkinson' s disease[J]. Mov Disord, 2003;18:121-9
13 Galindo MF, Jordan J, Gonzalez-Garcia C, Cena V.Chromaffin cell death induced by 6-hydroxydopamine is independent of mitochondrial swelling and caspase activation[J]. J Neurochem, 2003;84:1066-73
14 Nicoletti F, Bruno V, et alCatania MV..Group-I metabotropic glutamate receptors:hypotheses to explain their dual role in neurotoxicity and neuroprotection[J]. Neuropharmacology,1999;38:1477-84
15 Battaglia G, Fornai F, et alBusceti CL..Selective blockade of mGlu5 metabotropic glutamate receptors is protective against methamphetamine neurotoxicity[J]. J Neurosci, 2002;22:2135-41

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