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N-methyl-D-aspartate exposure blocks glutamate toxicity in cultured cerebellar granule cells.
Mol Pharmacol. 1992 Aug; 42(2):210-6.MP

Abstract

Exposure of cultured cerebellar granule cells to glutamate results in a concentration-dependent (EC50 = 22.7 +/- 0.4 microM) and delayed (24-72 hr) neurotoxicity, which is blocked by the specific N-methyl-D-aspartate (NMDA) receptor antagonists 2-amino-5-phosphovalerate and MK-801 but is unaffected by the non-NMDA receptor antagonists 6-cyano-7-nitroquinoxaline-2,3-dione and 6,7-dinitroquinoxaline-2,3-dione. Although glutamate toxicity in these cells is mediated by the NMDA subtype of glutamate receptor, pretreatment of cerebellar granule cells with subtoxic concentrations of NMDA markedly antagonizes the neurotoxic actions of glutamate, with an IC50 of 55 +/- 4 microM. The neuroprotective effect of NMDA requires a preincubation time of approximately 120 min to be fully manifested and does not require the presence of NMDA during glutamate exposure. These data demonstrate that NMDA receptors mediate both neurotoxicity and neuroprotection in cerebellar granule cells. Among four glutamate receptor agonists tested (NMDA, quisqualate, ibotenate, and kainate), only NMDA was able to provide a robust neuroprotection against glutamate toxicity. Quisqualate was neither neurotoxic nor neuroprotective, whereas ibotenate, which was nontoxic by itself, induced a small degree of neuroprotection. In contrast, kainate, which was neurotoxic to cerebellar granule cells, also provided considerable neuroprotection against glutamate toxicity. Because preincubation of cerebellar granule cells with NMDA fails to alter NMDA receptor-mediated phosphoinositide hydrolysis or the specific binding of [3H]MK-801 to NMDA receptors, it appears that the neuroprotective effects of NMDA are not due to NMDA receptor desensitization.

Authors+Show Affiliations

Section on Molecular Neurobiology, National Institute of Mental Health, Bethesda, Maryland 20892.No affiliation info availableNo affiliation info available

Pub Type(s)

Comparative Study
Journal Article

Language

eng

PubMed ID

1355259

Citation

Chuang, D M., et al. "N-methyl-D-aspartate Exposure Blocks Glutamate Toxicity in Cultured Cerebellar Granule Cells." Molecular Pharmacology, vol. 42, no. 2, 1992, pp. 210-6.
Chuang DM, Gao XM, Paul SM. N-methyl-D-aspartate exposure blocks glutamate toxicity in cultured cerebellar granule cells. Mol Pharmacol. 1992;42(2):210-6.
Chuang, D. M., Gao, X. M., & Paul, S. M. (1992). N-methyl-D-aspartate exposure blocks glutamate toxicity in cultured cerebellar granule cells. Molecular Pharmacology, 42(2), 210-6.
Chuang DM, Gao XM, Paul SM. N-methyl-D-aspartate Exposure Blocks Glutamate Toxicity in Cultured Cerebellar Granule Cells. Mol Pharmacol. 1992;42(2):210-6. PubMed PMID: 1355259.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - N-methyl-D-aspartate exposure blocks glutamate toxicity in cultured cerebellar granule cells. AU - Chuang,D M, AU - Gao,X M, AU - Paul,S M, PY - 1992/8/1/pubmed PY - 1992/8/1/medline PY - 1992/8/1/entrez SP - 210 EP - 6 JF - Molecular pharmacology JO - Mol Pharmacol VL - 42 IS - 2 N2 - Exposure of cultured cerebellar granule cells to glutamate results in a concentration-dependent (EC50 = 22.7 +/- 0.4 microM) and delayed (24-72 hr) neurotoxicity, which is blocked by the specific N-methyl-D-aspartate (NMDA) receptor antagonists 2-amino-5-phosphovalerate and MK-801 but is unaffected by the non-NMDA receptor antagonists 6-cyano-7-nitroquinoxaline-2,3-dione and 6,7-dinitroquinoxaline-2,3-dione. Although glutamate toxicity in these cells is mediated by the NMDA subtype of glutamate receptor, pretreatment of cerebellar granule cells with subtoxic concentrations of NMDA markedly antagonizes the neurotoxic actions of glutamate, with an IC50 of 55 +/- 4 microM. The neuroprotective effect of NMDA requires a preincubation time of approximately 120 min to be fully manifested and does not require the presence of NMDA during glutamate exposure. These data demonstrate that NMDA receptors mediate both neurotoxicity and neuroprotection in cerebellar granule cells. Among four glutamate receptor agonists tested (NMDA, quisqualate, ibotenate, and kainate), only NMDA was able to provide a robust neuroprotection against glutamate toxicity. Quisqualate was neither neurotoxic nor neuroprotective, whereas ibotenate, which was nontoxic by itself, induced a small degree of neuroprotection. In contrast, kainate, which was neurotoxic to cerebellar granule cells, also provided considerable neuroprotection against glutamate toxicity. Because preincubation of cerebellar granule cells with NMDA fails to alter NMDA receptor-mediated phosphoinositide hydrolysis or the specific binding of [3H]MK-801 to NMDA receptors, it appears that the neuroprotective effects of NMDA are not due to NMDA receptor desensitization. SN - 0026-895X UR - https://www.unboundmedicine.com/medline/citation/1355259/N_methyl_D_aspartate_exposure_blocks_glutamate_toxicity_in_cultured_cerebellar_granule_cells_ L2 - http://molpharm.aspetjournals.org/cgi/pmidlookup?view=long&pmid=1355259 DB - PRIME DP - Unbound Medicine ER -