These tools will no longer be maintained as of December 31, 2024. Archived website can be found here. PubMed4Hh GitHub repository can be found here. Contact NLM Customer Service if you have questions.


Pubmed for Handhelds

PUBMED FOR HANDHELDS

Search MEDLINE/PubMed

  • Title: Glutamate-mediated neuroprotection against N-methyl-D-aspartate toxicity: a role for metabotropic glutamate receptors.
    Author: Adamchik Y, Baskys A.
    Journal: Neuroscience; 2000; 99(4):731-6. PubMed ID: 10974436.
    Abstract:
    We studied N-methyl-D-aspartate-induced cell death in organotypic hippocampal slices from seven-day-old Wistar rat pups cultured for 12-14 days in a medium containing no added glutamate. Propidium iodide fluorescence intensity was used as an indicator of cell death measured with the help of confocal microscopy. Exposure of slices for 2h to L-glutamate (1-500 microM) prior to the N-methyl-D-aspartate challenge significantly reduced N-methyl-D-aspartate-induced cell death. Glutamate at 10 and 500 microM concentrations was highly protective against N-methyl-D-aspartate-induced cell death, but was less protective at the 1 microM concentration. The protection was not blocked by the Na(+) channel blocker tetrodotoxin (1 microM), the N-methyl-D-aspartate receptor antagonist D-2-amino-5-phosphonopentanoic acid (20 microM) or the alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionate receptor antagonist 6-cyano-7-nitroquinoxaline-2,3-dione (20 microM). 1S, 3R-1-Aminocyclopentane-trans-1,3-dicarboxylic acid, an agonist at metabotropic glutamate receptor types 1, 2/3 and 5, was protective at 100 microM but not at 50 microM. In contrast, the ionotropic glutamate receptor agonist aspartate (250 microM) facilitated N-methyl-D-aspartate toxicity. Treatment of slices with the protein kinase C inhibitor staurosporine (0.2 microM) or antisense oligonucleotide (10nM, 72 h) that selectively inhibits metabotropic glutamate receptor type 5 synthesis significantly reduced glutamate protection. These results suggest that ambient glutamate may reduce nerve cell susceptibility to injury caused by excessive N-methyl-D-aspartate receptor activation by acting at metabotropic glutamate receptors linked to protein kinase C.
    [Abstract] [Full Text] [Related] [New Search]