Abstract
Intrastriatal administration of ammonium ions ("ammonia") via a microdialysis probe overactivates N-methyl-D-aspartate (NMDA) receptors, which results in cGMP accumulation in the microdialysates. Co-administration of a potent glycine site-specific NMDA receptor antagonist CGP 78608 ([(1S)-1-[[(7-bromo-1,2,3,4-tetrahydro-2,3-dioxo-5-quinoxalinyl)methyl]amino]ethyl]phosphonate) significantly reduced (at 20 nM) or abolished (at 100 nM) ammonia-dependent cGMP synthesis. Since NMDA receptor activation is an important causative factor in ammonia neurotoxicity, the present results suggest the glycine site of the receptor to be a potential valuable target for protective intervention.
Publication types
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Comparative Study
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Research Support, Non-U.S. Gov't
MeSH terms
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Allosteric Regulation
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Ammonia / toxicity*
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Animals
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Binding Sites
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Corpus Striatum / cytology
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Corpus Striatum / drug effects*
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Corpus Striatum / metabolism
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Cyclic GMP / metabolism*
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Glycine / metabolism*
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Male
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Microdialysis
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Microinjections
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Neurons / drug effects*
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Neurons / metabolism
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Neurotoxins / toxicity
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Nitric Oxide / metabolism
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Organophosphonates / pharmacology*
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Quinoxalines / pharmacology*
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Rats
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Rats, Sprague-Dawley
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Receptors, N-Methyl-D-Aspartate / antagonists & inhibitors*
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Receptors, N-Methyl-D-Aspartate / classification
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Receptors, N-Methyl-D-Aspartate / metabolism
Substances
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((1S)-1-(((7-bromo-1,2,3,4-tetrahydro-2,3-dioxo-5-quinoxalinyl)methyl)amino)ethyl)phosphonate
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Neurotoxins
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Organophosphonates
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Quinoxalines
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Receptors, N-Methyl-D-Aspartate
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Nitric Oxide
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Ammonia
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Cyclic GMP
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Glycine