Abstract
Activation of NMDA receptors in dissociated cerebellar granule cells reduced mitochondrial membrane potential (MMP), as measured by rhodamine 123 fluorescence in a flow cytometer. This effect was inhibited by several NMDA-receptor antagonists with the following rank order of potency: MK-801 > PCP > TCP > dextrorphan > dichlorokynurenic acid > D-AP5 > dextromethorphan. Neither spermine nor arcaine modified the NMDA-induced reduction in MMP, whereas ifenprodil and eliprodil inhibited this response in the micromolar range. The mechanism responsible for the alteration of MMP mediated by NMDA was studied. Mepacrine and dibucaine prevented the MMP reduction induced by NMDA, as did W13 (calmodulin antagonist). In contrast, this effect was not blocked by cyclooxygenase or lipooxygenase inhibitors, H7 (a protein kinase C inhibitor) or nitroarginine (nitric oxide synthase inhibitor). These data suggest a direct interaction between NMDA-receptor activation and arachidonic acid formation, and indicate that NMDA receptor-mediated effect on MMP could involve arachidonic acid.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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2-Amino-5-phosphonovalerate / pharmacology
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Anesthetics, Local / pharmacology
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Animals
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Arachidonic Acid / physiology*
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Biomarkers
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Cells, Cultured
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Cerebellum / cytology
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Dibucaine / pharmacology
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Enzyme Inhibitors / pharmacology
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Excitatory Amino Acid Agonists / pharmacology
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Excitatory Amino Acid Antagonists / pharmacology
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Flow Cytometry
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Fluorescent Dyes
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Glycine / pharmacology
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Intracellular Membranes / chemistry
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Intracellular Membranes / physiology
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Kynurenic Acid / analogs & derivatives
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Kynurenic Acid / pharmacology
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Membrane Potentials / drug effects
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Membrane Potentials / physiology
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Mitochondria / chemistry*
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Mitochondria / physiology*
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N-Methylaspartate / pharmacology
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Piperidines / pharmacology
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Quinacrine / pharmacology
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Rats
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Rats, Sprague-Dawley
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Receptors, N-Methyl-D-Aspartate / agonists
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Receptors, N-Methyl-D-Aspartate / antagonists & inhibitors
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Receptors, N-Methyl-D-Aspartate / physiology*
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Rhodamine 123
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Rhodamines
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Sulfonamides / pharmacology
Substances
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Anesthetics, Local
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Biomarkers
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Enzyme Inhibitors
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Excitatory Amino Acid Agonists
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Excitatory Amino Acid Antagonists
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Fluorescent Dyes
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Piperidines
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Receptors, N-Methyl-D-Aspartate
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Rhodamines
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Sulfonamides
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Rhodamine 123
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Arachidonic Acid
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N-Methylaspartate
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2-Amino-5-phosphonovalerate
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N-(4-aminobutyl)-5-chloro-2-naphthalenesulfonamide
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Kynurenic Acid
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Quinacrine
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Dibucaine
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ifenprodil
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5,7-dichlorokynurenic acid
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Glycine
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eliprodil