Abstract
Previously, we showed that dopamine protects cultured retinal neurons from N-methyl-D-aspartate (NMDA) receptor mediated-glutamate excitotoxicity via dopamine D1 receptor. This study has demonstrated for the first time that nitric oxide synthase (NOS) plays a crucial role in dopamine-induced neuroprotection. Our patch clamp study has shown that dopamine does not affect the NMDA-induced whole cell current. Dopamine or SKF38393 (D1 receptor agonist) inhibited ionomycin (calcium ionophore)-induced toxicity, while dopamine did not affect S-nitrosocysteine (NO donor)-induced toxicity. Biochemical analysis on enzymatic activities has shown that dopamine or cAMP (which is generated through D1 receptor stimulation) inhibits glutamate induced-NOS activation. These results suggest that dopamine inhibits glutamate induced-NOS activation via D1 receptor, resulting in the protection of retinal neurons.
MeSH terms
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2,3,4,5-Tetrahydro-7,8-dihydroxy-1-phenyl-1H-3-benzazepine / pharmacology
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Animals
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Cells, Cultured
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Dopamine / metabolism
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Dopamine / pharmacology*
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Dopamine Agonists / pharmacology
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Enzyme Activation
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Excitatory Amino Acid Agonists / pharmacology*
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Kainic Acid / pharmacology
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N-Methylaspartate / pharmacology
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Neurons / enzymology*
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Nitric Oxide Synthase / metabolism*
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Nitric Oxide Synthase Type I
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Patch-Clamp Techniques
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Rats
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Rats, Wistar
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Receptors, Dopamine D1 / physiology
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Receptors, N-Methyl-D-Aspartate / agonists
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Receptors, N-Methyl-D-Aspartate / physiology*
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Retina / cytology
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Retina / drug effects
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Retina / enzymology*
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alpha-Amino-3-hydroxy-5-methyl-4-isoxazolepropionic Acid / pharmacology
Substances
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Dopamine Agonists
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Excitatory Amino Acid Agonists
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Receptors, Dopamine D1
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Receptors, N-Methyl-D-Aspartate
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N-Methylaspartate
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2,3,4,5-Tetrahydro-7,8-dihydroxy-1-phenyl-1H-3-benzazepine
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alpha-Amino-3-hydroxy-5-methyl-4-isoxazolepropionic Acid
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Nitric Oxide Synthase
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Nitric Oxide Synthase Type I
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Nos1 protein, rat
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Kainic Acid
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Dopamine