Inhibition of glutamate-induced nitric oxide synthase activation by dopamine in cultured rat retinal neurons.
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.
Yamauchi
Tomofusa
T
Department of Ophthalmology and Visual Sciences, Graduate School of Medicine, Kyoto University, Kyoto 606-8507, Japan.
Kashii
Satoshi
S
Yasuyoshi
Hiroki
H
Zhang
Shen
S
Honda
Yoshihito
Y
Ujihara
Hisamitsu
H
Akaike
Akinori
A
D015647:2,3,4,5-Tetrahydro-7,8-dihydroxy-1-phenyl-1H-3-benzazepine / Q000494:pharmacology; D000818:Animals; D002478:Cells, Cultured; D004298:Dopamine / Q000378:metabolism / Q000494:pharmacology*; D018491:Dopamine Agonists / Q000494:pharmacology; D004789:Enzyme Activation; D018690:Excitatory Amino Acid Agonists / Q000494:pharmacology*; D007608:Kainic Acid / Q000494:pharmacology; D016202:N-Methylaspartate / Q000494:pharmacology; D009474:Neurons / Q000201:enzymology*; D019001:Nitric Oxide Synthase / Q000378:metabolism*; D052248:Nitric Oxide Synthase Type I; D018408:Patch-Clamp Techniques; D051381:Rats; D017208:Rats, Wistar; D017447:Receptors, Dopamine D1 / Q000502:physiology; D016194:Receptors, N-Methyl-D-Aspartate / Q000819:agonists / Q000502:physiology*; D012160:Retina / Q000166:cytology / Q000187:drug effects / Q000201:enzymology*; D018350:alpha-Amino-3-hydroxy-5-methyl-4-isoxazolepropionic Acid / Q000494:pharmacology
D018491:Dopamine Agonists; D018690:Excitatory Amino Acid Agonists; D017447:Receptors, Dopamine D1; D016194:Receptors, N-Methyl-D-Aspartate; D016202:N-Methylaspartate; D015647:2,3,4,5-Tetrahydro-7,8-dihydroxy-1-phenyl-1H-3-benzazepine; D018350:alpha-Amino-3-hydroxy-5-methyl-4-isoxazolepropionic Acid; D019001:Nitric Oxide Synthase; D052248:Nitric Oxide Synthase Type I; C496322:Nos1 protein, rat; D007608:Kainic Acid; D004298:Dopamine