Two pathways of nitric oxide production through glutamate receptors in the rat cerebellum in vivo

Kiyofumi Yamada, Toshitaka Nabeshima

Research output: Contribution to journalArticle

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Abstract

The effects of N-methyl-D-aspartate (NMDA), (+)-α-amino-3-hydroxy-5-methylisoxazole-4-propionic acid (AMPA), and trans-(±)-1-amino-(1S,3R)-cyclopentanedicarboxylic acid (ACPD) on nitric oxide (NO) production in the cerebellum of conscious rats were investigated by measuring the levels of total NO metabolites (nitrite plus nitrate, NO(x)-) in dialysates obtained by in vivo microdialysis. All glutamate receptor agonists dose-dependently increased NO(x)- levels. Pharmacological characterization with various glutamate receptor antagonists indicated that the effects of NMDA, AMPA and ACPD are mediated by NMDA, non-NMDA, and L(+)-2-amino-3-phosphonopropionic acid (L(+)-AP-3)-sensitive metabotropic glutamate receptors, respectively. The NO synthase (NOS) inhibitors, including N(G)-nitro-L-arginine methyl ester (L-NAME), N(G)-nitro-L-arginine (L-NA), 7-nitroindazole (7-NI), and NO-monomethyl-L-arginine, inhibited NMDA-induced, but not AMPA- or ACPD-induced, increase in NO(x)- levels. L-Arginine enhanced NMDA-induced, but not AMPA- or ACPD-induced, increase in NO(x)- levels. Cytochrome P-450 inhibitors, SKF525A and erythromycin, inhibited the effect of NMDA, but not AMPA or ACPD. These results suggest that AMPA and ACPD may induce NO production through a NOS-independent pathway although NMDA receptor-mediated NO production is dependent on NOS activity in the rat cerebellum in vivo.

Original languageEnglish
Pages (from-to)93-102
Number of pages10
JournalNeuroscience Research
Volume28
Issue number2
DOIs
Publication statusPublished - 01-06-1997

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Glutamate Receptors
Cerebellum
Nitric Oxide
N-Methylaspartate
Nitric Oxide Synthase
Arginine
NG-Nitroarginine Methyl Ester
Excitatory Amino Acid Agonists
D-Aspartic Acid
Excitatory Amino Acid Antagonists
Dialysis Solutions
Microdialysis
Erythromycin
Nitrites
N-Methyl-D-Aspartate Receptors
Nitrates
propionic acid
bucide
Pharmacology
Acids

All Science Journal Classification (ASJC) codes

  • Neuroscience(all)

Cite this

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Two pathways of nitric oxide production through glutamate receptors in the rat cerebellum in vivo. / Yamada, Kiyofumi; Nabeshima, Toshitaka.

In: Neuroscience Research, Vol. 28, No. 2, 01.06.1997, p. 93-102.

Research output: Contribution to journalArticle

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