Nitric oxide inhibitors attenuate N-methyl-d-aspartate excitotoxicity in rat hippocampal slices

Yukitoshi Izumi; Ann M. Benz; David B. Clifford; Charles F. Zorumski

doi:10.1016/0304-3940(92)90442-A

Nitric oxide inhibitors attenuate N-methyl-d-aspartate excitotoxicity in rat hippocampal slices

Yukitoshi Izumi, Ann M. Benz, David B. Clifford, Charles F. Zorumski

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Abstract

To investigate whether nitric oxide (NO) plays a role in the neurotoxicity produced by N-methyl-d-aspartate (NMDA) we have examined the effects of NO inhibitors on NMDA-mediated neurodegeneration in the CA1 region of rat hippocampal slices. l-N^G-Monomethylarginine, l-N^G-nitroarginine and hemoglobin markedly diminished the toxicity produced by activation of NMDA receptors without interfering with NMDA receptor-mediated ion currents or synaptic responses. The neuroprotective effects are reversed by coapplication of l-arginine with the NO synthase inhibitors. These results suggest that activation of the NO system is an important component of the biochemical cascade leading to neurodegeneration produced by NMDA receptors.

Original language	English
Pages (from-to)	227-230
Number of pages	4
Journal	Neuroscience Letters
Volume	135
Issue number	2
DOIs	https://doi.org/10.1016/0304-3940(92)90442-A
State	Published - Feb 3 1992

Keywords

Calcium
Excitotoxicity
Hemoglobin
Hippocampus
N-Methyl-d-aspartate
Nitric oxide

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10.1016/0304-3940(92)90442-A

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title = "Nitric oxide inhibitors attenuate N-methyl-d-aspartate excitotoxicity in rat hippocampal slices",

abstract = "To investigate whether nitric oxide (NO) plays a role in the neurotoxicity produced by N-methyl-d-aspartate (NMDA) we have examined the effects of NO inhibitors on NMDA-mediated neurodegeneration in the CA1 region of rat hippocampal slices. l-NG-Monomethylarginine, l-NG-nitroarginine and hemoglobin markedly diminished the toxicity produced by activation of NMDA receptors without interfering with NMDA receptor-mediated ion currents or synaptic responses. The neuroprotective effects are reversed by coapplication of l-arginine with the NO synthase inhibitors. These results suggest that activation of the NO system is an important component of the biochemical cascade leading to neurodegeneration produced by NMDA receptors.",

keywords = "Calcium, Excitotoxicity, Hemoglobin, Hippocampus, N-Methyl-d-aspartate, Nitric oxide",

author = "Yukitoshi Izumi and Benz, {Ann M.} and Clifford, {David B.} and Zorumski, {Charles F.}",

note = "Funding Information: This work was supported by fellowships from the Mc-Donnell Center for Higher Brain Function and the Bantly Foundation, Physician Scientist Award MH00630 and Grants AG05681 and MH45493. The authors thank Drs. John W. Olney and Madelon T. Price for helpful advice and suggestions and Jianxin Que for technical assistance.",

year = "1992",

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doi = "10.1016/0304-3940(92)90442-A",

language = "English",

volume = "135",

pages = "227--230",

journal = "Neuroscience Letters",

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T1 - Nitric oxide inhibitors attenuate N-methyl-d-aspartate excitotoxicity in rat hippocampal slices

AU - Izumi, Yukitoshi

AU - Benz, Ann M.

AU - Clifford, David B.

AU - Zorumski, Charles F.

N1 - Funding Information: This work was supported by fellowships from the Mc-Donnell Center for Higher Brain Function and the Bantly Foundation, Physician Scientist Award MH00630 and Grants AG05681 and MH45493. The authors thank Drs. John W. Olney and Madelon T. Price for helpful advice and suggestions and Jianxin Que for technical assistance.

PY - 1992/2/3

Y1 - 1992/2/3

N2 - To investigate whether nitric oxide (NO) plays a role in the neurotoxicity produced by N-methyl-d-aspartate (NMDA) we have examined the effects of NO inhibitors on NMDA-mediated neurodegeneration in the CA1 region of rat hippocampal slices. l-NG-Monomethylarginine, l-NG-nitroarginine and hemoglobin markedly diminished the toxicity produced by activation of NMDA receptors without interfering with NMDA receptor-mediated ion currents or synaptic responses. The neuroprotective effects are reversed by coapplication of l-arginine with the NO synthase inhibitors. These results suggest that activation of the NO system is an important component of the biochemical cascade leading to neurodegeneration produced by NMDA receptors.

AB - To investigate whether nitric oxide (NO) plays a role in the neurotoxicity produced by N-methyl-d-aspartate (NMDA) we have examined the effects of NO inhibitors on NMDA-mediated neurodegeneration in the CA1 region of rat hippocampal slices. l-NG-Monomethylarginine, l-NG-nitroarginine and hemoglobin markedly diminished the toxicity produced by activation of NMDA receptors without interfering with NMDA receptor-mediated ion currents or synaptic responses. The neuroprotective effects are reversed by coapplication of l-arginine with the NO synthase inhibitors. These results suggest that activation of the NO system is an important component of the biochemical cascade leading to neurodegeneration produced by NMDA receptors.

KW - Calcium

KW - Excitotoxicity

KW - Hemoglobin

KW - Hippocampus

KW - N-Methyl-d-aspartate

KW - Nitric oxide

UR - http://www.scopus.com/inward/record.url?scp=0026501674&partnerID=8YFLogxK

U2 - 10.1016/0304-3940(92)90442-A

DO - 10.1016/0304-3940(92)90442-A

M3 - Article

C2 - 1625799

AN - SCOPUS:0026501674

SN - 0304-3940

VL - 135

SP - 227

EP - 230

JO - Neuroscience Letters

JF - Neuroscience Letters

IS - 2

ER -

Nitric oxide inhibitors attenuate N-methyl-d-aspartate excitotoxicity in rat hippocampal slices

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Keywords

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