Inhibition of nitric oxide formation does not protect murine cortical cell cultures from N-methyl-d-aspartate neurotoxicity

Sandra J. Hewett; John A. Corbett; Michael L. McDaniel; Dennis W. Choi

doi:10.1016/0006-8993(93)91078-7

Inhibition of nitric oxide formation does not protect murine cortical cell cultures from N-methyl-d-aspartate neurotoxicity

Sandra J. Hewett, John A. Corbett, Michael L. McDaniel, Dennis W. Choi

Research output: Contribution to journal › Article › peer-review

71 Scopus citations

Abstract

We examined the role of nitric oxide in N-methyl-d-aspartate (NMDA) receptor-mediated neurotoxicity in rat and mouse primary cortical cell cultures. In rat and mouse cultures, the NO synthase inhibitor, N^G-Nitro-l-arginine, blocked cGMP formation but not neuronal cell death following a 5-10 min exposure to 300-500 μM NMDA. N^G-Monomethyl-l-arginine was also unable to prevent neuronal death. In contrast, the non-competitive NMDA receptor antagonist, dextrophan, prevented both cGMP formation and cell death. While other data suggest that the synthesis of nitric oxide can mediate NMDA receptor-mediated neurotoxicity, present results suggest that such synthesis is not necessarily required.

Original language	English (US)
Pages (from-to)	337-341
Number of pages	5
Journal	Brain Research
Volume	625
Issue number	2
DOIs	https://doi.org/10.1016/0006-8993(93)91078-7
State	Published - Oct 22 1993
Externally published	Yes

Keywords

Cell culture
Cortex
N-Nitro-l-arginine
NMDA
Neuronal damage
Nitric oxide
cGMP

ASJC Scopus subject areas

General Neuroscience
Molecular Biology
Clinical Neurology
Developmental Biology

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10.1016/0006-8993(93)91078-7

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title = "Inhibition of nitric oxide formation does not protect murine cortical cell cultures from N-methyl-d-aspartate neurotoxicity",

abstract = "We examined the role of nitric oxide in N-methyl-d-aspartate (NMDA) receptor-mediated neurotoxicity in rat and mouse primary cortical cell cultures. In rat and mouse cultures, the NO synthase inhibitor, NG-Nitro-l-arginine, blocked cGMP formation but not neuronal cell death following a 5-10 min exposure to 300-500 μM NMDA. NG-Monomethyl-l-arginine was also unable to prevent neuronal death. In contrast, the non-competitive NMDA receptor antagonist, dextrophan, prevented both cGMP formation and cell death. While other data suggest that the synthesis of nitric oxide can mediate NMDA receptor-mediated neurotoxicity, present results suggest that such synthesis is not necessarily required.",

keywords = "Cell culture, Cortex, N-Nitro-l-arginine, NMDA, Neuronal damage, Nitric oxide, cGMP",

author = "Hewett, {Sandra J.} and Corbett, {John A.} and McDaniel, {Michael L.} and Choi, {Dennis W.}",

note = "Funding Information: The authors thank Kamala Rose, Cynthia Tjan, and Connie Marshall for excellent technical assistance. This work was supported by NIH Grants NS30337 (D.W.C.) and DK06181 (M.L.M.) as well as a grant from the Alzheimer's Disease and Related Disorders Association (D.W.C.) and a Washington University/Monsanto Biomedical Program grant (M.L.M.). S.J.H was partially supported from NIH Training Grant 2 T32 NS07027-17. J.A.C. was supported by NRSA F32DR08748.",

year = "1993",

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doi = "10.1016/0006-8993(93)91078-7",

language = "English (US)",

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pages = "337--341",

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T1 - Inhibition of nitric oxide formation does not protect murine cortical cell cultures from N-methyl-d-aspartate neurotoxicity

AU - Hewett, Sandra J.

AU - Corbett, John A.

AU - McDaniel, Michael L.

AU - Choi, Dennis W.

N1 - Funding Information: The authors thank Kamala Rose, Cynthia Tjan, and Connie Marshall for excellent technical assistance. This work was supported by NIH Grants NS30337 (D.W.C.) and DK06181 (M.L.M.) as well as a grant from the Alzheimer's Disease and Related Disorders Association (D.W.C.) and a Washington University/Monsanto Biomedical Program grant (M.L.M.). S.J.H was partially supported from NIH Training Grant 2 T32 NS07027-17. J.A.C. was supported by NRSA F32DR08748.

PY - 1993/10/22

Y1 - 1993/10/22

N2 - We examined the role of nitric oxide in N-methyl-d-aspartate (NMDA) receptor-mediated neurotoxicity in rat and mouse primary cortical cell cultures. In rat and mouse cultures, the NO synthase inhibitor, NG-Nitro-l-arginine, blocked cGMP formation but not neuronal cell death following a 5-10 min exposure to 300-500 μM NMDA. NG-Monomethyl-l-arginine was also unable to prevent neuronal death. In contrast, the non-competitive NMDA receptor antagonist, dextrophan, prevented both cGMP formation and cell death. While other data suggest that the synthesis of nitric oxide can mediate NMDA receptor-mediated neurotoxicity, present results suggest that such synthesis is not necessarily required.

AB - We examined the role of nitric oxide in N-methyl-d-aspartate (NMDA) receptor-mediated neurotoxicity in rat and mouse primary cortical cell cultures. In rat and mouse cultures, the NO synthase inhibitor, NG-Nitro-l-arginine, blocked cGMP formation but not neuronal cell death following a 5-10 min exposure to 300-500 μM NMDA. NG-Monomethyl-l-arginine was also unable to prevent neuronal death. In contrast, the non-competitive NMDA receptor antagonist, dextrophan, prevented both cGMP formation and cell death. While other data suggest that the synthesis of nitric oxide can mediate NMDA receptor-mediated neurotoxicity, present results suggest that such synthesis is not necessarily required.

KW - Cell culture

KW - Cortex

KW - N-Nitro-l-arginine

KW - NMDA

KW - Neuronal damage

KW - Nitric oxide

KW - cGMP

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Inhibition of nitric oxide formation does not protect murine cortical cell cultures from N-methyl-d-aspartate neurotoxicity

Abstract

Keywords

ASJC Scopus subject areas

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