Nitric oxide synthase: Irreversible inhibition by L-NG-Nitroarginine in brain in vitro and in vivo

Mary A. Dwyer; David S. Bredt; Solomon H. Snyder

doi:10.1016/0006-291X(91)90403-T

Nitric oxide synthase: Irreversible inhibition by L-N^G-Nitroarginine in brain in vitro and in vivo

Mary A. Dwyer, David S. Bredt, Solomon H. Snyder

School of Medicine

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

351 Scopus citations

Abstract

Inhibition of nitric oxide (NO) synthase activity by L-N^G-Nitroarginine (NO₂Arg) in brain preparations is not reversed by dialysis and is enhanced by prolonged preincubation of NO₂Arg with the enzyme. By contrast, the weaker inhibition by NO₂Arg of macrophage NO synthase is fully reversible. NO₂Arg inhibits NO synthase activity in the brain after i.p. administration of 5 or 50 mg/kg. This in vivo inhibition also appears to be irreversible. The potent in vivo inhibition of central NO synthase by NO₂Arg may facilitate studies of the physiologic function of NO as a neuronal messenger.

Original language	English (US)
Pages (from-to)	1136-1141
Number of pages	6
Journal	Biochemical and Biophysical Research Communications
Volume	176
Issue number	3
DOIs	https://doi.org/10.1016/0006-291X(91)90403-T
State	Published - May 15 1991

ASJC Scopus subject areas

Biophysics
Biochemistry
Molecular Biology
Cell Biology

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10.1016/0006-291X(91)90403-T

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title = "Nitric oxide synthase: Irreversible inhibition by L-NG-Nitroarginine in brain in vitro and in vivo",

abstract = "Inhibition of nitric oxide (NO) synthase activity by L-NG-Nitroarginine (NO2Arg) in brain preparations is not reversed by dialysis and is enhanced by prolonged preincubation of NO2Arg with the enzyme. By contrast, the weaker inhibition by NO2Arg of macrophage NO synthase is fully reversible. NO2Arg inhibits NO synthase activity in the brain after i.p. administration of 5 or 50 mg/kg. This in vivo inhibition also appears to be irreversible. The potent in vivo inhibition of central NO synthase by NO2Arg may facilitate studies of the physiologic function of NO as a neuronal messenger.",

author = "Dwyer, {Mary A.} and Bredt, {David S.} and Snyder, {Solomon H.}",

note = "Funding Information: We thank Balasubramanian for valuable advice. Supported by USPHS grants MH-18501 and DA-00266, Research Scientist Award DA0074 to S.H.S., Training Grant GM-07309 to D.S.M. and contract DA-271-90-7408 as well as a grant of the International Life Sciences Institute and a gift from Bristol-Myers-Squibb.",

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doi = "10.1016/0006-291X(91)90403-T",

language = "English (US)",

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T2 - Irreversible inhibition by L-NG-Nitroarginine in brain in vitro and in vivo

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AU - Bredt, David S.

AU - Snyder, Solomon H.

N1 - Funding Information: We thank Balasubramanian for valuable advice. Supported by USPHS grants MH-18501 and DA-00266, Research Scientist Award DA0074 to S.H.S., Training Grant GM-07309 to D.S.M. and contract DA-271-90-7408 as well as a grant of the International Life Sciences Institute and a gift from Bristol-Myers-Squibb.

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Y1 - 1991/5/15

N2 - Inhibition of nitric oxide (NO) synthase activity by L-NG-Nitroarginine (NO2Arg) in brain preparations is not reversed by dialysis and is enhanced by prolonged preincubation of NO2Arg with the enzyme. By contrast, the weaker inhibition by NO2Arg of macrophage NO synthase is fully reversible. NO2Arg inhibits NO synthase activity in the brain after i.p. administration of 5 or 50 mg/kg. This in vivo inhibition also appears to be irreversible. The potent in vivo inhibition of central NO synthase by NO2Arg may facilitate studies of the physiologic function of NO as a neuronal messenger.

AB - Inhibition of nitric oxide (NO) synthase activity by L-NG-Nitroarginine (NO2Arg) in brain preparations is not reversed by dialysis and is enhanced by prolonged preincubation of NO2Arg with the enzyme. By contrast, the weaker inhibition by NO2Arg of macrophage NO synthase is fully reversible. NO2Arg inhibits NO synthase activity in the brain after i.p. administration of 5 or 50 mg/kg. This in vivo inhibition also appears to be irreversible. The potent in vivo inhibition of central NO synthase by NO2Arg may facilitate studies of the physiologic function of NO as a neuronal messenger.

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Nitric oxide synthase: Irreversible inhibition by L-N^G-Nitroarginine in brain in vitro and in vivo

Abstract

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