Role of nitric oxide synthase on brain GABA transaminase activity and GABA levels

In an attempt to clarify the controversial role of nitric oxide (NO) in seizures, the effects of NO on brain GABA transaminase (GABA-T) activity and GABA levels were investigated. To this aim, the effects of the substrate (l-arginine) and inhibitors (Nω-nitro-l-arginine methyl ester, 7-nitroindazole...

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Main Authors: Vega Rasgado Lourdes A., Reyes Guillermo Ceballos, Vega Díaz Fernando
Format: Article
Language:English
Published: Sciendo 2018-09-01
Series:Acta Pharmaceutica
Subjects:
Online Access:https://doi.org/10.2478/acph-2018-0022
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author Vega Rasgado Lourdes A.
Reyes Guillermo Ceballos
Vega Díaz Fernando
author_facet Vega Rasgado Lourdes A.
Reyes Guillermo Ceballos
Vega Díaz Fernando
author_sort Vega Rasgado Lourdes A.
collection DOAJ
description In an attempt to clarify the controversial role of nitric oxide (NO) in seizures, the effects of NO on brain GABA transaminase (GABA-T) activity and GABA levels were investigated. To this aim, the effects of the substrate (l-arginine) and inhibitors (Nω-nitro-l-arginine methyl ester, 7-nitroindazole) of NO synthase (NOS) on GABA-T activity and GABA levels in vitro and ex vivo were analyzed. In vitro NO diminished GABA-T activity and increased GABA. Ex vivo NO modified GABA-T activity and GABA levels biphasically. Inhibition of endothelial and neuronal NOS (eNOS and nNOS) had opposite effects on GABA-T activity and GABA levels, even during seizures induced by pentylenetetrazole. Different effects of NO on GABA-T activity and on GABA levels, depending on the NOS isoform involved, may explain its contradictory role in seizures, the endothelial NOS acting as an anticonvulsant and the neuronal NOS as a proconvulsant. nNOS inhibitors may represent a new generation of antiepileptics.
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spelling doaj-art-7c9017f2674e4d43a3c52683ca16227f2025-02-02T12:01:39ZengSciendoActa Pharmaceutica1846-95582018-09-0168334935910.2478/acph-2018-0022acph-2018-0022Role of nitric oxide synthase on brain GABA transaminase activity and GABA levelsVega Rasgado Lourdes A.0Reyes Guillermo Ceballos1Vega Díaz Fernando2Laboratorio de Neuroquímica, Departamento de Bioquímica, Escuela Nacional de Ciencias Biológicas, Instituto Politécnico Nacional Carpio y Plan de Ayala S/N, Colonia Casco de Santo Tomás, C.P. 11340Ciudad de México, MéxicoLaboratorio de Investigación Integral Cardiometabólica, Sección de Posgrado e Investigación, Escuela Superior de Medicina, Instituto Politécnico Nacional. Plan de San Luis y Díaz Mirón Colonia Casco de Santo Tomás, C.P. 11340Ciudad de México, MéxicoLaboratorio de Neuroquímica, Departamento de Bioquímica, Escuela Nacional de Ciencias Biológicas, Instituto Politécnico Nacional Carpio y Plan de Ayala S/N, Colonia Casco de Santo Tomás, C.P. 11340Ciudad de México, MéxicoIn an attempt to clarify the controversial role of nitric oxide (NO) in seizures, the effects of NO on brain GABA transaminase (GABA-T) activity and GABA levels were investigated. To this aim, the effects of the substrate (l-arginine) and inhibitors (Nω-nitro-l-arginine methyl ester, 7-nitroindazole) of NO synthase (NOS) on GABA-T activity and GABA levels in vitro and ex vivo were analyzed. In vitro NO diminished GABA-T activity and increased GABA. Ex vivo NO modified GABA-T activity and GABA levels biphasically. Inhibition of endothelial and neuronal NOS (eNOS and nNOS) had opposite effects on GABA-T activity and GABA levels, even during seizures induced by pentylenetetrazole. Different effects of NO on GABA-T activity and on GABA levels, depending on the NOS isoform involved, may explain its contradictory role in seizures, the endothelial NOS acting as an anticonvulsant and the neuronal NOS as a proconvulsant. nNOS inhibitors may represent a new generation of antiepileptics.https://doi.org/10.2478/acph-2018-0022nitric oxidegaba-transaminasegabaseizures
spellingShingle Vega Rasgado Lourdes A.
Reyes Guillermo Ceballos
Vega Díaz Fernando
Role of nitric oxide synthase on brain GABA transaminase activity and GABA levels
Acta Pharmaceutica
nitric oxide
gaba-transaminase
gaba
seizures
title Role of nitric oxide synthase on brain GABA transaminase activity and GABA levels
title_full Role of nitric oxide synthase on brain GABA transaminase activity and GABA levels
title_fullStr Role of nitric oxide synthase on brain GABA transaminase activity and GABA levels
title_full_unstemmed Role of nitric oxide synthase on brain GABA transaminase activity and GABA levels
title_short Role of nitric oxide synthase on brain GABA transaminase activity and GABA levels
title_sort role of nitric oxide synthase on brain gaba transaminase activity and gaba levels
topic nitric oxide
gaba-transaminase
gaba
seizures
url https://doi.org/10.2478/acph-2018-0022
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AT reyesguillermoceballos roleofnitricoxidesynthaseonbraingabatransaminaseactivityandgabalevels
AT vegadiazfernando roleofnitricoxidesynthaseonbraingabatransaminaseactivityandgabalevels