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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2018-09-01
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Series: | Acta Pharmaceutica |
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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. |
format | Article |
id | doaj-art-7c9017f2674e4d43a3c52683ca16227f |
institution | Kabale University |
issn | 1846-9558 |
language | English |
publishDate | 2018-09-01 |
publisher | Sciendo |
record_format | Article |
series | Acta Pharmaceutica |
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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