<abstract xmlns="http://www.w3.org/1999/xhtml"><p>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 (<sc>l</sc>-arginine) and inhibitors (Nω-nitro-<sc>l</sc>-arginine methyl ester, 7-nitroindazole) of NO synthase (NOS) on GABA-T activity and GABA levels <italic>in vitro</italic> and <italic>ex vivo</italic> were analyzed. <italic>In vitro</italic> NO diminished GABA-T activity and increased GABA. <italic>Ex vivo</italic> 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.</p></abstract>

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.

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

Departamento de Bioquímica, Escuela Nacional de Ciencias Biológicas, Instituto Politécnico Nacional Carpio y Plan de Ayala S/N

Laboratorio de Investigación Integral Cardiometabólica

Sección de Posgrado e Investigación, Escuela Superior de Medicina, Instituto Politécnico Nacional

Acta Pharmaceutica

This work is licensed under the Creative Commons Attribution-NonCommercial-NoDerivatives 3.0 License.

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...

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

Published Online: Jul 04, 2018

Page range: 349 - 359

Accepted: Feb 12, 2018

DOI: https://doi.org/10.2478/acph-2018-0022

Keywords
nitric oxide, GABA-transaminase, GABA, seizures

© 2018 Lourdes A. Vega Rasgado et al., published by Sciendo

This work is licensed under the Creative Commons Attribution-NonCommercial-NoDerivatives 3.0 License.

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

Published Online: Jul 04, 2018

Page range: 349 - 359

Accepted: Feb 12, 2018

DOI: https://doi.org/10.2478/acph-2018-0022

Keywordsnitric oxide, GABA-transaminase, GABA, seizures

© 2018 Lourdes A. Vega Rasgado et al., published by Sciendo

This work is licensed under the Creative Commons Attribution-NonCommercial-NoDerivatives 3.0 License.

Keywords
nitric oxide, GABA-transaminase, GABA, seizures