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Acta Pharmaceutica, Vol. 68 No. 3, 2018.

Original scientific paper

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

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

LOURDES A. VEGA RASGADO ; Laboratorio de Neuroquímica, Departamento de Bioquímica, Escuela Nacional de Ciencias Biológicas, Instituto Politécnico NacionalxxCarpio y Plan de Ayala S/N, Colonia Casco de Santo Tomás, C.P. 11340 Ciudad de México, México
GUILLERMO CEBALLOS REYES ; Laboratorio de Investigación Integral Cardiometabólica, Sección de Posgrado e Investigación, Escuela Superior de MedicinaxxInstituto Politécnico Nacional. Plan de San Luis y Díaz Mirón, Colonia Casco de Santo Tomás, C.P. 11340, Ciudad de México, México
FERNANDO VEGA DÍAZ ; Laboratorio de Neuroquímica, Departamento de Bioquímica, Escuela Nacional de Ciencias Biológicas, Instituto Politécnico NacionalxxCarpio y Plan de Ayala S/N, Colonia Casco de Santo Tomás, C.P. 11340 Ciudad de México, México

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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.

Keywords

nitric oxide; GABA-transaminase; GABA; seizures

Hrčak ID:

195715

URI

https://hrcak.srce.hr/195715

Publication date:

30.9.2018.

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