Acta Pharm. 68 (2018) 349-359

Original research paper

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

LOURDES A. VEGA RASGADO, GUILLERMO CEBALLOS REYES and FERNANDO VEGA DÍAZ

¹ 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

² 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

Accepted February 12, 2018

Published online March 16, 2018

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