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https://doi.org/10.2478/acph-2023-0004

The opposite effect of convulsant drugs on neuronal and endothelial nitric oxide synthase – A possible explanation for the dual proconvulsive/anticonvulsive action of nitric oxide

LOURDES A. VEGA RASGADO ; Laboratorio 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. 11340 Ciudad de México, México
EVA RAMÓN-GALLEGOS ; Laboratorio de Citopatología Ambiental, Departamento de Morfología, Escuela nacional de Ciencias Biológicas, Instituto Politécnico Nacional, Calle Wilfrido Massieu esquina Cerrada Manuel Stampa, Colonia Zacatenco, C.P. 07738 Ciudad de México, México
LORENA RODRÍGUEZ-PÁEZ RODRÍGUEZ-PÁEZ ; Laboratorio de Bioquímica Farmacológica, 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. 11340 Ciudad de México, México
VERÓNICA ALCÁNTARA-FARFÁN ; Laboratorio de Bioquímica Farmacológica, 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. 11340 Ciudad de México, México

Sažetak

Nitric oxide (NO) participates in processes such as endothelium-dependent vasodilation and neurotransmission/neuromodulation. The role of NO in epilepsy is controversial, attributing it to anticonvulsant but also proconvulsant properties. Clarification of this dual effect of NO might lead to the development of new antiepileptic drugs. Previous results in our laboratory indicated that this contradictory role of NO in seizures could depend on the nitric oxide synthase (NOS) isoform involved, which could play opposite roles in epileptogenesis, one of them being proconvulsant but the other anticonvulsant. The effect of convulsant drugs on neuronal NO (nNO) and endothelial NO (eNO) levels was investigated. Considering the distribution of neuronal and endothelial NOS in neurons and astrocytes, resp., primary cultures of neurons and astrocytes were used as a study model. The effects of convulsant drugs pentylenetetrazole, thiosemicarbazide, 4-aminopyridine and bicuculline on NO levels were studied, using a spectrophotometric method. Their effects on NO levels in neurons and astrocytes depend on the concentration and time of treatment. These convulsant drugs caused an increase in nNO, but a decrease in eNO was proportional to the duration of treatment in both cases. Apparently, nNO possesses convulsant properties mediated by its effect on the glutamatergic and GABAergic systems, probably through GABAA receptors. Anticonvulsant properties of eNO may be the consequence of its effect on endothelial vasodilation and its capability to induce angiogenesis. Described effects last as seizures do. Considering the limitations of these kinds of studies and the unexplored influence of inducible NO, further investigations are required.

Ključne riječi

epilepsy; nitric oxide; seizures; endothelial nitric oxide; neuronal nitric oxide

Hrčak ID:

281780

URI

https://hrcak.srce.hr/281780

Datum izdavanja:

31.3.2023.

Posjeta: 720 *