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
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 dev...
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| Format: | Article |
| Language: | English |
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Sciendo
2023-03-01
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| Series: | Acta Pharmaceutica |
| Subjects: | |
| Online Access: | https://doi.org/10.2478/acph-2023-0004 |
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| author | Vega Rasgado Lourdes A. Ramón-Gallegos Eva Rodríguez-Páez Lorena Alcántara-Farfán Verónica |
| author_facet | Vega Rasgado Lourdes A. Ramón-Gallegos Eva Rodríguez-Páez Lorena Alcántara-Farfán Verónica |
| author_sort | Vega Rasgado Lourdes A. |
| collection | DOAJ |
| description | 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. |
| first_indexed | 2024-04-10T17:14:08Z |
| format | Article |
| id | doaj.art-980f6410db894bc0b2feece23340be7f |
| institution | Directory Open Access Journal |
| issn | 1846-9558 |
| language | English |
| last_indexed | 2024-04-10T17:14:08Z |
| publishDate | 2023-03-01 |
| publisher | Sciendo |
| record_format | Article |
| series | Acta Pharmaceutica |
| spelling | doaj.art-980f6410db894bc0b2feece23340be7f2023-02-05T18:30:18ZengSciendoActa Pharmaceutica1846-95582023-03-01731597410.2478/acph-2023-0004The opposite effect of convulsant drugs on neuronal and endothelial nitric oxide synthase – A possible explanation for the dual proconvulsive/anticonvulsive action of nitric oxideVega Rasgado Lourdes A.0Ramón-Gallegos Eva1Rodríguez-Páez Lorena2Alcántara-Farfán Verónica3Laboratorio 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, MéxicoLaboratorio 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, MéxicoLaboratorio 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, MéxicoLaboratorio 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, MéxicoNitric 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.https://doi.org/10.2478/acph-2023-0004epilepsynitric oxideseizuresendothelial nitric oxideneuronal nitric oxide |
| spellingShingle | Vega Rasgado Lourdes A. Ramón-Gallegos Eva Rodríguez-Páez Lorena Alcántara-Farfán Verónica 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 Acta Pharmaceutica epilepsy nitric oxide seizures endothelial nitric oxide neuronal nitric oxide |
| title | 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 |
| title_full | 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 |
| title_fullStr | 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 |
| title_full_unstemmed | 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 |
| title_short | 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 |
| title_sort | opposite effect of convulsant drugs on neuronal and endothelial nitric oxide synthase a possible explanation for the dual proconvulsive anticonvulsive action of nitric oxide |
| topic | epilepsy nitric oxide seizures endothelial nitric oxide neuronal nitric oxide |
| url | https://doi.org/10.2478/acph-2023-0004 |
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