The Effect of Systemic Nitroglycerin Administration on the Kynurenine Pathway in the Rat
The primary headache disorders include migraine, which is one of the most frequent neurological disorders, which influences more than 14% of the whole population. Despite the research efforts, its exact pathomechanism is not fully revealed, but evidence points to the role of glutamate and its recept...
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| Format: | Article |
| Language: | English |
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Frontiers Media S.A.
2017-06-01
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| Series: | Frontiers in Neurology |
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| Online Access: | http://journal.frontiersin.org/article/10.3389/fneur.2017.00278/full |
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| author | Gábor Nagy-Grócz Gábor Nagy-Grócz Klaudia F. Laborc Gábor Veres Attila Bajtai Zsuzsanna Bohár Zsuzsanna Bohár Dénes Zádori Annamária Fejes-Szabó Eleonóra Spekker László Vécsei László Vécsei Árpád Párdutz |
| author_facet | Gábor Nagy-Grócz Gábor Nagy-Grócz Klaudia F. Laborc Gábor Veres Attila Bajtai Zsuzsanna Bohár Zsuzsanna Bohár Dénes Zádori Annamária Fejes-Szabó Eleonóra Spekker László Vécsei László Vécsei Árpád Párdutz |
| author_sort | Gábor Nagy-Grócz |
| collection | DOAJ |
| description | The primary headache disorders include migraine, which is one of the most frequent neurological disorders, which influences more than 14% of the whole population. Despite the research efforts, its exact pathomechanism is not fully revealed, but evidence points to the role of glutamate and its receptors. Kynurenic acid is an endogenous glutamate receptor antagonist produced by the kynurenine pathway (KP). Tryptophan 2,3-dioxygenase (TDO) and indoleamine 2,3-dioxygenase (IDO) convert l-tryptophan to N-formyl-l-kynurenine, to be further transformed to l-kynurenine. Kynurenine aminotransferase-II (KAT-II), l-kynurenine hydrolase (KYNU), and l-kynurenine 3-monooxygenase (KMO) are key enzymes in the later steps of the KP. Nitroglycerin (NTG) administration serves as both human and animal model of migraine, causing the activation and sensitization in the trigeminal system. A previous study demonstrated a reduction of KAT-II expression following NTG administration in animals. The goal of current tests was to identify the potential modulatory effect of NTG on other metabolizing enzymes of the KP in the caudal trigeminal nucleus (TNC) of rats. Four hours following the intraperitoneal injection of NTG (10 mg/kg), the rats were perfused transcardially and the TNC was extracted for Western blotting. Western blot studies revealed that the expression of TDO2, IDO1, KYNU, and KMO decreased in the TNC. The results demonstrated that NTG is able to downregulate the KP, with a potential influence on the glutamatergic system as well, contributing to the development of trigeminal activation and sensitization in animals. |
| first_indexed | 2024-04-13T18:14:38Z |
| format | Article |
| id | doaj.art-e45dae2f4fea41e1914a6602d80f6f65 |
| institution | Directory Open Access Journal |
| issn | 1664-2295 |
| language | English |
| last_indexed | 2024-04-13T18:14:38Z |
| publishDate | 2017-06-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Neurology |
| spelling | doaj.art-e45dae2f4fea41e1914a6602d80f6f652022-12-22T02:35:43ZengFrontiers Media S.A.Frontiers in Neurology1664-22952017-06-01810.3389/fneur.2017.00278260889The Effect of Systemic Nitroglycerin Administration on the Kynurenine Pathway in the RatGábor Nagy-Grócz0Gábor Nagy-Grócz1Klaudia F. Laborc2Gábor Veres3Attila Bajtai4Zsuzsanna Bohár5Zsuzsanna Bohár6Dénes Zádori7Annamária Fejes-Szabó8Eleonóra Spekker9László Vécsei10László Vécsei11Árpád Párdutz12MTA-SZTE Neuroscience Research Group, University of Szeged, Szeged, HungaryFaculty of Health Sciences and Social Studies, University of Szeged, Szeged, HungaryDepartment of Neurology, Faculty of Medicine, Albert Szent-Györgyi Clinical Center, University of Szeged, Szeged, HungaryMTA-SZTE Neuroscience Research Group, University of Szeged, Szeged, HungaryDepartment of Neurology, Faculty of Medicine, Albert Szent-Györgyi Clinical Center, University of Szeged, Szeged, HungaryMTA-SZTE Neuroscience Research Group, University of Szeged, Szeged, HungaryDepartment of Neurology, Faculty of Medicine, Albert Szent-Györgyi Clinical Center, University of Szeged, Szeged, HungaryDepartment of Neurology, Faculty of Medicine, Albert Szent-Györgyi Clinical Center, University of Szeged, Szeged, HungaryMTA-SZTE Neuroscience Research Group, University of Szeged, Szeged, HungaryDepartment of Neurology, Faculty of Medicine, Albert Szent-Györgyi Clinical Center, University of Szeged, Szeged, HungaryMTA-SZTE Neuroscience Research Group, University of Szeged, Szeged, HungaryDepartment of Neurology, Faculty of Medicine, Albert Szent-Györgyi Clinical Center, University of Szeged, Szeged, HungaryDepartment of Neurology, Faculty of Medicine, Albert Szent-Györgyi Clinical Center, University of Szeged, Szeged, HungaryThe primary headache disorders include migraine, which is one of the most frequent neurological disorders, which influences more than 14% of the whole population. Despite the research efforts, its exact pathomechanism is not fully revealed, but evidence points to the role of glutamate and its receptors. Kynurenic acid is an endogenous glutamate receptor antagonist produced by the kynurenine pathway (KP). Tryptophan 2,3-dioxygenase (TDO) and indoleamine 2,3-dioxygenase (IDO) convert l-tryptophan to N-formyl-l-kynurenine, to be further transformed to l-kynurenine. Kynurenine aminotransferase-II (KAT-II), l-kynurenine hydrolase (KYNU), and l-kynurenine 3-monooxygenase (KMO) are key enzymes in the later steps of the KP. Nitroglycerin (NTG) administration serves as both human and animal model of migraine, causing the activation and sensitization in the trigeminal system. A previous study demonstrated a reduction of KAT-II expression following NTG administration in animals. The goal of current tests was to identify the potential modulatory effect of NTG on other metabolizing enzymes of the KP in the caudal trigeminal nucleus (TNC) of rats. Four hours following the intraperitoneal injection of NTG (10 mg/kg), the rats were perfused transcardially and the TNC was extracted for Western blotting. Western blot studies revealed that the expression of TDO2, IDO1, KYNU, and KMO decreased in the TNC. The results demonstrated that NTG is able to downregulate the KP, with a potential influence on the glutamatergic system as well, contributing to the development of trigeminal activation and sensitization in animals.http://journal.frontiersin.org/article/10.3389/fneur.2017.00278/fullmigrainenitroglycerinkynurenic acidl-kynureninekynurenine pathway |
| spellingShingle | Gábor Nagy-Grócz Gábor Nagy-Grócz Klaudia F. Laborc Gábor Veres Attila Bajtai Zsuzsanna Bohár Zsuzsanna Bohár Dénes Zádori Annamária Fejes-Szabó Eleonóra Spekker László Vécsei László Vécsei Árpád Párdutz The Effect of Systemic Nitroglycerin Administration on the Kynurenine Pathway in the Rat Frontiers in Neurology migraine nitroglycerin kynurenic acid l-kynurenine kynurenine pathway |
| title | The Effect of Systemic Nitroglycerin Administration on the Kynurenine Pathway in the Rat |
| title_full | The Effect of Systemic Nitroglycerin Administration on the Kynurenine Pathway in the Rat |
| title_fullStr | The Effect of Systemic Nitroglycerin Administration on the Kynurenine Pathway in the Rat |
| title_full_unstemmed | The Effect of Systemic Nitroglycerin Administration on the Kynurenine Pathway in the Rat |
| title_short | The Effect of Systemic Nitroglycerin Administration on the Kynurenine Pathway in the Rat |
| title_sort | effect of systemic nitroglycerin administration on the kynurenine pathway in the rat |
| topic | migraine nitroglycerin kynurenic acid l-kynurenine kynurenine pathway |
| url | http://journal.frontiersin.org/article/10.3389/fneur.2017.00278/full |
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