RGD Reference Report - The Effect of Systemic Nitroglycerin Administration on the Kynurenine Pathway in the Rat. - Rat Genome Database

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The Effect of Systemic Nitroglycerin Administration on the Kynurenine Pathway in the Rat.

Authors: Nagy-Grócz, Gábor  Laborc, Klaudia F  Veres, Gábor  Bajtai, Attila  Bohár, Zsuzsanna  Zádori, Dénes  Fejes-Szabó, Annamária  Spekker, Eleonóra  Vécsei, László  Párdutz, Árpád 
Citation: Nagy-Grócz G, etal., Front Neurol. 2017 Jun 14;8:278. doi: 10.3389/fneur.2017.00278. eCollection 2017.
RGD ID: 13601983
Pubmed: PMID:28659861   (View Abstract at PubMed)
PMCID: PMC5469907   (View Article at PubMed Central)
DOI: DOI:10.3389/fneur.2017.00278   (Journal Full-text)

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.

Gene Ontology Annotations    

Biological Process

Objects Annotated

Genes (Rattus norvegicus)
Tdo2  (tryptophan 2,3-dioxygenase)

Additional Information