The Effect of Systemic Nitroglycerin Administration on the Kynurenine Pathway in the Rat
Authors: Eleon√≥ra Spekker
G√°bor Veres
√Årp√°d P√°rdutz
L√°szl√≥ V√©csei
Annam√°ria Fejes-Szab√≥
Zsuzsanna Boh√°r
Attila Bajtai
G√°bor Nagy-Gr√≥cz
Klaudia F Laborc
D√©nes Z√°dori
Journal: Frontiers in neurology (2017)
Discipline: CLINICAL MEDICINE
Keywords: kynurenic acid; kynurenine pathway; l-kynurenine; migraine; nitroglycerin.
Affiliations: MTA-SZTE Neuroscience Research Group, University of Szeged, Szeged, Hungary., Faculty of Health Sciences and Social Studies, University of Szeged, Szeged, Hungary., Department of Neurology, Faculty of Medicine, Albert Szent-Gy√∂rgyi Clinical Center, University of Szeged, Szeged, Hungary.

Abstract:  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. 

Retracted: No

PubPeer comments:
 Compare Fig. 3 and Fig. 5 GAPDH https: imgur.com a FcKBAIM , 
 Thank you for pointing out an issue in the presentation of the household protein in figure 3 and 5. After checking the original logs films we are sure that the results published in the manuscript are unaffected. We are grateful for your vigilance. , 
 #2 I thank the authors for their reply. To be clear, are you saying you agree with the reader in #1 that the two GAPDH images erroneously share the same source? If yes, are you intending to prepare a correction? , 
 As mentioned earlier, we checked the lane densities on the films again and these data are OK. For the publication, the representative figures were prepared later and we cannot rule out, that you are right concerning the household protein. Although we have taken that in consideration - but since there is no impact of any kind on the numerical data and the conclusion of the MS - we dont intend to prepare a correction. Nevertheless we will modify our manuscript processing in our lab to reduce the possibility of such errors. ,