Kynurenine aminotransferase in the supratentorial dura mater of the rat: effect of stimulation of the trigeminal ganglion

Knyihár‐Csillik, Elizabeth; Chadaide, Zoltán; Okuno, Etsuo; Krisztin-Péva, Beáta; Toldi, József; Varga, Csaba; Molnár, Árpád; Csillik, B.; Vécsei, László

doi:10.1016/j.expneurol.2003.12.001

Cited by 36 publications

(35 citation statements)

References 23 publications

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“…Assuming species cross-reactivity, the anti-KAT II antibody used in the present study should serve as a useful tool to explore such possible abnormalities in both animals and humans. Such future studies should also include comparisons with KAT I, a second astrocytic KYNA-forming brain enzyme (Roberts et al, 1992), which plays only a minor role in KYNA physiology (Guidetti et al, 1997) but appears to be more prominently involved in brain pathology (Cooper, 2004;Csillik et al, 2002;Knyihar-Csillik et al, 2004;Kwok et al, 2002).…”

Section: Discussionmentioning

confidence: 98%

Astrocytic localization of kynurenine aminotransferase II in the rat brain visualized by immunocytochemistry

Guidetti

Hoffman

Meléndez-Ferro

et al. 2006

Glia

129

111

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Kynurenic acid (KYNA), a metabolite of the kynurenine pathway of tryptophan degradation, is a neuroinhibitory agent present in the mammalian brain. Endogenous KYNA preferentially affects the alpha7 nicotinic acetylcholine (alpha7nACh) receptor and, possibly, the glycine co-agonist (glycineB) site of the NMDA receptor. Functionally relevant fluctuations in brain KYNA occur under both physiological and pathological conditions, affecting cholinergic and glutamatergic neurotransmission. Kynurenine aminotransferase II (KAT II), the major biosynthetic enzyme of KYNA in the rat brain, catalyzes the irreversible formation of KYNA from its immediate bioprecursor, kynurenine. We now purified rat kidney KAT II to homogeneity, generated a polyclonal rabbit anti-rat KAT II antibody, and purified the antibody using routine biochemical methods. The antibody selectively recognized KAT II by Western blot analysis and in immunotitration experiments. Used for immunocytochemistry, the antibody revealed discrete, specific staining of KAT II-positive astrocyte-like cells throughout the adult rat brain. The presence of KAT II in astrocytes was confirmed by double fluorescence immunostaining with an antibody against the astrocyte-specific marker glial fibrillary acidic protein (GFAP). No specific labeling was detected in neurons or microglia. However, KAT II-positive astrocytes were intimately associated with select neuron populations, supporting a neuromodulatory role of KYNA. Intense staining was frequently seen around brain capillaries, with astrocytic end feet contacting the capillary wall. This may explain the rapid access of blood-derived kynurenine to KAT II-containing astrocytes. The new anti-KAT II antibody should be useful in the further elucidation of the presumed role of KYNA in brain physiology and pathology.

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Section: Discussionmentioning

confidence: 98%

Astrocytic localization of kynurenine aminotransferase II in the rat brain visualized by immunocytochemistry

Guidetti

Hoffman

Meléndez-Ferro

et al. 2006

Glia

129

111

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“…Knyihár-Csillik and colleagues found that after electrical stimulation of the trigeminal ganglion, a well characterized model of trigeminal activation and dural neurogenic inflammation, KAT immunoreactivity of the cerebral dura mater decreased in rats [131]. These results suggest that endogenous KYNA synthesis in the dura may contribute to the modulation of NMDA receptor function.…”

Section: Kynurenines In Migrainementioning

confidence: 84%

Tryptophan Catabolites and Migraine

Bohár

Párdutz

Vécsei

2016

CPD

Self Cite

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Abstract:Migraine is a highly disabling neurological condition affecting around 15% of the population worldwide.Decades of intensive research shed some light on diseases pathomechanism, but information is still missing about the initiation of the attack. In the past century, serotonin emerged as the main target of both basic and therapeutic research. As a result, the triptans, the only approved migraine specific drugs were developed. The involvement of glutamatergic mechanism in migraine headache development such as cortical hyperexcitability, and cortical spreading depression as the pathological correlate of migraine aura called the attention to the kynurenine pathway in migraine pathomechanism. The serotonin and kynurenine pathways are closely connected, as they both are the metabolic routes of the amino acid tryptophan. Kynurenine catabolites are important participants in glutamatergic neurotransmission, regulation also nociceptive processing of the trigeminal system. The current work attempts to collect recent data on both serotonin and kynurenine research related to migraine and emphasizes the importance of further research on this topic.

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“…In a model of electrical stimulation of the rat TG, immunoreactivity of kynurenine aminotransferase (KAT), the synthesizing enzyme of KYNA, was reported to be decreased in dural mast cells, macrophages, and Schwann cells [135]. A possible site of action of KYNA might be the TG [134,136].…”

Section: Kynurenic Acidmentioning

confidence: 99%

Migraine, Neurogenic Inflammation, Drug Development - Pharmacochemical Aspects

Lukács

Tajti

Fülöp

et al. 2017

CMC

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Abstract:Background: Migraine is a primary headache disorder. Despite numerous studies conducted with the aim to understand the pathophysiology of migraine, several aspects are still unclear. The trigeminovascular system plays a key role. Neurogenic inflammation is presumed to be an important factor in migraine pathophysiology, mediated by the activation of primary neurons, leading to the release of various pro-inflammatory neuropeptides and neurotransmitters such as Calcitonin Gene-Related Peptide (CGRP), substance P (SP), and vasoactive intestinal peptide (VIP). Nitric oxide (NO), Pituitary adenylate cyclase-activating polypeptide (PACAP) and Glutamate (Glu) also play an important role in the modulation of inflammatory mechanisms. Objective: To review the literature focusing on novel therapeutic targets in migraine, related to neurogenic inflammation. Method: A systematic literature search in the database of PUBMED was conducted regarding therapeutic strategies in migraine, focusing on substances and cytokines released during neurogenic inflammation, published in January 2017. Results: Ongoing phase III clinical studies with monoclonal antibodies against CGRP and CGRP receptors offer promising novel aspects for migraine treatment. Preclinical and clinical studies targeting SP and nitric oxide synthase (NOS) were all terminated with no significant result compared to placebo. New promising therapeutic goal could be PACAP and its receptor (PAC 1 ), and kynurenic acid (KYNA) analogues. Conclusion: Current migraine treatment offers pain relief only for a small proportion of migraine patients and might not be adequate for patients with cardiovascular comorbidity due to side effects. Better understanding of migraine pathophysiology might, therefore, lead to novel therapeutic lines both in migraine attack treatment and prophylaxis.

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Kynurenine aminotransferase in the supratentorial dura mater of the rat: effect of stimulation of the trigeminal ganglion

Cited by 36 publications

References 23 publications

Astrocytic localization of kynurenine aminotransferase II in the rat brain visualized by immunocytochemistry

Astrocytic localization of kynurenine aminotransferase II in the rat brain visualized by immunocytochemistry

Tryptophan Catabolites and Migraine

Migraine, Neurogenic Inflammation, Drug Development - Pharmacochemical Aspects

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