Xanthurenic Acid Activates mGlu2/3 Metabotropic Glutamate Receptors and is a Potential Trait Marker for Schizophrenia
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Author
Fazio, Francesco
Lionetto, Luana
Curto, Martina
Iacovelli, Luisa
Zappulla, Cristina
Ulivieri, Martina
Napoletano, Flavia
Capi, Matilde
Corigliano, Valentina
Scaccianoce, Sergio
Caruso, Alessandra
Miele, Jessica
De Fusco, Antonio
Di Menna, Luisa
Comparelli, Anna
De Carolis, Antonella
Gradini, Roberto
Nisticò, Robert
De Blasi, Antonio
Girardi, Paolo
Bruno, Valeria
Battaglia, Giuseppe
Nicoletti, Ferdinando
Simmaco, Maurizio
Note: Order does not necessarily reflect citation order of authors.
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https://doi.org/10.1038/srep17799Metadata
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Fazio, F., L. Lionetto, M. Curto, L. Iacovelli, M. Cavallari, C. Zappulla, M. Ulivieri, et al. 2015. “Xanthurenic Acid Activates mGlu2/3 Metabotropic Glutamate Receptors and is a Potential Trait Marker for Schizophrenia.” Scientific Reports 5 (1): 17799. doi:10.1038/srep17799. http://dx.doi.org/10.1038/srep17799.Abstract
The kynurenine pathway of tryptophan metabolism has been implicated in the pathophysiology of psychiatric disorders, including schizophrenia. We report here that the kynurenine metabolite, xanturenic acid (XA), interacts with, and activates mGlu2 and mGlu3 metabotropic glutamate receptors in heterologous expression systems. However, the molecular nature of this interaction is unknown, and our data cannot exclude that XA acts primarily on other targets, such as the vesicular glutamate transporter, in the CNS. Systemic administration of XA in mice produced antipsychotic-like effects in the MK-801-induced model of hyperactivity. This effect required the presence of mGlu2 receptors and was abrogated by the preferential mGlu2/3 receptor antagonist, LY341495. Because the mGlu2 receptor is a potential drug target in the treatment of schizophrenia, we decided to measure serum levels of XA and other kynurenine metabolites in patients affected by schizophrenia. Serum XA levels were largely reduced in a large cohort of patients affected by schizophrenia, and, in patients with first-episode schizophrenia, levels remained low after 12 months of antipsychotic medication. As opposed to other kynurenine metabolites, XA levels were also significantly reduced in first-degree relatives of patients affected by schizophrenia. We suggest that lowered serum XA levels might represent a novel trait marker for schizophrenia.Other Sources
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