title: Cinnabarinic acid and xanthurenic acid: Two kynurenine metabolites that interact with metabotropic glutamate receptors.
abstract: Cinnabarinic and xanthurenic acids are kynurenine metabolites generated by oxidative dimerization of 3-hydroxyanthranilic acid and transamination of 3-hydroxykynurenine, respectively. Recent evidence suggests that both compounds can affect brain function and neurotransmission and interact with metabotropic glutamate (mGlu) receptors. Cinnabarinic acid behaves as an orthosteric agonist of mGlu4 receptors, whereas some of the in vitro and in vivo effects produced by xanthurenic acid appear to be mediated by the activation of mGlu2 and mGlu3 receptors. Cinnabarinic acid could play an important role in mechanisms of neuroinflammation acting as a linking bridge between the immune system and the CNS. Xanthurenic acid has potential implications in the pathophysiology of schizophrenia and is a promising candidate as a peripheral biomarker of the disorder. The action of cinnabarinic acid and xanthurenic acid may extend beyond the regulation of mGlu receptors and may involve several diverse molecular targets, such as the aryl hydrocarbon receptor for cinnabarinic acid and vesicular glutamate transporters for xanthurenic acid. The growing interest on these two metabolites of the kynurenine pathway may unravel new aspects in the complex interaction between tryptophan metabolism and brain function, and lead to the discovery of new potential targets for the treatment of neurological and psychiatric disorders. This article is part of the Special Issue entitled 'The Kynurenine Pathway in Health and Disease'.
authors.affiliation: I.R.C.C.S. Neuromed, Pozzilli, Italy. Electronic address: francesco_fazio@alice.it.
authors.forename: Francesco
authors.initials: F
authors.lastname: Fazio
authors.affiliation: Advanced Molecular Diagnostic, IDI-IRCCS, Rome, Italy.
authors.forename: Luana
authors.initials: L
authors.lastname: Lionetto
authors.affiliation: Department of Molecular Medicine, Sant'Andrea Medical Center, Sapienza University, Rome, Italy.
authors.forename: Martina
authors.initials: M
authors.lastname: Curto
authors.affiliation: Department of Physiology and Pharmacology, Sapienza University, Rome, Italy.
authors.forename: Luisa
authors.initials: L
authors.lastname: Iacovelli
authors.affiliation: St George's, University of London, UK.
authors.forename: Caroline S
authors.initials: CS
authors.lastname: Copeland
authors.affiliation: Neurexpert Ltd, Kemp House, City Road, London, EC1V 2NX, UK.
authors.forename: Stuart A
authors.initials: SA
authors.lastname: Neale
authors.affiliation: I.R.C.C.S. Neuromed, Pozzilli, Italy; Department of Physiology and Pharmacology, Sapienza University, Rome, Italy.
authors.forename: Valeria
authors.initials: V
authors.lastname: Bruno
authors.affiliation: I.R.C.C.S. Neuromed, Pozzilli, Italy.
authors.forename: Giuseppe
authors.initials: G
authors.lastname: Battaglia
authors.affiliation: UCL Institute of Ophthalmology, London, EC1V 9EL, UK.
authors.forename: Thomas E
authors.initials: TE
authors.lastname: Salt
authors.affiliation: I.R.C.C.S. Neuromed, Pozzilli, Italy; Department of Physiology and Pharmacology, Sapienza University, Rome, Italy.
authors.forename: Ferdinando
authors.initials: F
authors.lastname: Nicoletti
mesh_terms: D000818:Animals; D006801:Humans; D007737:Kynurenine / Q000378:metabolism*; D010078:Oxazines / Q000378:metabolism* / Q000494:pharmacology; D018094:Receptors, Metabotropic Glutamate / Q000378:metabolism*; D014977:Xanthurenates / Q000378:metabolism* / Q000494:pharmacology
chemical_list: D010078:Oxazines; D018094:Receptors, Metabotropic Glutamate; D014977:Xanthurenates; D007737:Kynurenine; C028330:xanthurenic acid; C000483:cinnabarinic acid
keywords: Cinnabarinic acid; Metabotropic glutamate receptors; Neuroinflammation; Schizophrenia; Xanthurenic acid