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Xanthurenic acid distribution, transport, accumulation and release in the rat brain
Author(s) -
Gobaille Serge,
Kemmel Véronique,
Brumaru Daniel,
Dugave Christophe,
Aunis Dominique,
Maitre Michel
Publication year - 2008
Publication title -
journal of neurochemistry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.75
H-Index - 229
eISSN - 1471-4159
pISSN - 0022-3042
DOI - 10.1111/j.1471-4159.2008.05219.x
Subject(s) - kynurenic acid , neurotransmission , chemistry , extracellular , biochemistry , biophysics , microbiology and biotechnology , biology , glutamate receptor , receptor
Tryptophan metabolism through the kynurenine pathway leads to several neuroactive compounds, including kynurenic and picolinic acids. Xanthurenic acid (Xa) has been generally considered as a substance with no physiological role but possessing toxic and apoptotic properties. In the present work, we present several findings which support a physiological role for endogenous Xa in synaptic signalling in brain. This substance is present in micromolar amounts in most regions of the rat brain with a heterogeneous distribution. An active vesicular synaptic process inhibited by bafilomycin and nigericin accumulates xanthurenate into pre‐synaptic terminals. A neuronal transport, partially dependant on adenosine 5′‐triphosphate (ATP), sodium and chloride ions exists in NCB‐20 neurons which could participate in the clearance of extracellular xanthurenate. Both transports (neuronal and vesicular) are greatly enhanced by the presence of micromolar amounts of zinc ions. Finally, electrical in vivo stimulation of A10‐induced Xa release in the extracellular spaces of the rat prefrontal cortex. This phenomenon is reproduced by veratrine, K + ions and blocked by EGTA and tetrodotoxin. These results strongly argue for a role for Xa in neurotransmission/neuromodulation in the rat brain, thus providing the existence of specific Xa receptors.