Enhanced neuronal damage by co-administration of quinolinic acid and free radicals, and protection by adenosine A2A receptor antagonists

British Journal of Pharmacology
W M H Behan, Trevor W Stone

Abstract

1. Quinolinic acid may be an important endogenous excitotoxin, but its concentrations in brain are low. We have therefore attempted to determine whether its neurotoxicity can be increased by the simultaneous presence of free radicals. 2. Quinolinic acid was injected into the hippocampus of anaesthetized rats at doses of 40 and 80 nmols which produced little neuronal loss, and 120 nmols which produced over 90% neuronal loss. 3. A mixture of xanthine and xanthine oxidase, a known source of free radical reactive oxygen species, also generated little damage alone, but killed over 80% of CA1 neurons when combined with 80 nmols of quinolinic acid. Similarly, the nitric oxide donor S-nitroso-N-acetylpenicillamine (SNAP) potentiated the damage produced by quinolinic acid. 4. The glutamate antagonist 5,7-dichlorokynurenic acid prevented the damage produced by 120 nmols of quinolinic acid, but not that produced by quinolinic acid plus xanthine/xanthine oxidase, indicating that damage was not simply the result of free radical enhancement of NMDA receptor activation. 5. Three chemically dissimilar antagonists at adenosine A(2A) receptors prevented the damage caused by quinolinic acid and xanthine/xanthine oxidase or by quinolinic acid plus...Continue Reading

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Citations

Jan 11, 2005·Neurotoxicity Research·Gilles J GuilleminBruce J Brew
Apr 23, 2009·Neurotoxicity Research·Krystyna GołembiowskaKatarzyna Kamińska
Jun 3, 2009·Naunyn-Schmiedeberg's Archives of Pharmacology·Malika El YacoubiJean-Marie Vaugeois
Aug 12, 2005·Journal of Neurochemistry·Josep SauraJoan Serratosa
Apr 15, 2005·Neurological Research·Trevor W Stone
Jun 21, 2011·Parkinson's Disease·Anna ZingerGilles J Guillemin
Sep 29, 2009·Neurochemistry International·Hélio Vitoriano NobreGlauce Socorro de Barros Viana
Aug 2, 2007·Medicinal Research Reviews·Maykel Pérez GonzálezMarta Teijeira
Dec 3, 2008·The European Journal of Neuroscience·Alexandra L Ferguson, Trevor W Stone
Mar 30, 2010·The European Journal of Neuroscience·Alexandra L Ferguson, Trevor W Stone
Oct 31, 2002·Nature Reviews. Drug Discovery·Trevor W Stone, L Gail Darlington
Jan 18, 2012·The FEBS Journal·Gilles J Guillemin
Apr 25, 2003·British Journal of Pharmacology·Oscar P Dall'IgnaOscar P Dall'lgna
Aug 23, 2007·Metabolic Brain Disease·T W StoneL G Darlington
Jun 3, 2011·Fundamental & Clinical Pharmacology·Cristiani F BortolattoCristina W Nogueira

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