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

摘要: 1. Quinolinic acid may be an important endogenous excitotoxin, but its concentrations in brain are low. We have therefore attempted to determine whether neurotoxicity can increased by the simultaneous presence of free radicals. 2. was injected into hippocampus anaesthetized rats at doses 40 and 80 nmols which produced little neuronal loss, 120 over 90% loss. 3. A mixture xanthine oxidase, a known source radical reactive oxygen species, also generated damage alone, killed 80% CA1 neurons when combined with quinolinic acid. Similarly, nitric oxide donor S-nitroso-N-acetylpenicillamine (SNAP) potentiated 4. The glutamate antagonist 5,7-dichlorokynurenic prevented acid, not that plus xanthine/xanthine indicating simply result enhancement NMDA receptor activation. 5. Three chemically dissimilar antagonists adenosine A(2A) receptors caused oxidase or SNAP. 6. It is concluded species potentiate site interaction probably distal receptor. Blockade protect against this damage, suggesting potential value prevention damage.