Quinolinic acid neurotoxicity: protection by intracerebral phenylisopropyladenosine (PIA) and potentiation by hypotension.
In the present study we have used the purine agonist R-phenylisopropyladenosine (PIA) which suppresses excitatory amino acid release to assess its effect on quinolinate toxicity. Quinolinic acid was injected into the rat hippocampus alone or with PIA and the animals allowed to recover. After 4 days the brain was removed for histological examination. The extent of neuronal degeneration was assessed blind by an independent observer on a scale of 0 (no damage) to 10 (complete degeneration). Co-administration of PIA protected against the toxicity, and this protective action of PIA was blocked by a xanthine adenosine receptor antagonist. However, systemic injections of PIA or the non-purine ganglion blocking drug trimetaphan, both of which caused significant depression of blood pressure, potentiated quinolinate toxicity. The results may indicate an interaction between endogenous excitotoxins and episodes of hypotension which may be critical in determining cell death in the CNS.
Department of Pharmacology, University of Glasgow, U.K.
J H
JH
Connick
T W
TW
Stone
D000241:Adenosine / Q000031:analogs & derivatives*; D000818:Animals; D001794:Blood Pressure; D006624:Hippocampus / Q000166:cytology / Q000187:drug effects* / Q000503:physiopathology; D007022:Hypotension / Q000503:physiopathology*; D008297:Male; D009410:Nerve Degeneration / Q000187:drug effects*; D010660:Phenylisopropyladenosine / Q000037:antagonists & inhibitors / Q000494:pharmacology*; D011725:Pyridines / Q000633:toxicity*; D011805:Quinolinic Acids / Q000633:toxicity*; D051381:Rats; D011919:Rats, Inbred Strains; D014294:Trimethaphan / Q000494:pharmacology
D011725:Pyridines; D011805:Quinolinic Acids; D010660:Phenylisopropyladenosine; D014294:Trimethaphan; D000241:Adenosine