Inhibition by the adenosine analogue, (R-)-N6-phenylisopropyladenosine, of kainic acid neurotoxicity in rat hippocampus after systemic administration.
1. Binding of the peripheral benzodiazepine receptor ligand, [3H]-PK 11195, to rat hippocampal membranes has been used to quantify the reactive gliosis resulting from neuronal death induced by intraperitoneally administered kainic acid. 2. Intraperitoneal administration of kainic acid (10 mg kg-1) caused a 350-500% increase in [3H]-PK 11195 binding measured in rat hippocampal P2 membranes 7 days later. Co-treatment with the adenosine derivative R-phenylisopropyladenosine (R-PIA) (100, 25 or 10 micrograms kg-1, i.p.) abolished this elevation. The protective action of R-PIA could itself be abolished by co-treatment with 8-phenyltheophylline (1 mg kg-1). 3. Body temperatures were recorded in the antagonist experiments and no significant changes were recorded, suggesting that the protective action of R-PIA was not mediated by hypothermia. 4. Since systemic kainic acid-induced neurotoxicity has been claimed as a good model of neuronal death in temporal lobe epilepsy, the results suggest that the systemic administration of purines in low doses may provide protection against certain neurodegenerative insults.
MacGregor
D G
DG
Department of Pharmacology, University of Glasgow.
Stone
T W
TW
D000818:Animals; D001522:Behavior, Animal / Q000187:drug effects; D001831:Body Temperature / Q000187:drug effects; D006624:Hippocampus / Q000473:pathology*; D007546:Isoquinolines / Q000378:metabolism / Q000493:pharmacokinetics / Q000494:pharmacology; D007608:Kainic Acid / Q000037:antagonists & inhibitors* / Q000633:toxicity; D007700:Kinetics; D008297:Male; D009422:Nervous System Diseases / Q000139:chemically induced* / Q000473:pathology; D010660:Phenylisopropyladenosine / Q000494:pharmacology*; D051381:Rats; D017208:Rats, Wistar; D013806:Theophylline / Q000031:analogs & derivatives / Q000494:pharmacology
D007546:Isoquinolines; D010660:Phenylisopropyladenosine; D013806:Theophylline; C028322:8-phenyltheophylline; D007608:Kainic Acid; C037850:PK 11195