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Inhibition by the adenosine analogue, ( R ‐)‐N 6 ‐phenylisopropyl‐adenosine, of kainic acid neurotoxicity in rat hippocampus after systemic administration
Author(s) -
MacGregor D.G.,
Stone T.W.
Publication year - 1993
Publication title -
british journal of pharmacology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.432
H-Index - 211
eISSN - 1476-5381
pISSN - 0007-1188
DOI - 10.1111/j.1476-5381.1993.tb13572.x
Subject(s) - kainic acid , systemic administration , neurotoxicity , adenosine , chemistry , hippocampal formation , medicine , kynurenic acid , pharmacology , endocrinology , hippocampus , antagonist , biology , receptor , glutamate receptor , toxicity , microbiology and biotechnology , in vivo
1 Binding of the peripheral benzodiazepine receptor ligand, [ 3 H]‐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 [ 3 H]‐PK 11195 binding measured in rat hippocampal P 2 membranes 7 days later. Co‐treatment with the adenosine derivative R ‐phenylisopropyladenosine ( R ‐PIA) (100, 25 or 10 μg 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.