Mediation of the neuroprotective action of R-phenylisopropyl-adenosine through a centrally located adenosine A1 receptor.
1. Systemic injections of kainic acid, 10 mg kg-1, into adult rats resulted in lesions in the hippocampus, as assessed by peripheral benzodiazepine ligand binding. Co-administration of clonazepam at 1 mg kg-1 or 0.2 mg kg-1 prevented major seizures associated with kainate injections, but did not alter significantly the production of hippocampal damage. 2. The co-administration of the adenosine A1 agonist R-phenylisopropyladenosine (R-PIA, 25 micrograms kg-1, i.p.) abolished the lesions induced by kainic acid. 3. The presence of the selective A1 antagonist, 8-cyclopentyl-1,3-dipropylxanthine (250 or 50 micrograms kg-1, i.p.) abolished the R-PIA neuroprotective action. 4. The A1/A2 antagonist, 8-(p-sulphophenyl)theophylline (20 mg kg-1, i.p.) which cannot cross the blood brain barrier, did not alter significantly the neuroprotective action of R-PIA, indicating that the neuroprotective action of the purine may be predominantly central. 5. The time course of the neuroprotection was also examined. R-PIA was effective when administered 2 h before or after kainate administration. 6. The results emphasise the potential utility of systemically active adenosine A1 receptor ligands in reducing CNS gliosis induced by the activation of excitatory amino acid receptors.
MacGregor
D G
DG
Department of Pharmacology, University of Glasgow.
Miller
W J
WJ
Stone
T W
TW
D000818:Animals; D002998:Clonazepam / Q000494:pharmacology; D006624:Hippocampus / Q000166:cytology; D007546:Isoquinolines / Q000493:pharmacokinetics / Q000494:pharmacology; D007608:Kainic Acid / Q000037:antagonists & inhibitors / Q000633:toxicity; D008297:Male; D009474:Neurons / Q000187:drug effects*; D010660:Phenylisopropyladenosine / Q000494:pharmacology*; D058915:Purinergic P1 Receptor Antagonists; D051381:Rats; D017208:Rats, Wistar; D011963:Receptors, GABA-A / Q000187:drug effects; D018047:Receptors, Purinergic P1 / Q000378:metabolism; D013806:Theophylline / Q000031:analogs & derivatives / Q000494:pharmacology
D007546:Isoquinolines; D058915:Purinergic P1 Receptor Antagonists; D011963:Receptors, GABA-A; D018047:Receptors, Purinergic P1; D010660:Phenylisopropyladenosine; C053907:8-cyclopentyl-1,3-dimethylxanthine; D002998:Clonazepam; C031433:8-(4-sulfophenyl)theophylline; D013806:Theophylline; D007608:Kainic Acid; C037850:PK 11195