The effects of adenine dinucleotides on epileptiform activity in the CA3 region of rat hippocampal slices.
Alpha, omega-adenine dinucleotides (Ap(n)A) consist of two adenosine molecules linked at the 5' position by phosphate groups, the number of which is denoted by n and can range from 2 to 6. The aim of this study was to investigate the effect of Ap4A and Ap5A on the rate of epileptiform activity. Hippocampal slices (450 microm), when perfused with a medium containing no added magnesium and 4-aminopyridine (50 microM), generate epileptiform activity of an interictal nature. Ap4A and Ap5A at 1 microM depressed the discharge rate to a significant extent. At this concentration adenosine (1 microM) did not produce any effect. However at 10 microM adenosine, Ap4A and Ap5A all decreased the burst frequency. Adenosine deaminase (0.2 U/ml) totally annulled the inhibition of epileptiform activity produced by 10 microM adenosine or 1 microM Ap4A and Ap5A. Adenosine deaminase did not significantly change the maximum depression of activity produced by 10 microM Ap4A and Ap5A. 8-cyclopentyl-1,3-dimethylxanthine, an A1, receptor antagonist, increased the basal rate of epileptiform activity and prevented the depression of burst discharges by Ap4A. 5'-adenylic acid deaminase converts AMP into IMP which is inactive. 5'-adenylic acid deaminase did not prevent the inhibitory effects of Ap4A. The results suggests that in the CA3 region of the hippocampus, Ap4A and Ap5A act partly by stimulating xanthine-sensitive receptors directly and partly through the formation of the metabolite, adenosine.
Ross
F M
FM
Institute of Biomedical and Life Sciences, Division of Neuroscience and Biomedical Systems, University of Glasgow, UK.
Brodie
M J
MJ
Stone
T W
TW
D000659:AMP Deaminase / Q000494:pharmacology*; D000243:Adenosine Deaminase / Q000494:pharmacology*; D000818:Animals; D004594:Electrophysiology; D004827:Epilepsy / Q000503:physiopathology*; D006624:Hippocampus / Q000187:drug effects* / Q000503:physiopathology*; D066298:In Vitro Techniques; D008297:Male; D051381:Rats; D017208:Rats, Wistar; D014970:Xanthines / Q000494:pharmacology*
C112774:1,3-dimethyl-8-cyclopentylxanthine; D014970:Xanthines; D000243:Adenosine Deaminase; D000659:AMP Deaminase