The effects of adenine dinucleotides on epileptiform activity in the CA3 region of rat hippocampal slices

Abstract

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 Ap 4A and Ap 5A on the rate of epileptiform activity. Hippocampal slices (450 μm), when perfused with a medium containing no added magnesium and 4-aminopyridine (50 μM), generate epileptiform activity of an interictal nature. Ap 4A and Ap 5A at 1 μM depressed the discharge rate to a significant extent. At this concentration adenosine (1 μM) did not produce any effect. However at 10 μM adenosine, Ap 4A and Ap 5A all decreased the burst frequency. Adenosine deaminase (0.2 U/ml) totally annulled the inhibition of epileptiform activity produced by 10 μM adenosine or 1 μM Ap 4A and Ap 5A. Adenosine deaminase did not significantly change the maximum depression of activity produced by 10 μM Ap 4A and Ap 5A. 8-cyclopentyl-1,3-dimethylxanthine, an A 1, receptor antagonist, increased the basal rate of epileptiform activity and prevented the depression of burst discharges by Ap 4A. 5′-adenylic acid deaminase converts AMP into IMP which is inactive. 5′-adenylic acid deaminase did not prevent the inhibitory effects of Ap 4A. The results suggests that in the CA3 region of the hippocampus, Ap 4A and Ap 5A act partly by stimulating xanthine-sensitive receptors directly and partly through the formation of the metabolite, adenosine.