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 m olecules 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(4)A and Ap(5)A on the rate of epi leptiform activity. Hippocampal slices (450 mu m), when perfused with a medium containing no added magnesium and 4-aminopyridine (50 mu M), generate epileptiform activity of an interictal nature. Ap(4)A and Ap( 5)A at 1 mu M depressed the discharge rate to a significant extent. At this concentration adenosine (1 mu M) did not produce any effect. How ever at 10 mu M adenosine, Ap(4)A and Ap(5)A all decreased the burst f requency. Adenosine deaminase (0.2 U/ml) totally annulled the inhibiti on of epileptiform activity produced by 10 mu M adenosine or 1 mu M Ap (4)A and Ap(5)A. Adenosine deaminase did not significantly change the maximum depression of activity produced by 10 mu M Ap(4)A and Ap(5)A. 8-cyclopentyl-1,3-dimethylxanthine, an A(1), receptor antagonist, incr eased the basal rate of epileptiform activity and prevented the depres sion of burst discharges by Ap(4)A. 5'-adenylic acid deaminase convert s AMP into IMP which is inactive. 5'-adenylic acid deaminase did not p revent the inhibitory effects of Ap(4)A. The results suggests that in the CA3 region of the hippocampus, Ap(4)A and Ap(5)A act partly by sti mulating xanthine-sensitive receptors directly and partly through the formation of the metabolite, adenosine. (C) 1998 IBRO. Published by El sevier Science Ltd.