MODULATION BY ADENINE-NUCLEOTIDES OF EPILEPTIFORM ACTIVITY IN THE CA3REGION OF RAT HIPPOCAMPAL SLICES

1 Hippocampal slices (450 mu m) generate epileptiform bursts of an int erictal nature when perfused with a zero magnesium medium containing 4 -aminopyridine (50 mu M). The effect of adenine nucleotides on this ac tivity was investigated.2 ATP and adenosine depressed this epileptifor m activity in a concentration-dependent manner, with both purines bein g equipotent at concentrations above 10 mu M. 3 Adenosine deaminase 0. 2 u ml(-1), a concentration that annuls the effect of adenosine (50 mu M), did not significantly alter the depression of activity caused by ATP (50 mu M). 4 8-Cyclopentyl-1, 3-dimethylxanthine (CPT), an Al rece ptor antagonist, enhanced the discharge rate significantly and inhibit ed the depressant effect of both ATP and adenosine such that the net e ffect of ATP or adenosine plus CPT was excitatory. 5 Several ATP analo gues were also tested: alpha, beta-methyleneATP (alpha, beta-meATP), 2 -methylthioATP (2-meSATP) and uridine triphosphate (UTP). Only alpha, beta-meATP (10 mu M) produced an increase in the frequency of spontane ous activity which suggests a lack of involvement of P2Y or P2U recept ors. 6 Suramin and pyridoxalphosphate-6-azophenyl-2', 4'-disulphonic a cid (PPADS), P2 receptor antagonists, failed to inhibit the depression produced by ATP (50 mu M). The excitatory effect of alpha, beta-meATP (10 mu M) was inhibited by suramin (50 mu M) and PPADS (5 mu M). 7 AT P therefore depresses epileptiform activity in this model in a manner which is not consistent with the activation of known P1 or P2 receptor s, suggesting the involvement of a xanthine-sensitive nucleotide recep tor. The results are also indicative of an excitatory P2X receptor exi sting in the hippocampal CA3 region.