Potent effect of interleukin-1β to evoke ATP and adenosine release from rat hippocampal slices

In this study the effect of IL-1beta on [H-3]purine release from rat hippocampal slices was explored. IL-1beta (3 x 10(-18) -3 x 10(-14) M) concentration-dependently elevated the basal [3 H]purine efflux, and this effect was reversed by the selective IL-1RI receptor antagonist IL-1ra (10(-12) M). HPLC analysis revealed that the amount of [H-3]ATP and [H-3]adenosine significantly increased in the effluent in response to IL-1beta. The sodium channel inhibitor tetrodotoxin, the NMDA and non-NMDA receptor antagonists D(-)-2-amino-5-phosphonopentanoic acid (AP-5) plus 6-cyano-7-nitroquinoxaline-2,3-dione-disodium (CNQX) almost completely abolished IL-1beta-evoked [3 H]purine release. The effect of IL-1beta on [H-3]purine efflux was also prevented by the p38 MAP kinase inhibitor SB 203580, by the nucleoside transport inhibitor nitrobenzyl-thioinosine (NBTI) and by low temperature (4 degreesC). In summary IL-1beta triggers a transporter mediated [H-3]purine efflux in the hippocampus which is conveyed by glutamate receptor activation and the p38 MAP kinase pathway, and could serve as a mediator of IL-1beta-induced synaptic depression. (C) 2004 Published by Elsevier B.V.