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

Abstract

In this study the effect of IL-1β on [ 3H]purine release from rat hippocampal slices was explored. IL-1β (3×10 −18–3×10 −14 M) concentration-dependently elevated the basal [ 3H]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 [ 3H]ATP and [ 3H]adenosine significantly increased in the effluent in response to IL-1β. 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-1β-evoked [ 3H]purine release. The effect of IL-1β on [ 3H]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 °C). In summary IL-1β triggers a transporter mediated [ 3H]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-1β-induced synaptic depression.