Potent effect of interleukin-1 beta to evoke ATP and adenosine release from rat hippocampal slices.
In this study the effect of IL-1 beta on [(3)H]purine release from rat hippocampal slices was explored. IL-1 beta (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 [(3)H]ATP and [(3)H]adenosine significantly increased in the effluent in response to IL-1 beta. 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-1 beta-evoked [(3)H]purine release. The effect of IL-1 beta on [(3)H]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 degrees C). In summary IL-1 beta triggers a transporter mediated [(3)H]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-1 beta-induced synaptic depression.
Sperlágh
Beáta
B
Laboratory of Molecular Pharmacology, Institute of Experimental Medicine, Hungarian Academy of Sciences, H-1083 Budapest, Szigony u. 43, Hungary. sperlagh@koki.hu
Baranyi
Mária
M
Haskó
György
G
Vizi
E Sylvester
ES
D000241:Adenosine / Q000378:metabolism*; D000255:Adenosine Triphosphate / Q000378:metabolism*; D000818:Animals; D002851:Chromatography, High Pressure Liquid; D004305:Dose-Response Relationship, Drug; D004791:Enzyme Inhibitors / Q000494:pharmacology; D018691:Excitatory Amino Acid Antagonists / Q000494:pharmacology; D045604:Extracellular Fluid / Q000737:chemistry; D006624:Hippocampus / Q000187:drug effects* / Q000378:metabolism; D053590:Interleukin 1 Receptor Antagonist Protein; D007375:Interleukin-1 / Q000494:pharmacology*; D017774:Long-Term Potentiation / Q000187:drug effects / Q000502:physiology; D020928:Mitogen-Activated Protein Kinases / Q000187:drug effects / Q000378:metabolism; D009924:Organ Culture Techniques; D051381:Rats; D017470:Receptors, Glutamate / Q000187:drug effects / Q000378:metabolism; D012795:Sialoglycoproteins / Q000494:pharmacology; D009435:Synaptic Transmission / Q000187:drug effects / Q000502:physiology; D048051:p38 Mitogen-Activated Protein Kinases
D004791:Enzyme Inhibitors; D018691:Excitatory Amino Acid Antagonists; D053590:Interleukin 1 Receptor Antagonist Protein; D007375:Interleukin-1; D017470:Receptors, Glutamate; D012795:Sialoglycoproteins; D000255:Adenosine Triphosphate; D020928:Mitogen-Activated Protein Kinases; D048051:p38 Mitogen-Activated Protein Kinases; D000241:Adenosine