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

J Neuroimmunol. 2004 Jun;151(1-2):33-9. doi: 10.1016/j.jneuroim.2004.02.004.

Abstract

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.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Adenosine / metabolism*
  • Adenosine Triphosphate / metabolism*
  • Animals
  • Chromatography, High Pressure Liquid
  • Dose-Response Relationship, Drug
  • Enzyme Inhibitors / pharmacology
  • Excitatory Amino Acid Antagonists / pharmacology
  • Extracellular Fluid / chemistry
  • Hippocampus / drug effects*
  • Hippocampus / metabolism
  • Interleukin 1 Receptor Antagonist Protein
  • Interleukin-1 / pharmacology*
  • Long-Term Potentiation / drug effects
  • Long-Term Potentiation / physiology
  • Mitogen-Activated Protein Kinases / drug effects
  • Mitogen-Activated Protein Kinases / metabolism
  • Organ Culture Techniques
  • Rats
  • Receptors, Glutamate / drug effects
  • Receptors, Glutamate / metabolism
  • Sialoglycoproteins / pharmacology
  • Synaptic Transmission / drug effects
  • Synaptic Transmission / physiology
  • p38 Mitogen-Activated Protein Kinases

Substances

  • Enzyme Inhibitors
  • Excitatory Amino Acid Antagonists
  • Interleukin 1 Receptor Antagonist Protein
  • Interleukin-1
  • Receptors, Glutamate
  • Sialoglycoproteins
  • Adenosine Triphosphate
  • Mitogen-Activated Protein Kinases
  • p38 Mitogen-Activated Protein Kinases
  • Adenosine