Kainate-evoked release of adenosine from the hippocampus of the anaesthetised rat: possible involvement of free radicals

J Neurochem. 1997 Jan;68(1):240-7. doi: 10.1046/j.1471-4159.1997.68010240.x.


Using microdialysis in the hippocampus of anaesthetised rats, the concentration of extracellular adenosine was estimated to be 0.8 microM. Kainic acid (0.1-25 mM) in the perfusate evoked a concentration-dependent release of adenosine with an EC50 of 940 microM. Two 5-min pulses of 1 mM kainic acid in the perfusate increased the dialysate levels with an S2/S1 ratio of 0.52 +/- 0.03. Kainate-evoked release of adenosine was reduced significantly by 10 microM tetrodotoxin and by a kappa-receptor agonist, U50, 488H (100 microM). The S2/S1 ratio was reduced by 4.5 microM 6-cyano-7-nitroquinoxaline-2,3-dione, a non-NMDA receptor antagonist, but not by the NMDA receptor blockers (+)-MK-801 (dizocilpine; 100 microM) or (+/-)-2-amino-5-phosphonopentanoic acid (1 mM), indicating a non-NMDA receptor-mediated process. The S2/S1 ratio was also reduced significantly by 10 mM ascorbic acid, 10 mM glutathione (a scavenger of hydroperoxides), and 1 mM oxypurinol (a xanthine oxidase inhibitor), indicating the possible involvement of free radicals. Neither the adenosine A1 receptor antagonist 8-cyclopentyl-1,3-dimethylxanthine (100 microM) nor the A1 adenosine receptor agonist R(-)-N6-(2-phenylisopropyl)adenosine (100 microM) affected release. Adenosine release evoked by kainic acid is therefore mediated by activation of non-NMDA receptors and may involve the propagation of action potentials and the production of free radicals.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adenosine / metabolism*
  • Adenosine / physiology
  • Animals
  • Free Radicals
  • Hippocampus / metabolism*
  • Hypoxanthine / metabolism
  • Inosine / metabolism
  • Kainic Acid / pharmacology*
  • Male
  • Microdialysis
  • Rats
  • Rats, Wistar
  • Receptors, Amino Acid / physiology
  • Time Factors
  • Xanthine
  • Xanthines / metabolism


  • Free Radicals
  • Receptors, Amino Acid
  • Xanthines
  • Xanthine
  • Hypoxanthine
  • Inosine
  • Adenosine
  • Kainic Acid