Kainate-evoked release of adenosine from the hippocampus of the anaesthetised rat: possible involvement of free radicals.
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.
Carswell
H V
HV
Division of Neuroscience and Biomedical Systems, University of Glasgow, Scotland.
Graham
D I
DI
Stone
T W
TW
D000241:Adenosine / Q000378:metabolism* / Q000502:physiology; D000818:Animals; D005609:Free Radicals; D006624:Hippocampus / Q000378:metabolism*; D019271:Hypoxanthine / Q000378:metabolism; D007288:Inosine / Q000378:metabolism; D007608:Kainic Acid / Q000494:pharmacology*; D008297:Male; D017551:Microdialysis; D051381:Rats; D017208:Rats, Wistar; D017459:Receptors, Amino Acid / Q000502:physiology; D013997:Time Factors; D019820:Xanthine; D014970:Xanthines / Q000378:metabolism
D005609:Free Radicals; D017459:Receptors, Amino Acid; D014970:Xanthines; D019820:Xanthine; D019271:Hypoxanthine; D007288:Inosine; D000241:Adenosine; D007608:Kainic Acid