Sustained depolarisation induces changes in the extracellular concentrations of purine and pyrimidine nucleosides in the rat thalamus

ATP and adenosine are well-known neuroactive compounds. Other nucleotides a nd nucleosides may also be involved in different brain functions. This pape r reports on extracellular concentrations of nucleobases and nucleosides (u racil, hypoxanthine, xanthine, uridine, 2'-deoxycytidine, 2'-deoxyuridine, inosine, guanosine, thymidine, adenosine) in response to sustained depolari sation, using in vivo brain microdialysis technique in the rat thalamus. Hi gh-potassium solution, the glutamate agonist kainate, and the Na+/K+ ATPase blocker ouabain were applied in the perfusate of microdialysis probes and induced release of various purine and pyrimidine nucleosides. All three typ es of depolarisation increased the level of hypoxanthine, uridine, inosine, guanosine and adenosine. The levels of measured deoxynucleosides (2'-deoxy cytidine, 2'-deoxyuridine and thymidine) decreased or did not change, depen ding on the type of depolarisation. Kainate-induced changes were TTX insens itive, and ouabain-induced changes for inosine, guanosine, 2'-deoxycytidine and 2'-deoxyuridine were TTX sensitive. In contrast, TTX application witho ut depolarisation decreased the extracellular concentrations of hypoxanthin e, uridine, inosine, guanosine and adenosine. Our data suggest that various nucleosides may be released from cells expose d to excessive activity and, thus, support several different lines of resea rch concerning the regulatory roles of nucleosides. (C) 2000 Elsevier Scien ce Ltd. All rights reserved.