RELEASE OF ATP FROM CULTURED RAT ASTROCYTES ELICITED BY GLUTAMATE-RECEPTOR ACTIVATION

The release of ATP was studied in cultures of astrocytes derived from the brain hemispheres of newborn rats. There was a basal efflux of ATP , which was increased up to 19-fold by glutamate (300-1000 mu M), N-me thyl-D-aspartate (20-500 mu M), pha-amino-3-hydroxy-5-methylisoxazole- 4-propionate (AMPA; 30-100 mu M) and kainate (20 mu M). The N-methyl-D -aspartate receptor-selective antagonist 2-amino-5-phosphonopentanoate (100 mu M) blocked the effect of N-methyl-D-aspartate but not the eff ects of AMPA, kainate and glutamate. The AMPA receptor-selective antag onist -dihydroxp-6-nitro-7-sulfamoyl-benzo(f)quinoxaline (30 mu M) blo cked the effect of AMPA and also of glutamate and N-methyl-D-aspartate , but not the effect of kainate. The kainate receptor-selective antago nist D-glutamyl-amino-methanesulfonate (30 mu M) blocked the effect of kainate but not of glutamate. Glutamate (1000 mu M) did not increase the release of lactate dehydrogenase from astrocytes. Excitatory amino acids are known to release adenyl compounds in the brain. The present results identify one adenyl compound thus released, namely ATP, and i dentify astrocytes as one source. The release is brought about by acti vation of any of the three ionotropic glutamate receptor types--N-meth yl-D-aspartate, AMPA and kainate receptors. AMPA receptors seem to med iate at least a part of the effect of glutamate itself, but the involv ement of other receptors cannot be ruled out. ATP and its degradation products, such as adenosine, once released, may exert acute as well as trophic effects on neurons and glial cells. (C) 1997 IBRO. Published by Elsevier Science Ltd.