The effect of nucleotides and adenosine on stimulus-evoked glutamate release from rat brain cortical slices

1 Evidence has previously been presented that P1 receptors for adenosine, a nd P2 receptors for nucleotides such as ATP, regulate stimulus-evoked relea se of biogenic amines from nerve terminals in the brain. Here we investigat ed whether adenosine and nucleotides exert presynaptic control over depolar isation-elicited glutamate release. 2 Slices of rat brain cortex were perfused and stimulated with pulses of 46 mM K+ in the presence of the glutamate uptake inhibitor L-trans-pyrrolidin e-2,3-dicarboxylic acid (0.2 mM). High K+ substantially increased efflux of glutamate from the slices. 3 Basal glutamate release was unchanged by the presence of nucleotides or a denosine at concentrations of 300 mu M. 4 Adenosine, ATP, ADP and adenosine 5'-O-(3-thiotriphoshate) at 300 mu M at tenuated depolarisation-evoked release of glutamate. However UTP,2-methylth io ATP, 2-methylthio ADP, and alpha,beta methylene ATP at 300 mu M had no e ffect on stimulated glutamate efflux. 5 Adenosine deaminase blocked the effect of adenosine. but left the respons e to ATP unchanged. 6 The Al antagonist 8-cyclopentyl-1,3-dipropylxanthine antagonised the inhi bitory effect of both adenosine and ATP. 7 Cibacron blue 3GA inhibited stimulus-evoked glutamate release when applie d alone. When cibacron blue 3GA was present with ATP, stimulus-evoked gluta mate release was almost eliminated. However, this P2 antagonist had no effe ct on the inhibition by adenosine. 8 These results show that the release of glutamate from depolarised nerve t erminals of the rat cerebral cortex is inhibited by adenosine and ATP. ATP appears to act directly and not through conversion to adenosine.