Figure 1.
The ATP analogs β,γ-ImATP and α,β-MeATP biphasically modulate the evoked release of glutamate from rat hippocampal nerve terminals through activation of P2 receptors. A, Time course of tritium release from rat hippocampal synaptosomes challenged with two periods of stimulation with 20 mm K+ for 30 s (S1 and S2), as indicated by the bars above the abscissa. This representative experiment shows that 60 μm β,γ-ImATP (filled symbols), applied through the superfusate in the test chambers 2 min before S2 (as indicated by the top bar), increases glutamate release in S2. B, The nonselective P2X/P2Y receptors agonist β,γ-ImATP caused a concentration-dependent biphasic effect on the evoked release of glutamate, inhibiting at the lower (10-30 μm) and facilitating at higher (60-100 μm) concentrations, whereas the P2X-prefering agonist α,β-MeATP only facilitated the evoked release of glutamate at all concentrations tested. *p < 0.05 compared with 0%. C, The facilitatory effects of both 60 μm β,γ-ImATP and 60 μm α,β-MeATP were not modified in the presence of 50 nm ZM241385 (a selective antagonist of adenosine A2A receptors) but were prevented by 20 μm PPADS (nonselective P2 receptor antagonist). D, The inhibitory effect of 30 μm β,γ-ImATP was not modified in the presence of 50 nm DPCPX (selective antagonist of adenosine A1 receptor) but were prevented by both 75 μm suramin and 20 μm PPADS. *p < 0.05 compared with the effects of ATP analogs. The results are mean ± SEM of four to six experiments.