Effect of P2-purinoceptor antagonists on glutamatergic transmission in the rat hippocampus.

1. A study has been made of the effects of P2-purinoceptor antagonists on the evoked excitatory postsynaptic currents (e.p.s.cs) generated in CA1 pyramidal cells on stimulation of Schaffer collaterals and in CA3 pyramidal cells on stimulation of mossy fibres. The effects of these antagonists on currents generated in the cells on application of glutamate has also been determined. 2. Suramin blocked the evoked e.p.s.cs with an 50% inhibition (ID50) of 62 +/- 8 microM (mean +/- s.e.mean, n = 17), spontaneous miniature e.p.s.cs and the currents induced by application of 100 microM glutamate with an ID50 = 121 +/- 36 microM (n = 15) in all the cells studied. 3. Reactive Blue 2 (RB-2) in a concentration of 200 microM decreased the e.p.s.cs by 80 +/- 10% (n = 6) and the glutamate-activated currents by 83 +/- 3% (n = 6). 4. Pyridoxal-phosphate-6-azophenyl-2',4'-disulphonic acid (PPADS) in the concentration-range of 40-500 microM decreased the amplitude of the e.p.s.cs in 12 out of 13 cells studied. PPADS at 200 microM reduced the amplitude of the e.p.s.cs by 60 +/- 10% (n = 3). PPADS did not affect the glutamate-induced currents in 4 cells and produced potentiation of the current amplitude by 60 +/- 10% in 4 other cells. 5. These results suggest that both presynaptic and postsynaptic P2-purinoceptors in the hippocampus can modulate the release and action of endogenous glutamate.