Effects of suramin and reactive blue 2 (RB2), compounds known as antagonists at P2-purinoceptors, on ionic currents mediated through GABA and glutamate receptor channels were investigated in rat hippocampal neurons. Under whole-cell voltage-clamp, suramin (30 to 300 μM) and RB2 (10 to 100 μM) inhibited a current activated by 10 μM GABA in a concentration-dependent manner. Suramin (100 and 300 μM) and R132 (10 and 30 μM) also inhibited an inward current activated by kainic acid (100 μM), an agonist at non-NMDA type glutamate receptor channels, and an inward current activated by N-methyl-D-aspartate (NMDA; 100 μM), an agonist at NMDA type glutamate receptor channels. The inhibition by suramin or RB2 did not exhibit voltage-dependence between -30 and -90 mV in the case of the GABA- or the kainate-evoked current. In contrast, the inhibition by these compounds of the NMDA-evoked current exhibited voltage-dependence and was enhanced by hyperpolarization. When the concentration of agonists was increased by 5- or 10-fold, the magnitude of the inhibition by suramin of the kainate-evoked current and the magnitude of the inhibition by R132 of the NMDA-evoked current were attenuated. α,β-Methylene ATP (100 μM) did not affect the GABA-, kainate- or NMDA-activated current. The results suggest that suramin and RB 2 inhibit GABA receptor channels and glutamate receptor channels. The blockade of these channels must be taken into account when these compounds are used as pharmacological tools to examine an involvement of P2-purinoceptors, especially in preparations where GABAergic or glutamatergic neurotransmission is expected.
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