Abstract

We recently reported that a novel hetero-oligomeric P2X receptor is formed from the P2X₁ and P2X₅ isoforms when coexpressed in human embryonic kidney 293 cells (Torres et al., 1998). A more complete description of the pharmacology of this novel receptor is presented here. A brief application of ATP to a voltage-clamped cell transiently expressing P2X_1/5 receptors resulted in a biphasic current that rapidly reached a peak and then decayed to a sustained plateau. Washout of ATP was accompanied by generation and fade of a pronounced tail of inward current. EC₅₀ values were determined from concentration-response curves for a range of agonists. The rank order of agonist potency was ATP ≥ 2 methylthio ATP > adenosine 5′-O-(3-thiotriphosphate) > α,β-methylene ATP > ADP > CTP. α,β-methylene ADP, UTP, GTP, and AMP were ineffective. Only ATP and 2 methylthio ATP were full agonists. IC₅₀ values were determined from concentration-response curves for three commonly used purinergic antagonists. Suramin and pyridoxal phosphate-6-azophenyl-2′, 4′-disulfonic acid were equipotent at P2X₁ and P2X_1/5 receptors; however, the P2X_1/5 receptor was much less sensitive to TNP-ATP than was the P2X₁ receptor. The amplitude of peak ATP-gated current was relatively insensitive to changes in [Ca²⁺]_O (1–30 mM). Finally, plateau currents were potentiated by low concentrations of pyridoxal phosphate-6-azophenyl-2′, 4′-disulfonic acid and by raising [Ca²⁺]_O. These results provide additional information on the pharmacological profile of the recombinant P2X_1/5 receptor channel and provide a basis to further evaluate ATP-induced currents in native tissues.