PT - JOURNAL ARTICLE AU - William R. Haines AU - Gonzalo E. Torres AU - Mark M. Voigt AU - Terrance M. Egan TI - Properties of the Novel ATP-Gated Ionotropic Receptor Composed of the P2X<sub>1</sub> and P2X<sub>5</sub> Isoforms DP - 1999 Oct 01 TA - Molecular Pharmacology PG - 720--727 VI - 56 IP - 4 4099 - http://molpharm.aspetjournals.org/content/56/4/720.short 4100 - http://molpharm.aspetjournals.org/content/56/4/720.full SO - Mol Pharmacol1999 Oct 01; 56 AB - 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 P2X1/5 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 &gt; adenosine 5′-O-(3-thiotriphosphate) &gt; α,β-methylene ATP &gt; ADP &gt; 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 P2X1/5 receptors; however, the P2X1/5 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 P2X1/5 receptor channel and provide a basis to further evaluate ATP-induced currents in native tissues. The American Society for Pharmacology and Experimental Therapeutics