PT - JOURNAL ARTICLE AU - Caterina Virginio AU - Graeme Robertson AU - Annmarie Surprenant AU - R. Alan North TI - Trinitrophenyl-Substituted Nucleotides Are Potent Antagonists Selective for P2X<sub>1</sub>, P2X<sub>3</sub>, and Heteromeric P2X<sub>2/3</sub> Receptors DP - 1998 Jun 01 TA - Molecular Pharmacology PG - 969--973 VI - 53 IP - 6 4099 - http://molpharm.aspetjournals.org/content/53/6/969.short 4100 - http://molpharm.aspetjournals.org/content/53/6/969.full SO - Mol Pharmacol1998 Jun 01; 53 AB - There are currently seven P2X receptor subunits (P2X1–7) defined by molecular cloning. The functional identification of these receptors has relied primarily on the potency of α,β-methylene-ATP relative to that of ATP and on the kinetics of receptor desensitization. In the present experiments we found that the 2′,3′-O-(2,4,6-trinitrophenyl)-substituted analogs of ATP are selective and potent antagonists at some but not all P2X receptors. The trinitrophenyl analogs of ATP, ADP, AMP, and GTP produced a reversible inhibition of ATP-evoked currents in human embryonic kidney 293 cells expressing P2X1 receptors, P2X3 receptors, or both P2X2 and P2X3 (heteromeric) receptors; IC50 values were close to 1 nm. These compounds were at least 1000-fold less effective in blocking currents in cells expressing P2X2, P2X4, or P2X7receptors (P2X5 and P2X6 not tested). GTP, 2,4,6-trinitrophenol, and the 2′,3′-trinitrophenyl analog of adenosine (0.1–10 μm) had no effect. Thus, we have identified a structural motif that confers antagonist action at P2X receptors that contain P2X1 or P2X3 subunits (the α,β-methylene-ATP-sensitive subclass). The American Society for Pharmacology and Experimental Therapeutics