Properties of the novel ATP-gated ionotropic receptor composed of the P2X(1) and P2X(5) isoforms.
We recently reported that a novel hetero-oligomeric P2X receptor is formed from the P2X(1) and P2X(5) isoforms when coexpressed in human embryonic kidney 293 cells (). 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. EC(50) 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) > alpha,beta-methylene ATP > ADP > CTP. alpha,beta-methylene ADP, UTP, GTP, and AMP were ineffective. Only ATP and 2 methylthio ATP were full agonists. IC(50) 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 P2X(1) and P2X(1/5) receptors; however, the P2X(1/5) receptor was much less sensitive to TNP-ATP than was the P2X(1) receptor. The amplitude of peak ATP-gated current was relatively insensitive to changes in [Ca(2+)](O) (1-30 mM). Finally, plateau currents were potentiated by low concentrations of pyridoxal phosphate-6-azophenyl-2', 4'-disulfonic acid and by raising [Ca(2+)](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.
Haines
W R
WR
Department of Pharmacological and Physiological Sciences, St. Louis University School of Medicine, St. Louis, Missouri 63104, USA. haineswr@slu.edu
Torres
G E
GE
Voigt
M M
MM
Egan
T M
TM
D000255:Adenosine Triphosphate / Q000502:physiology; D000818:Animals; D019556:COS Cells; D002118:Calcium / Q000494:pharmacology; D002478:Cells, Cultured; D006224:Cricetinae; D003412:Cricetulus; D004594:Electrophysiology; D006801:Humans; D020033:Protein Isoforms / Q000819:agonists / Q000037:antagonists & inhibitors / Q000502:physiology*; D058910:Purinergic P2 Receptor Agonists; D058919:Purinergic P2 Receptor Antagonists; D018048:Receptors, Purinergic P2 / Q000502:physiology*; D058469:Receptors, Purinergic P2X; D058485:Receptors, Purinergic P2X5
C546465:P2RX5 protein, human; D020033:Protein Isoforms; D058910:Purinergic P2 Receptor Agonists; D058919:Purinergic P2 Receptor Antagonists; D018048:Receptors, Purinergic P2; D058469:Receptors, Purinergic P2X; D058485:Receptors, Purinergic P2X5; D000255:Adenosine Triphosphate; D002118:Calcium