Probenecid directly impairs activation of the canine P2X7 receptor.

The current study aimed to determine if probenecid could directly impair the canine P2X7 receptor, a ligand-gated cation channel activated by extracellular adenosine 5'-triphosphate (ATP). Patch clamp measurements demonstrated that probenecid impairs ATP-induced inward currents in HEK-293 cells expressing canine P2X7. Flow cytometric measurements of ethidium(+) uptake into HEK-293 cells expressing canine P2X7 showed that probenecid impairs ATP-induced pore formation in a concentration-dependent manner, with a half maximal inhibitory concentration of 158 mu M. Finally, ELISA measurements revealed that probenecid impairs ATP-induced interleukin-1 beta release in dog blood. In conclusion, this study reveals that probenecid can directly impair canine P2X7 activation.