Probenecid directly impairs activation of the canine P2X7 receptor

Authors

Rachael Bartlett, University of WollongongFollow
Leanne Stokes, University of East AngliaFollow
Stephen J. Curtis, Albion Park Veterinary Hospital
Belinda L. Curtis, Albion Park Veterinary Hospital
Ronald Sluyter, University of WollongongFollow

RIS ID

118031

Publication Details

Bartlett, R., Stokes, L., Curtis, S. J., Curtis, B. L. & Sluyter, R. (2017). Probenecid directly impairs activation of the canine P2X7 receptor. Nucleosides, Nucleotides and Nucleic Acids: an international journal for rapid communication, 36 (12), 736-744.

Abstract

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 µM. Finally, ELISA measurements revealed that probenecid impairs ATP-induced interleukin-1β release in dog blood. In conclusion, this study reveals that probenecid can directly impair canine P2X7 activation.