Probenecid directly impairs activation of the canine P2X7 receptor |
| |
| Authors: | Rachael Bartlett Leanne Stokes Stephen J. Curtis Belinda L. Curtis |
| |
| Affiliation: | 1. School of Biological Sciences, University of Wollongong, Wollongong, NSW, Australia;2. Centre for Medical and Molecular Bioscience, University of Wollongong, Wollongong, NSW, Australia;3. Illawarra Health and Medical Research Institute, Wollongong, NSW, Australia;4. School of Pharmacy, University of East Anglia, Norwich, United Kingdom;5. Albion Park Veterinary Hospital, Albion Park, NSW, Australia |
| |
| 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. |
| |
| Keywords: | Purinergic receptor extracellular nucleotide probenecid gout monocyte cytokine dog |
|
|
