Probenecid, a gout remedy, inhibits pannexin 1 channels
- 1 September 2008
- journal article
- research article
- Published by American Physiological Society in American Journal of Physiology-Cell Physiology
- Vol. 295 (3), C761-C767
- https://doi.org/10.1152/ajpcell.00227.2008
Abstract
Probenecid is a well-established drug for the treatment of gout and is thought to act on an organic anion transporter, thereby affecting uric acid excretion in the kidney by blocking urate reuptake. Probenecid also has been shown to affect ATP release, leading to the suggestion that ATP release involves an organic anion transporter. Other pharmacological evidence and the observation of dye uptake, however, suggest that the nonvesicular release of ATP is mediated by large membrane channels, with pannexin 1 being a prominent candidate. In the present study we show that probenecid inhibited currents mediated by pannexin 1 channels in the same concentration range as observed for inhibition of transport processes. Probenecid did not affect channels formed by connexins. Thus probenecid allows for discrimination between channels formed by connexins and pannexins.Keywords
This publication has 57 references indexed in Scilit:
- Innexins form two types of channelsFEBS Letters, 2007
- Pannexin1 is part of the pore forming unit of the P2X7 receptor death complexFEBS Letters, 2007
- Pannexin-1 mediates large pore formation and interleukin-1β release by the ATP-gated P2X7 receptorThe EMBO Journal, 2006
- Pannexin1 is expressed by neurons and glia but does not form functional gap junctionsGlia, 2006
- Glutamate acts at NMDA receptors on fresh bovine and on cultured human retinal pigment epithelial cells to trigger release of ATPThe Journal of Physiology, 2006
- Pannexin 1 in erythrocytes: Function without a gapProceedings of the National Academy of Sciences of the United States of America, 2006
- Brefeldin A Block of Integrin-dependent Mechanosensitive ATP Release from Xenopus Oocytes Reveals a Novel Mechanism of MechanotransductionOnline Journal of Public Health Informatics, 2001
- Effect of probenecid, verapamil and progesterone on the concentration-dependent and temperature-sensitive human erythrocyte uptake and export of guanosine 3′,5′ cyclic monophosphate (cGMP)Scandinavian Journal of Clinical and Laboratory Investigation, 1995
- Clinical Pharmacokinetics of ProbenecidClinical Pharmacokinetics, 1981
- pH gradient-stimulated transport of urate and p-aminohippurate in dog renal microvillus membrane vesicles.JCI Insight, 1980