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MEMBRANE TRANSPORTERS, ION CHANNELS, AND PUMPS

Probenecid, a gout remedy, inhibits pannexin 1 channels

Department of Physiology and Biophysics, University of Miami School of Medicine, Miami, Florida

Submitted 25 April 2008 ; accepted in final form 29 June 2008

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.

connexin; transport; erythrocyte; ATP release