title: Probenecid, a gout remedy, inhibits pannexin 1 channels.
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.
authors.affiliation: Department of Physiology and Biophysics, University of Miami School of Medicine, Miami, Florida 33101, USA.
authors.forename: William
authors.initials: W
authors.lastname: Silverman
authors.forename: Silviu
authors.initials: S
authors.lastname: Locovei
authors.forename: Gerhard
authors.initials: G
authors.lastname: Dahl
mesh_terms: D000255:Adenosine Triphosphate / Q000378:metabolism*; D000818:Animals; D017630:Connexins / Q000037:antagonists & inhibitors / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D006074:Gout Suppressants / Q000494:pharmacology*; D007473:Ion Channels / Q000037:antagonists & inhibitors* / Q000235:genetics / Q000378:metabolism; D008564:Membrane Potentials; D009579:Nitrobenzoates / Q000494:pharmacology; D009865:Oocytes; D011339:Probenecid / Q000494:pharmacology*; D014982:Xenopus laevis; D000097002:Gap Junction beta-1 Protein
chemical_list: D000255:Adenosine Triphosphate; D017630:Connexins; D006074:Gout Suppressants; D007473:Ion Channels; D009579:Nitrobenzoates; D011339:Probenecid; D000097002:Gap Junction beta-1 Protein; C082917:GJA3 protein, human; C058176:5-nitro-2-(3-phenylpropylamino)benzoic acid