Probenecid interferes with renal oxidative metabolism: A potential pitfall in its use as an inhibitor of drug transport

摘要: The anionic drug probenecid has been traditionally used as an inhibitor of renal organic anion transport. More recently the was found to inhibit cation transport well, and it is retain intracellularly loaded fluorophores. In these investigations implicitly assumed that performs its activity through competition for Here we studied possibility provokes effect inhibition cellular oxidative metabolism. Oxygen consumption measured in isolated rat kidney cortex mitochondria. At concentrations 1 mM or higher, increased resting state (state 4) decreased ADP-stimulated respiration 3). A complete loss respiratory control observed at 10 mM probenecid. After incubating proximal tubular cells (PTC) 30 min with a concentration-dependent reduction ATP content observed, which significant higher. Using digital image fluorescence microscopy membrane potential PTC bisoxonol. mitochondrial effects were paralleled by depolarization plasma membrane, immediately after addition. All events are likely be result disordering due lipophilic character probenecid, may explain, least part, various inhibitory drug. We recommend cautious applying research. British Journal Pharmacology (2000) 131, 57–62; doi:10.1038/sj.bjp.0703541