Renal transport of gossypol in the rabbit.
The present work was carried out to investigate the transport characteristics of gossypol, a toxic weak organic acid (pK = 7.2) contained in cottonseed, into the rabbit renal cortical slice. The uptake of gossypol increased linearly during a 2-hr incubation after which it leveled off with the average slice-to-medium concentration ratio (S/M) slightly above 20. In the presence of metabolic inhibitors, the S/M gossypol leveled off at about 9, suggesting an extensive binding of gossypol to tissue proteins. The uptake of gossypol was significantly inhibited by p-aminohippurate (PAH), probenecid, ouabain, and DIDS, all of which are known inhibitors of renal organic anion transport. However, the gossypol uptake was not affected by tetraethylammonium (TEA), a prototypical organic cation. Kinetic studies indicated that the apparent Km for gossypol transport is 0.28 mM, and also that probenecid inhibits gossypol transport in a competitive manner. It is concluded that gossypol is transported by the renal tubule through the classic organic anion system.
D019297:2,4-Dinitrophenol; D017878:4,4'-Diisothiocyanostilbene-2,2'-Disulfonic Acid; D012856:4-Acetamido-4'-isothiocyanatostilbene-2,2'-disulfonic Acid / Q000031:analogs & derivatives / Q000494:pharmacology; D000818:Animals; D001667:Binding, Competitive; D001692:Biological Transport / Q000187:drug effects; D001693:Biological Transport, Active / Q000187:drug effects; D004140:Dinitrophenols / Q000494:pharmacology; D006072:Gossypol / Q000378:metabolism*; D066298:In Vitro Techniques; D007460:Iodoacetamide / Q000494:pharmacology; D007672:Kidney Cortex / Q000378:metabolism*; D007700:Kinetics; D009584:Nitrogen / Q000494:pharmacology; D010042:Ouabain / Q000494:pharmacology; D011339:Probenecid / Q000494:pharmacology; D011817:Rabbits; D019789:Tetraethylammonium; D013757:Tetraethylammonium Compounds / Q000494:pharmacology; D010130:p-Aminohippuric Acid / Q000494:pharmacology
D004140:Dinitrophenols; D013757:Tetraethylammonium Compounds; D012856:4-Acetamido-4'-isothiocyanatostilbene-2,2'-disulfonic Acid; D010042:Ouabain; D019789:Tetraethylammonium; D006072:Gossypol; D009584:Nitrogen; D011339:Probenecid; D019297:2,4-Dinitrophenol; D017878:4,4'-Diisothiocyanostilbene-2,2'-Disulfonic Acid; D010130:p-Aminohippuric Acid; D007460:Iodoacetamide