Effects of gossypol on PAH transport in the rabbit kidney slice.
The present work was carried out to investigate if gossypol, a toxic weak organic acid (pK = 7.2) contained in cottonseed, is secreted by the renal proximal tubule through the organic anion transport system in the rabbit. The slice uptake of p-aminohippurate (PAH), a prototypical organic anion, was significantly inhibited (by 30%) only when the medium concentration of gossypol was raised to 10(-4) M. However, gossypol at the latter concentration also induced a 30% inhibition of the slice uptake of tetraethylammonium (TEA), a prototypical organic cation. Moreover, gossypol at 10(-4) M significantly decreased the slice oxygen consumption (congruent to 30%) and Mg-ATPase (70%) and Na-K-ATPase (90%) activities of renal cortical microsomes, while it significantly decreased the intracellular (K+). These results indicate that gossypol inhibits PAH uptake through nonspecific nephrotoxic effects on cell metabolism and Na-K-ATPase activity rather than through its specific interaction with the organic anion transport system.
D000251:Adenosine Triphosphatases / Q000378:metabolism; D000618:Aminohippuric Acids / Q000378:metabolism*; D000818:Animals; D017301:Ca(2+) Mg(2+)-ATPase; D006072:Gossypol / Q000494:pharmacology*; D066298:In Vitro Techniques; D007672:Kidney Cortex / Q000187:drug effects* / Q000378:metabolism; D008861:Microsomes / Q000187:drug effects / Q000201:enzymology; D010101:Oxygen Consumption; D011817:Rabbits; D000254:Sodium-Potassium-Exchanging ATPase / Q000378:metabolism; D013757:Tetraethylammonium Compounds / Q000378:metabolism; D010130:p-Aminohippuric Acid / Q000378:metabolism*
D000618:Aminohippuric Acids; D013757:Tetraethylammonium Compounds; D000251:Adenosine Triphosphatases; D017301:Ca(2+) Mg(2+)-ATPase; D000254:Sodium-Potassium-Exchanging ATPase; D006072:Gossypol; D010130:p-Aminohippuric Acid