Transport of paraquat by isolated renal proximal tubular segments from rabbits.
Paraquat is a non-selective herbicide, which induces lung, liver and kidney damage in mammalian species. Because paraquat is mainly eliminated by the kidneys, the induced kidney damage may suppress excretion and enhance toxicity of paraquat in other organs. Since proximal tubules appear to be the target segment of the nephron, this study focuses on transport of paraquat by isolated proximal tubular segments from rabbits. Proximal tubules were isolated using a combined magnetic iron perfusion and collagenase method. Incubations were carried out at 25 degrees under 100% oxygen or nitrogen for varying times at different concentrations of paraquat. Proximal tubules accumulated paraquat by a slow process, which was non-saturable in the concentration range (0.1-5 microM) examined. Tubular excretion of cations involves transport across both basolateral and luminal membranes of the cell. The basolateral uptake of paraquat was inhibited by low temperature, low medium pH and quinine. In contrast to quinine, tetraethylammonium enhanced paraquat accumulation probably by trans-stimulating the basolateral uptake. Incubation under nitrogen enhanced paraquat accumulation possibly by reducing the transport out of the cell at the luminal membrane. Thus, this study shows that proximal tubules accumulate paraquat by an active process related to the cation transport mechanism.
Mølck
A M
AM
Department of Pharmacology and Pathobiology, Royal Veterinary and Agricultural University, Frederiksberg, Denmark.
Friis
C
C
D000818:Animals; D001693:Biological Transport, Active / Q000187:drug effects; D005260:Female; D006540:Herbicides / Q000493:pharmacokinetics*; D006863:Hydrogen-Ion Concentration; D066298:In Vitro Techniques; D007425:Intracellular Membranes / Q000378:metabolism; D007687:Kidney Tubules, Proximal / Q000378:metabolism*; D008297:Male; D010269:Paraquat / Q000493:pharmacokinetics*; D011803:Quinine / Q000494:pharmacology; D011817:Rabbits; D012964:Sodium / Q000494:pharmacology; D013696:Temperature; D019789:Tetraethylammonium / Q000494:pharmacology
D006540:Herbicides; D019789:Tetraethylammonium; D012964:Sodium; D011803:Quinine; D010269:Paraquat