Interaction of paraquat and amine uptake by rat lungs perfused in situ.
The kinetics of [14C]paraquat (N,N-di[14C]methyl-4,4'-bipyridylium) uptake from the pulmonary circulation were investigated in rat lungs perfused in situ. During the 1st h of exposure to the herbicide paraquat entered the lungs primarily by diffusion; no evidence was obtained from concentrative uptake, saturation kinetics (1-3,500 microM paraquat), or inhibition by the amines methyl-glyoxal bis(guanylhydrazone) or spermidine, both of which were expected to compete for paraquat transport sites. In contrast, after 60 min of exposure, uptake rates increased two- to three-fold, and paraquat was accumulated to an apparent intracellular concentration greater than that in the perfusate. The latter phase of paraquat uptake was saturable and was inhibited by methylglyoxal bis(guanylhydrazone); it did not appear to reflect a progressive paraquat-induced alteration in cellular permeability but rather predominance of a rapid, carrier-mediated uptake pathway.
D000818:Animals; D004347:Drug Interactions; D007700:Kinetics; D008168:Lung / Q000378:metabolism*; D008297:Male; D008935:Mitoguazone / Q000378:metabolism* / Q000494:pharmacology; D010269:Paraquat / Q000037:antagonists & inhibitors / Q000378:metabolism*; D010477:Perfusion; D051381:Rats; D013095:Spermidine / Q000378:metabolism* / Q000494:pharmacology
D008935:Mitoguazone; D010269:Paraquat; D013095:Spermidine