Interaction of paraquat and amine uptake by rat lungs perfused in situ

The kinetics of ( super(14)C)paraquat (N,N-di( super(14)C)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 mu M paraquat), or inhibition by the amines methylglyoxal bis(guanylhydrazone) or spermidine, both of which were expected to compete for paraquat transport sites. After 60 min of exposure, uptake rates increased two- to three-fold, and paraquate 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 predominance of a rapid, carrier-mediated uptake pathway.