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 μM paraquat), or inhibition by the amines methylglyoxal 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 threefold, 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.