TRANSPORT OF PARAQUAT IN A RENAL EPITHELIAL-CELL LINE LLC-PK1

Transport of paraquat (PQ), a cationic herbicide, was investigated in a proximal renal epithelial cell line, LLC-PK1. Collagen coated permea ble filters were used to study the direction of PQ transport. PQ was t ransported predominantly from the basolateral to apical (B-->A) membra ne of these cells. The B-->A flux and uptake of PQ were saturable with time and increasing concentrations, energy dependent and inhibited by several cations. Quinine was the most potent inhibitor of basolateral PQ uptake, followed by cimetidine and then tetraethylammonium acetate (P < .0001). The noninhibitable basolateral uptake of PQ has an appar ent K-m of 357 mu M and a V-max of 1.47 pmol/mu g protein/2 min. For f lux studies, only quinine inhibited the B-->A flux of PQ (P = .02). Pu trescine, p-aminohippurate, probenecid, N-methylnicotinamide and choli ne did not inhibit the flux or uptake of PQ. 5-N,N-Hexamethylene amilo ride, a cationic amiloride analog and a potent inhibitor of the Na/H e xchanger, significantly inhibited the uptake of PQ from either side (P < .0001). Acidic pH in the apical medium inhibited the uptake of PQ f rom either side. The studies demonstrated that PQ was actively transpo rted by the LLC-PK1 cells. PQ shared a similar transport system with s everal cations, which appeared to have a more significant inhibition o n the transcellular uptake than the flux of PQ.