MATE1 sequesters organic cations within an intracellular, bafilomycin-sensitive compartment (892.39)

OC secretion across renal proximal tubules (RPTs) involves basolateral OCT2-mediated uptake from the blood, followed by apical MATE1/2-mediated efflux into the tubule filtrate. Whereas OCT2 is an electrogenic OC uniporter, MATE is an OC/H exchanger. Epifluorescence microscopy of hMATE1-expressing CHO cells revealed accumulation of the fluorescent OC, N,N,N-trimethyl-2-[methyl(7-nitrobenzo[c][l,2,5]oxadiazol-4-yl)amino]ethanaminium (NBD-MTMA) in the cytoplasm and in a smaller, punctate compartment; accumulation in OCT2 expressing cells was restricted to the cytoplasm. A second intracellular compartment was also evident in the multicompartmental kinetics of NBD-MTMA efflux from MATE1-CHO cells. Punctate accumulation (20 min) was markedly reduced by coexposure of MATE1-CHO cells with 1 μM bafilomycin (BAF) and eliminated with 10 μM BAF. BAF had no effect on the initial rate of MATE1-mediated uptake of NBD-MTMA (10-120 sec) suggesting that its effect involved collapse of endosomal pH gradients via inhibition ...