Uptake of ochratoxin A by slices of pig kidney cortex

Ochratoxin A (OCT A) is a nephrotoxin causing selective necrosis of the proximal tubule. Being an organic anion OCT A might be expected to enter the tubule cells by the organic anion transport system. Pig renal cortical slices were used to characterize the OCT A transport. OCT A (5 X 10(-3) mM) was accumulated against a concentration gradient with a slice to medium ratio of 8.9 +/- 2.9 in the presence of oxygen. This accumulation was markedly reduced in a nitrogen atmosphere (S/M ratio = 2.9 +/- 0.5). OCT A accumulation was dependent on medium concentration. With increasing concentration (5 X 10(-4)-5 X 10(-1) mM), slice to medium ratio initially rose from 6.9 +/- 2.0 to 11.7 +/- 1.2 whereupon it declined to 5.4 +/- 1.1. This pattern indicates that both carrier mediated transport and intracellular metabolism may contribute to the net accumulation of the toxin. OCT A (10(-4) to 1 mM) inhibited p-aminohippurate (PAH) and phenolsulphophthalein (PSP) uptake in a dose-dependent manner. Up to 10(-1) mM, OCT A did not inhibit acetylation of PAH suggesting that aerobic metabolism and the energy supply for the transport process were unaffected. Kinetic studies revealed a competitive inhibition of the PSP transport. It is concluded that OCT A enters the proximal tubule cells by the common organic anion transport system.