PT  - JOURNAL ARTICLE
AU  - Rosalinde Masereeuw
AU  - Miek M. Moons
AU  - Barbara H. Toomey
AU  - Frans G. M. Russel
AU  - David S. Miller
TI  - Active Lucifer Yellow Secretion in Renal Proximal Tubule: Evidence for Organic Anion Transport System Crossover
DP  - 1999 May 01
TA  - Journal of Pharmacology and Experimental Therapeutics
PG  - 1104--1111
VI  - 289
IP  - 2
4099  - http://jpet.aspetjournals.org/content/289/2/1104.short
4100  - http://jpet.aspetjournals.org/content/289/2/1104.full
SO  - J Pharmacol Exp Ther1999 May 01; 289
AB  - Recent studies show that organic anion secretion in renal proximal tubule is mediated by distinct sodium-dependent and sodium-independent transport systems. Here we investigated the possibility that organic anions entering the cells on one system can exit into the lumen on a transporter associated with the other system. In isolated rat kidneys perfused with 10 μM lucifer yellow (LY, a fluorescent organic anion) plus 100 μg/ml inulin, the LY-to-inulin clearance ratio averaged 1.6 ± 0.2, indicating net tubular secretion. Probenecid significantly reduced both LY clearance and LY accumulation in kidney tissue. In intact killifish proximal tubules, confocal microscopy was used to measure steady-state LY uptake into cells and secretion into the tubular lumen. Probenecid, p-aminohippurate, and ouabain nearly abolished both uptake and secretion. To this point, the data indicated that LY was handled by the sodium-dependent and ouabain-sensitive organic anion transport system. However, leukotriene C4, an inhibitor of the luminal step for the sodium-independent and ouabain-insensitive organic anion system, reduced luminal secretion of LY by 50%. Leukotriene C4 did not affect cellular accumulation of LY or the transport of fluorescein on the sodium-dependent system. A similar inhibition pattern was found for another fluorescent organic anion, a mercapturic acid derivative of monochlorobimane. Thus, both organic anions entered the cells on the basolateral transporter for the classical, sodium-dependent system, but about half of the transport into the lumen was handled by the luminal carrier for the sodium-independent system, which is most likely the multidrug resistance-associated protein. This is the first demonstration that xenobiotics can enter renal proximal tubule cells on the carrier associated with one organic anion transport system and exit into the tubular lumen on multiple carriers, one of which is associated with a second system. The American Society for Pharmacology and Experimental Therapeutics