STEREOSELECTIVE UPTAKE OF AN ORGANIC ANION ACROSS THE RENAL BASOLATERAL MEMBRANE IN ISOLATED-PERFUSED RAT-KIDNEY

To clarify which process in renal secretion is responsible for the ste reoselective renal secretion of organic anions, the renal handling of enantiomers of yl-6,7-dichloro-2,3-dihydrobenzofuran-2-carboxylic acid (MBCA) was studied by the multiple-indicator dilution method, using i solated perfused rat kidney. After bolus injection of (R)-(+)-[C-14]MB CA or (S)-(-)-[C-14]MBCA into the renal artery, the outflow patterns f or the perfusate and the urinary excretion rate profiles were estimate d by statistical moment analysis. AUC values and mean transit times in kidney for the MBCA enantiomers indicated that (R)-(+)-MBCA was excre ted much more extensively in urine and that it had a higher affinity f or renal tissue than did (S)-(-)-MBCA. A significantly larger intrinsi c clearance of secretion for (R)-(+)-MBCA attested to the R-(+)-prefer ential renal secretion. The uptake rate constant across the basolatera l membrane, the ratio of the uptake rate constant to the free fraction in the perfusate, and the intracellular distribution volume were sign ificantly larger for (R)-(+)-MBCA than for (S)-(-)-MBCA, indicating th at uptake across the basolateral membrane and intracellular distributi on were R-(+)-preferential, However, the mean time across renal epithe lial cells for secreted molecules, the single-pass mean residence time in renal epithelial cells, and the rate constant for secretion across the brush-border membrane were not significantly different between en antiomers. The simultaneous presence of (R)-(+)-MBCA decreased the int rinsic clearance of secretion, the ratio of the uptake rate constant t o the free fraction in the perfusate, and the intracellular distributi on volume for (S)-(-)-[C-14]MBCA, although the secretion rate constant , the mean time across renal epithelial cells for secreted molecules, and the single-pass mean residence time in renal epithelial cells were not influenced by (R)-(+)-MBCA, confirming that uptake across the bas olateral membrane and intracellular distribution were stereoselective processes.