Functional characteristics of a renal H+/lipophilic cation antiport system in porcine LLC-PK1 cells and rats.

We have recently found an H+/quinidine (a lipophilic cation, QND) antiport system in Madin-Darby canine kidney (MDCK) cells. The primary aim of the present study was to evaluate whether the H+/lipophilic cation antiport system is expressed in porcine LLC-PK1 cells. That is, we investigated uptake and/or efflux of QND and another cation, bisoprolol, in LLC-PK1 cells. In addition, we studied the renal clearance of bisoprolol in rats. Uptake of QND into LLC-PK1 cells was decreased by acidification of the extracellular pH or alkalization of the intracellular pH. Cellular uptake of QND from the apical side was much greater than from the basolateral side. In addition, apical efflux of QND from LLC-PK1 cells was increased by acidification of the extracellular pH. Furthermore, lipophilic cationic drugs significantly reduced uptake of bisoprolol in LLC-PK1 cells. Renal clearance of bisoprolol in rats was approximately 7-fold higher than that of creatinine, and was markedly decreased by alkalization of the urine pH. The present study suggests that the H+/lipophilic cation antiport system is expressed in the apical membrane of LLC-PK1 cells. Moreover, the H+/lipophilic cation antiport system may be responsible for renal tubular secretion of bisoprolol in rats.

Presence of an H+/Quinidine Antiport System in Madin-Darby Canine Kidney Cells.

BACKGROUND AND OBJECTIVES: We have recently found an H+/quinidine antiport system in human kidney HEK 293 cells. The aim of the present study was to evaluate whether the H+/quinidine antiport system is expressed in Madin-Darby canine kidney (MDCK) cells. METHODS: We investigated the uptake and efflux of quinidine in MDCK cells. RESULTS: The uptake of 100 µM quinidine into MDCK cells was decreased by acidification of extracellular pH or alkalization of intracellular pH. In addition, the uptake of quinidine was highly temperature sensitive, but was extracellular Na+ and membrane potential independent. Furthermore, tetraethylammonium, a typical substrate of renal organic cation transporters, did not inhibit the uptake of quinidine in MDCK cells. On the other hand, lipophilic cationic drugs, such as clonidine, bisoprolol, diphenhydramine, pyrilamine, and imipramine, significantly decreased the uptake of quinidine in MDCK cells. The uptake of quinidine was saturable, and the Michaelis-Menten constant was estimated to be approximately 0.5 mM. In addition, the efflux of quinidine from MDCK cells was increased by the acidification of extracellular pH, suggesting that the transport system mediates not only the uptake, but also secretion of quinidine. CONCLUSIONS: The present findings suggested that the renal new antiport system is involved in the bidirectional membrane transport of quinidine in MDCK cells.