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.