2020 年 46 巻 1 号 p. 38-43
We have recently found the H+/quinidine (QND) antiport system in canine kidney MDCK, porcine kidney LLC-PK1, and human embryonic kidney (HEK) 293 cells. The aim of the present study was to explore the biological materials responsible for an H+/lipophilic cation antiport system in renal tubular cells. We prepared phosphatidyl choline (PC) liposomes and phosphatidyl serine (PS)-containing PC/PS liposomes, and investigated the uptake of lipophilic organic cations.The uptake of 100 µM bisoprolol (BIS) into PC and PC/PS liposomes was increased by the alkalization of medium pH, and the uptake of the drug into PC/PS liposomes was significantly greater than that into PC liposomes. In addition, a lipophilic cationic drug, diphenhydramine (DPH), significantly decreased the BIS uptake in PC/PS liposomes. The Michaelis-Menten constant (Km) for BIS was lower in PC/PS liposomes than in PC liposomes.The uptake of 11 cationic compounds (celiprolol, acebutolol, procainamide, pindolol, BIS, metoprolol, flecainide, clonidine, pyrilamine, QND, and propranolol) into PC/PS liposomes, as well as that into HEK293 cells, was positively correlated with their lipophilicity (Log D) values, and tended to be negatively correlated with their polar surface area (Log PSA) values. These findings suggest that phospholipids are, at least partly, responsible for the postulated H+/lipophilic cation antiport system in the kidney.
