ACCUMULATION OF NATURAL AND SYNTHETIC BETAINES BY A MAMMALIAN RENAL-CELL LINE

Intracellular accumulation of different betaines was compared in osmot ically stressed Madin Darby canine kidney (MDCK) cells to model the be taine accumulation specificity of the mammalian inner medulla and to s how how this accumulation differed from that of bacteria. All betaines accumulated less than glycine betaine. Arsenobetaine (the arsenic ana logue of glycine betaine) accumulated to 12% of the glycine betaine le vels and the sulphur analogue dimethylthetin accumulated to >80%. Most substituted glycine betaine analogues accumulated to 2-5% of intracel lular glycine betaine concentrations, however, serine betaine accumula ted to <0.5% of glycine betaine levels. Inhibition studies to distingu ish the betaine ports were performed by the addition of proline. Butyr obetaine and carnitine accumulation was not proline sensitive, whereas that of other betaines was. As with glycine betaine, the accumulation of propionobetaine and dimethylthetin was proline sensitive and osmor egulated. Pyridinium betaine was accumulated by both proline-sensitive and -insensitive systems, with a small increase under osmotic stress. High concentrations (IO times that of glycine betaine) of the dietary betaines proline betaine and trigonelline inhibited total betaine acc umulation. Because alpha-substituted betaines are accumulated by bacte ria and not by MDCK cells, these betaines may be the basis for design of antimicrobial agents.