Na+-dependent and Na+-independent betaine transport across the apical membrane of rat renal epithelium

Abstract

The low renal excretion of betaine indicates that the kidney efficiently reabsorbs the betaine filtered by the glomeruli but the mechanisms involved in such a process have been scarcely investigated. We have detected concentrative and non-concentrative betaine transport activity in brush-border membrane vesicles (BBMV) from rat renal cortex and medulla. The concentrative system is the Sodium/Imino-acid Transporter 1 (SIT1) because it is Na+- and Cl−-dependent, electrogenic and is inhibited by an anti-SIT1 antibody. Its apparent affinity constant for betaine, Kt, is 1.1±0.5mM and its maximal transport velocity, Vmax, 0.5±0.1nmol betaine/mg protein/s. Inhibitors of the Na+/Cl−/betaine uptake are l-proline (75%) and cold betaine, l-carnitine and choline (40–60%). Neither creatine, TEA, taurine, β-alanine, GABA nor glycine significantly inhibited Na+/Cl−/betaine uptake. The non-concentrative betaine transport system is Na+- and H+-independent, electroneutral, with a Kt for betaine of 47±7μM and a Vmax of 7.8±1 pmol betaine/mg protein/s. Its transport activity is nearly abolished by betaine, followed by l-carnitine (70–80%) and proline (40–50%), but a difference from the Na+/Cl−/betaine transport is that it is inhibited by TEA (approx. 50%) and unaffected by choline. The underlying carrier functions as an antiporter linking betaine entry into the BBMV with the efflux of either l-carnitine or betaine, an exchange unaffected by the anti-SIT1 antibody. As far as we know this is the first work reporting that betaine crosses the apical membrane of rat renal epithelium by SIT1 and by a Na+- and H+-independent transport system.