Carnitine transport acid its inhibition by sulfonylureas in human kidney proximal tubular epithelial cells

The kidney plays an important role in the homeostasis of carnitine by its a bility to reabsorb carnitine almost completely from the glomerular filtrate . The transport process responsible for this reabsorption has been investig ated thus far only in laboratory animals. Here we report on the characteris tics of carnitine uptake in a proximal tubular epithelial cell line derived from human kidney. The uptake process was found to be obligatorily depende nt on Na+ with no involvement of anions. The process was saturable, with a Michaelis-Menten constant of 14 +/- 1 mu M. The Na+:carnitine stoichiometry was 1:1. The same process also was found to be responsible for the uptake of acetylcarnitine and propionylcarnitine, two acyl esters of carnitine wit h potential for therapeutic use in humans. The uptake process was specific for carnitine and its acyl esters. Betaine, a structural analog of carnitin e, interacted with the uptake process to a significant extent. The present studies also showed that sulfonylureas, oral hypoglycemic agents currently used in the management of type 2 diabetes, inhibited the carnitine uptake s ystem. Among the sulfonylureas tested, glibenclamide was the most potent in hibitor. The inhibition was competitive. Glibenclamide inhibited the uptake not only of carnitine but also of acetylcarnitine and propionylcarnitine. The inhibition most likely was the result of direst interaction of the comp ound with the carnitine transporter because the inhibition could be demonst rated in purified rat kidney brush border membrane vesicles. (C) 1999 Elsev ier Science Inc.