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

Abstract：

:The kidney plays an important role in the homeostasis of carnitine by its ability to reabsorb carnitine almost completely from the glomerular filtrate. The transport process responsible for this reabsorption has been investigated thus far only in laboratory animals. Here we report on the characteristics of carnitine uptake in a proximal tubular epithelial cell line derived from human kidney. The uptake process was found to be obligatorily dependent on Na+ with no involvement of anions. The process was saturable, with a Michaelis-Menten constant of 14 +/- 1 microM. 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 with potential for therapeutic use in humans. The uptake process was specific for carnitine and its acyl esters. Betaine, a structural analog of carnitine, 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 system. Among the sulfonylureas tested, glibenclamide was the most potent inhibitor. 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 direct interaction of the compound with the carnitine transporter because the inhibition could be demonstrated in purified rat kidney brush border membrane vesicles.

journal_name

Biochem Pharmacol

journal_title

Biochemical pharmacology

authors

Huang W,Shaikh SN,Ganapathy ME,Hopfer U,Leibach FH,Carter AL,Ganapathy V

doi

10.1016/s0006-2952(99)00219-1

subject

Has Abstract

pub_date

1999-10-15 00:00:00

pages

1361-70

issue

8

eissn

0006-2952

issn

1873-2968

pii

S0006-2952(99)00219-1

journal_volume

58

pub_type

杂志文章

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