title: Nateglinide uptake by a ceftibuten transporter in the rat kidney brush-border membrane.
abstract: Nateglinide, a novel oral hypoglycemic agent, possesses a carbonyl group and a peptide-type bond in its structure. We previously reported that nateglinide transport occurs via a single system that may be identical to the ceftibuten/H(+) cotransport system by the rat small intestine. We speculated that the absorption system present on the intestinal epithelium may be similar to that found on the renal tubular epithelium. The aim of this study was to characterize the transporters on the apical side of the kidney that may contribute to the reabsorption of ceftibuten and nateglinide. The uptake of nateglinide by rat renal brush-border membranes is associated with an H(+)-coupled transport system. Ceftibuten competitively inhibited H(+)-dependent nateglinide uptake. In contrast, Gly-Sar, cephradine and cephalexin had no effect on nateglinide uptake. Nateglinide competitively inhibited H(+)-driven transporter-mediated ceftibuten uptake. We conclude that nateglinide transport occurs via a single system that is H(+)-dependent and may be identical to the ceftibuten/H(+) cotransport system.
authors.affiliation: Department of Clinical Pharmaceutics and Therapeutics, Graduate School of Pharmaceutical Sciences, Hokkaido University, Kita-12jo, Nishi-6-chome, Kita-ku, Sapporo 060-0812, Japan.
authors.forename: Masaki
authors.initials: M
authors.lastname: Kobayashi
authors.forename: Yoshitaka
authors.initials: Y
authors.lastname: Saito
authors.forename: Shirou
authors.initials: S
authors.lastname: Itagaki
authors.forename: Takeshi
authors.initials: T
authors.lastname: Hirano
authors.forename: Ken
authors.initials: K
authors.lastname: Iseki
mesh_terms: D000818:Animals; D000077722:Ceftibuten; D002511:Cephalosporins / Q000378:metabolism* / Q000494:pharmacology; D003510:Cyclohexanes / Q000378:metabolism*; D017136:Ion Transport / Q000187:drug effects; D007668:Kidney / Q000378:metabolism* / Q000648:ultrastructure; D008297:Male; D008871:Microvilli / Q000378:metabolism*; D000077715:Nateglinide; D000074011:Peptide Transporter 1; D010649:Phenylalanine / Q000031:analogs & derivatives* / Q000378:metabolism; D011522:Protons; D051381:Rats; D017208:Rats, Wistar; D027981:Symporters / Q000378:metabolism
chemical_list: D002511:Cephalosporins; D003510:Cyclohexanes; D000074011:Peptide Transporter 1; D011522:Protons; C489940:Slc15a1 protein, rat; D027981:Symporters; D000077715:Nateglinide; D010649:Phenylalanine; D000077722:Ceftibuten