title: Inhibitory effect of anti-diabetic agents on rat organic anion transporter rOAT1.
abstract: The interactions of sulfonylureas and a novel anti-diabetic drug, nateglinide, with rat renal organic anion transporter (rOAT1) expressed in Xenopus laevis oocytes were studied. Uptake of p-aminohippurate via rOAT1 was markedly inhibited by glibenclamide and nateglinide, and moderately by chlorpropamide and tolbutamide. The inhibition constant values (K(i)) for chlorpropamide, glibenclamide, tolbutamide and nateglinide were 39.5, 1.6, 55.5 and 9.2 microM, respectively. Kinetic analysis showed that the inhibition of p-aminohippurate uptake by glibenclamide was competitive. Sulfonylureas examined and nateglinide did not show a trans-stimulation effect on [14C]p-aminohippurate efflux from rOAT1-expressing oocytes. There was no stimulation of [3H]glibenclamide uptake via rOAT1. These findings suggested that sulfonylureas and nateglinide interact with rOAT1, but these drugs are not translocated via the transporter.
authors.affiliation: Department of Pharmacy, Kyoto University Hospital, Faculty of Medicine, Kyoto University, Sakyo-ku, 606-8507, Kyoto, Japan.
authors.forename: Y
authors.initials: Y
authors.lastname: Uwai
authors.forename: H
authors.initials: H
authors.lastname: Saito
authors.forename: Y
authors.initials: Y
authors.lastname: Hashimoto
authors.forename: K
authors.initials: K
authors.lastname: Inui
mesh_terms: D000818:Animals; D027321:Anion Transport Proteins; D001667:Binding, Competitive / Q000187:drug effects; D002250:Carbon Radioisotopes; D002352:Carrier Proteins / Q000037:antagonists & inhibitors* / Q000235:genetics / Q000378:metabolism; D002747:Chlorpropamide / Q000494:pharmacology; D003510:Cyclohexanes / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D005260:Female; D005905:Glyburide / Q000494:pharmacology; D007004:Hypoglycemic Agents / Q000494:pharmacology*; D007700:Kinetics; D000077715:Nateglinide; D009865:Oocytes; D010649:Phenylalanine / Q000031:analogs & derivatives* / Q000494:pharmacology; D018075:RNA, Complementary / Q000008:administration & dosage / Q000235:genetics; D051381:Rats; D013453:Sulfonylurea Compounds / Q000494:pharmacology; D014044:Tolbutamide / Q000494:pharmacology; D014981:Xenopus; D010130:p-Aminohippuric Acid / Q000378:metabolism / Q000493:pharmacokinetics
chemical_list: D027321:Anion Transport Proteins; D002250:Carbon Radioisotopes; D002352:Carrier Proteins; D003510:Cyclohexanes; D007004:Hypoglycemic Agents; D018075:RNA, Complementary; D013453:Sulfonylurea Compounds; D000077715:Nateglinide; D010649:Phenylalanine; D014044:Tolbutamide; D005905:Glyburide; D002747:Chlorpropamide; D010130:p-Aminohippuric Acid