Inhibitory effect of anti-diabetic agents on rat organic anion transporter rOAT1.

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Uwai Y, Saito H, Hashimoto Y, Inui K

Inhibitory effect of anti-diabetic agents on rat organic anion transporter rOAT1.

Eur J Pharmacol. 2000 Jun 16;398(2):193-7.

PubMed ID

10854830 [ View in PubMed

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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.

DrugBank Data that Cites this Article

Drug Transporters

Drug	Transporter	Kind	Organism	Pharmacological Action	Actions
Chlorpropamide	Solute carrier family 22 member 6	Protein	Humans	Unknown	Inhibitor	Details
Glyburide	Solute carrier family 22 member 6	Protein	Humans	Unknown	Inhibitor	Details
Nateglinide	Solute carrier family 22 member 6	Protein	Humans	Unknown	Inhibitor	Details
Tolbutamide	Solute carrier family 22 member 6	Protein	Humans	Unknown	Inhibitor	Details