TY - JOUR
T1 - Inhibitory effect of anti-diabetic agents on rat organic anion transporter rOAT1
AU - Uwai, Yuichi
AU - Saito, Hideyuki
AU - Hashimoto, Yukiya
AU - Inui, Ken Ichi
N1 - Funding Information:
This work was supported in part by a Grant-in-Aid for Scientific Research from the Ministry of Education, Science, Sports, and Culture of Japan, the Yamanouchi Foundation on Metabolic Disorders, and the Uehara Memorial Foundation.
PY - 2000/6/16
Y1 - 2000/6/16
N2 - 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 μM, 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. Copyright (C) 2000 Elsevier Science B.V.
AB - 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 μM, 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. Copyright (C) 2000 Elsevier Science B.V.
KW - Nateglinide
KW - OAT1 (organic anion transporter 1)
KW - Renal tubular secretion
KW - Sulfonylurea
KW - Xenopus oocytes
KW - p-Aminohippurate
UR - http://www.scopus.com/inward/record.url?scp=0034674381&partnerID=8YFLogxK
U2 - 10.1016/S0014-2999(00)00324-1
DO - 10.1016/S0014-2999(00)00324-1
M3 - 学術論文
C2 - 10854830
AN - SCOPUS:0034674381
SN - 0014-2999
VL - 398
SP - 193
EP - 197
JO - European Journal of Pharmacology
JF - European Journal of Pharmacology
IS - 2
ER -
