TY - JOUR
T1 - Interaction characteristics of flavonoids with human organic anion transporter 1 (hOAT1) and 3 (hOAT3)
AU - Hong, Soon Sun
AU - Seo, Kisoo
AU - Lim, Sung Chul
AU - Han, Hyo Kyung
PY - 2007/12
Y1 - 2007/12
N2 - The present study aimed to investigate the interaction characteristics of flavonoids with human organic anion transporter 1 (hOAT1) and 3 (hOAT3). Five flavonoids (morin, silybin, naringin, naringenin and quercetin) were selected and their interaction characteristics with hOAT1 and hOAT3 were examined in MDCK cells overexpressing hOAT1 or hOAT3. Among tested flavonoids, morin and silybin exhibited significant inhibition effects on the cellular uptake of [3H]-para-aminohippuric acid ([3H]-PAH) in MDCK-hOAT1 cells with Ki of 0.46 μM and 24 μM, respectively, while all the tested flavonoids appeared to be less interactive with hOAT3 compared to hOAT1. A kinetic study suggested that morin and silybin inhibited hOAT1-mediated cellular uptake of [3H]-PAH in a competitive manner. Furthermore, morin and silybin were translocated by hOAT1 across the cellular membrane. In conclusion, the present study identified some of flavonoids as a new class of hOAT1 inhibitors, suggesting a potential for flavonoid-drug interactions via the modulation of hOAT1 activity.
AB - The present study aimed to investigate the interaction characteristics of flavonoids with human organic anion transporter 1 (hOAT1) and 3 (hOAT3). Five flavonoids (morin, silybin, naringin, naringenin and quercetin) were selected and their interaction characteristics with hOAT1 and hOAT3 were examined in MDCK cells overexpressing hOAT1 or hOAT3. Among tested flavonoids, morin and silybin exhibited significant inhibition effects on the cellular uptake of [3H]-para-aminohippuric acid ([3H]-PAH) in MDCK-hOAT1 cells with Ki of 0.46 μM and 24 μM, respectively, while all the tested flavonoids appeared to be less interactive with hOAT3 compared to hOAT1. A kinetic study suggested that morin and silybin inhibited hOAT1-mediated cellular uptake of [3H]-PAH in a competitive manner. Furthermore, morin and silybin were translocated by hOAT1 across the cellular membrane. In conclusion, the present study identified some of flavonoids as a new class of hOAT1 inhibitors, suggesting a potential for flavonoid-drug interactions via the modulation of hOAT1 activity.
KW - Cellular uptake
KW - Flavonoids
KW - Human organic anion transporter 1 (hOAT1)
KW - Human organic anion transporter 3 (hOAT3)
KW - Inhibition
UR - http://www.scopus.com/inward/record.url?scp=36249009108&partnerID=8YFLogxK
U2 - 10.1016/j.phrs.2007.08.007
DO - 10.1016/j.phrs.2007.08.007
M3 - Article
C2 - 17920288
AN - SCOPUS:36249009108
SN - 1043-6618
VL - 56
SP - 468
EP - 473
JO - Pharmacological Research
JF - Pharmacological Research
IS - 6
ER -