RRC ID 62248
Author Furumiya M, Yamashiro T, Inoue K, Nishijima C, Ohta K, Hayashi Y, Yuasa H.
Title Sustained inhibition of proton-coupled folate transporter by myricetin.
Journal Drug Metab Pharmacokinet
Abstract Myricetin is a flavonoid that has recently been suggested to interfere with the intestinal folate transport system. To examine that possibility, focusing on its sustained inhibitory effect on proton-coupled folate transporter (PCFT), the uptake of folate was examined in Caco-2 cells, in which PCFT is known to be in operation, in the absence of myricetin in the medium during uptake period after preincubation of the cells with the flavonoid (100 μM) for 1 h. This pretreatment induced an extensive and sustained reduction in the carrier-mediated component of folate uptake, which was attributable to a reduction in the maximum transport rate (Vmax). Although the affinity of the transporter for folate was increased at the same time as indicated by a reduction in the Michaelis constant (Km), the change in Km was overwhelmed in extent by that in Vmax. Consistent with the finding, folate transport by human PCFT stably expressed in Madin-Darby canine kidney II cells was reduced in a similar manner with simultaneous reductions in Vmax and Km by myricetin pretreatment. Attention may need to be given for a possibility that such a sustained inhibition of PCFT could potentially be a cause of the malabsorption of folate and also antifolate drugs.
Volume 30(2)
Pages 154-9
Published 2015-4-1
DOI 10.1016/j.dmpk.2014.11.001
PII S1347-4367(14)00020-2
PMID 25801697
MeSH Animals Biological Transport Caco-2 Cells Dogs Dose-Response Relationship, Drug Flavonoids / pharmacology* Folic Acid / metabolism* Humans Intestinal Absorption / drug effects* Intestinal Mucosa / drug effects* Intestinal Mucosa / metabolism Kinetics Madin Darby Canine Kidney Cells Models, Biological Proton-Coupled Folate Transporter / antagonists & inhibitors* Proton-Coupled Folate Transporter / genetics Proton-Coupled Folate Transporter / metabolism Transfection
IF 2.772
Human and Animal Cells CACO-2(RCB0988)