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• W2162210366 abstract "Organic anion transporting polypeptide (Oatp) 1c1 is a high-affinity T4 transporter with narrow substrate specificity expressed at the blood-brain barrier. A transport model using cells overexpressing Oatp1c1 was created to identify novel Oatp1c1 substrates and inhibitors. Rat Oatp1c1 was cloned and stably expressed in human embryonic kidney 293 cells. Oatp1c1-transfected human embryonic kidney 293 cells transported 125I-labeled T4 in a time-dependent manner that was completely abolished in the presence of excess unlabeled T4. Next, various compounds, including inhibitors of thyroid hormone uptake, were screened for inhibitory effects on Oatp1c1-mediated T4 uptake. Phenytoin (64%), indocyanine green (17%), fenamic acid (68%), diclofenac (51%), and meclofenamic acid (33%) all reduced T4 uptake by Oatp1c1 when assayed at concentrations of 10 μM. Dose-response assays for the fenamic acids, iopanoic acid, indocyanine green, and phenytoin revealed IC50 values for Oatp1c1 T4 uptake below or near the blood plasma levels after therapeutic doses. Further kinetic assays and reciprocal plot analyses demonstrated that the fenamic acid diclofenac inhibited in a competitive manner. Finally, microvessels were isolated from adult rat brain and assessed for T4 uptake. Ten micromolar of fenamate concentrations inhibited T4 microvessel uptake with a similar hierarchical inhibition profile [fenamic acid (43%), diclofenac (78%), and meclofenamic acid (85%)], as observed for Oatp1c1 transfected cells. Oatp1c1 is expressed luminally and abluminally in the blood-brain barrier endothelial cell, and exhibits bidirectional transport capabilities. Together, these data suggest that Oatp1c1 transports fenamates into, and perhaps across, brain barrier cells. The fenamate class of nonsteroidal anti-inflammatory drugs is transported by organic anion transporting polypeptides and competitively inhibits thyroxine transport in brain microvessels." @default.
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• W2162210366 date "2009-02-01" @default.
• W2162210366 modified "2023-10-14" @default.
• W2162210366 title "Competitive Inhibition of Organic Anion Transporting Polypeptide 1c1-Mediated Thyroxine Transport by the Fenamate Class of Nonsteroidal Antiinflammatory Drugs" @default.
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• W2162210366 doi "https://doi.org/10.1210/en.2008-0188" @default.
• W2162210366 hasPubMedCentralId "https://www.ncbi.nlm.nih.gov/pmc/articles/2646527" @default.
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