Inhibitory Effects of 17-α-Ethinyl-Estradiol and 17-β-Estradiol on Transport Via the Intestinal Proton-Coupled Amino Acid Transporter (PAT1) Investigated In Vitro and In Vivo
| Autor: | Maria Pedersen, Maria Bjerg, Salli Nielsen, Martha Kampp Nøhr, Stephanie Müller, René Holm, Nithiya Ulaganathan, Carsten Uhd Nielsen, Thea Kaestel, Krestine Lundgaard Carlsen |
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| Rok vydání: | 2020 |
| Předmět: |
Male
Taurine Amino Acid Transport Systems Pharmaceutical Science 02 engineering and technology Pharmacology DRUG SUBSTANCE VIGABATRIN 030226 pharmacology & pharmacy Intestinal absorption NA+/H+ EXCHANGE Rats Sprague-Dawley chemistry.chemical_compound 0302 clinical medicine ABSORPTION Serotonin transporter AFFINITY biology Estradiol Symporters BRUSH-BORDER MEMBRANE H+ 021001 nanoscience & nanotechnology 17-β-estradiol SLC36A1 Protons 0210 nano-technology medicine.drug EXPRESSION Inhibitor DDI 03 medical and health sciences 17-beta-estradiol In vivo 17-alpha-ethinyl-estradiol (E-E2) medicine Animals Humans Amino acid transporter Proline PAT (SLC36A1) fungi HPAT1 Transporter 17-α-ethinyl-estradiol (E-E2) Caco-2 Biological Transport Rats chemistry Intestinal Absorption biology.protein Caco-2 Cells Gaboxadol SYSTEM |
| Zdroj: | Nielsen, C U, Pedersen, M, Muller, S, Kaestel, T, Bjerg, M, Ulaganathan, N, Nielsen, S, Carlsen, K L, Nohr, M K & Holm, R 2021, ' Inhibitory Effects of 17-alpha-Ethinyl-Estradiol and 17-beta-Estradiol on Transport Via the Intestinal Proton-Coupled Amino Acid Transporter (PAT1) Investigated In Vitro and In Vivo ', Journal of Pharmaceutical Sciences, vol. 110, no. 1, pp. 354-364 . https://doi.org/10.1016/j.xphs.2020.08.010 Nielsen, C U, Pedersen, M, Müller, S, Kæstel, T, Bjerg, M, Ulaganathan, N, Nielsen, S, Lundgaard Carlsen, K, Nøhr, M K & Holm, R 2021, ' Inhibitory effects of 17-α-ethinyl-estradiol and 17-β-estradiol on transport via the intestinal proton-coupled amino acid transporter (PAT1) investigated In vitro and in vivo ', Journal of Pharmaceutical Sciences, vol. 110, no. 1, pp. 354-364 . https://doi.org/10.1016/j.xphs.2020.08.010 |
| ISSN: | 1520-6017 |
| Popis: | The proton-coupled amino acid transporter, PAT1, is known to be responsible for intestinal absorption drug substances such as gaboxadol and vigabatrin. The aim of the present study was to investigate, if 17-alpha-ethinyl-estradiol (E-E2) and 17-beta-estradiol (E) inhibit PAT1-mediated intestinal absorption of proline and taurine in vitro in Caco-2 cells and in vivo using Sprague-Dawley rats to assess the potential for taurine-drug interactions. E and E-E2 inhibited the PAT1-mediated uptake of proline and taurine in Caco-2 cells with IC50 values of 10.0-50.0 mu M without major effect on other solute carriers such as the taurine transporter (TauT), di/tri-peptide transporter (PEPT1), and serotonin transporter (SERT1). In PAT1-expressing oocytes E and E-E2 were non-translocated inhibitors. In Caco-2 cells, E and E-E2 lowered the maximal uptake capacity of PAT1 in a non-competitive manner. Likewise, the transepithelial permeability of proline and taurine was reduced in presence of E and E-E2. In male Sprague Dawley rats pre-dosed with E-E2 a decreased maximal plasma concentration (C-max) of taurine and increased the time (t(max)) to reach this was indicated, suggesting the possibility for an in vivo effect on the absorption of PAT1 substrates. In conclusion, 17-alpha-ethinyl-estradiol and 17-beta-estradiol were identified as non-translocated and non-competitive inhibitors of PAT1. (C) 2020 American Pharmacists Association (R). Published by Elsevier Inc. All rights reserved. |
| Databáze: | OpenAIRE |
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