Trospium Chloride Transport by Mouse Drug Carriers of the Slc22 and Slc47 Families
Background: The muscarinic receptor antagonist trospium chloride (TCl) is used for pharmacotherapy of the overactive bladder syndrome. TCl is a hydrophilic positively charged drug. Therefore, it has low permeability through biomembranes and requires drug transporters for distribution and excretion....
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| Format: | Article |
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MDPI AG
2020-12-01
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| Series: | International Journal of Molecular Sciences |
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| Online Access: | https://www.mdpi.com/1422-0067/22/1/22 |
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| author | Matthias Gorecki Simon F. Müller Regina Leidolf Joachim Geyer |
| author_facet | Matthias Gorecki Simon F. Müller Regina Leidolf Joachim Geyer |
| author_sort | Matthias Gorecki |
| collection | DOAJ |
| description | Background: The muscarinic receptor antagonist trospium chloride (TCl) is used for pharmacotherapy of the overactive bladder syndrome. TCl is a hydrophilic positively charged drug. Therefore, it has low permeability through biomembranes and requires drug transporters for distribution and excretion. In humans, the organic cation transporters OCT1 and OCT2 and the multidrug and toxin extrusion MATE1 and MATE2-K carriers showed TCl transport. However, their individual role for distribution and excretion of TCl is unclear. Knockout mouse models lacking mOct1/mOct2 or mMate1 might help to clarify their role for the overall pharmacokinetics of TCl. Method: In preparation of such experiments, TCl transport was analyzed in HEK293 cells stably transfected with the mouse carriers mOct1, mOct2, mMate1, and mMate2, respectively. Results: Mouse mOct1, mOct2, and mMate1 showed significant TCl transport with Km values of 58.7, 78.5, and 29.3 µM, respectively. In contrast, mMate2 did not transport TCl but showed MPP<sup>+</sup> transport with Km of 60.0 µM that was inhibited by the drugs topotecan, acyclovir, and levofloxacin. Conclusion: TCl transport behavior as well as expression pattern were quite similar for the mouse carriers mOct1, mOct2, and mMate1 compared to their human counterparts. |
| first_indexed | 2024-03-10T13:52:39Z |
| format | Article |
| id | doaj.art-c9b1f38376654357b30704d02682f30a |
| institution | Directory Open Access Journal |
| issn | 1661-6596 1422-0067 |
| language | English |
| last_indexed | 2024-03-10T13:52:39Z |
| publishDate | 2020-12-01 |
| publisher | MDPI AG |
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| series | International Journal of Molecular Sciences |
| spelling | doaj.art-c9b1f38376654357b30704d02682f30a2023-11-21T02:02:09ZengMDPI AGInternational Journal of Molecular Sciences1661-65961422-00672020-12-012212210.3390/ijms22010022Trospium Chloride Transport by Mouse Drug Carriers of the Slc22 and Slc47 FamiliesMatthias Gorecki0Simon F. Müller1Regina Leidolf2Joachim Geyer3Institute of Pharmacology and Toxicology, Faculty of Veterinary Medicine, Justus Liebig University Giessen, 35392 Giessen, GermanyInstitute of Pharmacology and Toxicology, Faculty of Veterinary Medicine, Justus Liebig University Giessen, 35392 Giessen, GermanyInstitute of Pharmacology and Toxicology, Faculty of Veterinary Medicine, Justus Liebig University Giessen, 35392 Giessen, GermanyInstitute of Pharmacology and Toxicology, Faculty of Veterinary Medicine, Justus Liebig University Giessen, 35392 Giessen, GermanyBackground: The muscarinic receptor antagonist trospium chloride (TCl) is used for pharmacotherapy of the overactive bladder syndrome. TCl is a hydrophilic positively charged drug. Therefore, it has low permeability through biomembranes and requires drug transporters for distribution and excretion. In humans, the organic cation transporters OCT1 and OCT2 and the multidrug and toxin extrusion MATE1 and MATE2-K carriers showed TCl transport. However, their individual role for distribution and excretion of TCl is unclear. Knockout mouse models lacking mOct1/mOct2 or mMate1 might help to clarify their role for the overall pharmacokinetics of TCl. Method: In preparation of such experiments, TCl transport was analyzed in HEK293 cells stably transfected with the mouse carriers mOct1, mOct2, mMate1, and mMate2, respectively. Results: Mouse mOct1, mOct2, and mMate1 showed significant TCl transport with Km values of 58.7, 78.5, and 29.3 µM, respectively. In contrast, mMate2 did not transport TCl but showed MPP<sup>+</sup> transport with Km of 60.0 µM that was inhibited by the drugs topotecan, acyclovir, and levofloxacin. Conclusion: TCl transport behavior as well as expression pattern were quite similar for the mouse carriers mOct1, mOct2, and mMate1 compared to their human counterparts.https://www.mdpi.com/1422-0067/22/1/22trospiumtransportOCTMATEdrug excretiondrug transport |
| spellingShingle | Matthias Gorecki Simon F. Müller Regina Leidolf Joachim Geyer Trospium Chloride Transport by Mouse Drug Carriers of the Slc22 and Slc47 Families International Journal of Molecular Sciences trospium transport OCT MATE drug excretion drug transport |
| title | Trospium Chloride Transport by Mouse Drug Carriers of the Slc22 and Slc47 Families |
| title_full | Trospium Chloride Transport by Mouse Drug Carriers of the Slc22 and Slc47 Families |
| title_fullStr | Trospium Chloride Transport by Mouse Drug Carriers of the Slc22 and Slc47 Families |
| title_full_unstemmed | Trospium Chloride Transport by Mouse Drug Carriers of the Slc22 and Slc47 Families |
| title_short | Trospium Chloride Transport by Mouse Drug Carriers of the Slc22 and Slc47 Families |
| title_sort | trospium chloride transport by mouse drug carriers of the slc22 and slc47 families |
| topic | trospium transport OCT MATE drug excretion drug transport |
| url | https://www.mdpi.com/1422-0067/22/1/22 |
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