Mirogabalin, a novel α2δ ligand, is not a substrate of LAT1, but of PEPT1, PEPT2, OAT1, OAT3, OCT2, MATE1 and MATE2-K
Mirogabalin is a α2δ ligand as well as pregabalin. The aim of this study was to clarify whether mirogabalin is a substrate of human LAT1, which involved in absorption and disposition of pregabalin, and to investigate transporters involved in renal secretion and absorption of mirogabalin using transporter-expressing cells and fresh human kidney slices.We employed uptake assay of [3H]mirogabalin by HEK293T or HEK293 cells transiently overexpress human OAT1, OAT3, OCT2, LAT1/4F2hc, LAT2/4F2hc, PEPT1, and PEPT2 proteins. Transport assay of MDCKII cells transiently overexpress OCT2/MATE1, and OCT2/MATE2-K proteins was conducted. Contribution of transporters to renal secretion was investigated by uptake assay using human kidney slices.Uptake clearances of [3H]mirogabalin by OAT1-, OAT3-, OCT2-, PEPT1-, and PEPT2-expressing cells were higher than that by vector cells, but by LAT1/4F2hc and LAT2/4F2hc-expressing cells were not. In transport assay using OCT2/MATE1 and OCT2/MATE2-K cells, [3H]mirogabalin showed directional transport from basolateral to apical side. Contribution of OAT1, OAT3, and OCT2 was observed by uptake of [3H]mirogabalin into the kidney slices.These results indicate that mirogabalin is not a substrate of LAT1, but of PEPT1 and PEPT2 involved in absorption and of OAT1, OAT3, OCT2, MATE1 and/or MATE2-K involved in its urinary secretion.
| Medienart: |
E-Artikel |
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| Erscheinungsjahr: |
2022 |
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| Erschienen: |
2022 |
| Enthalten in: |
Zur Gesamtaufnahme - volume:52 |
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| Enthalten in: |
Xenobiotica; the fate of foreign compounds in biological systems - 52(2022), 9-11 vom: 06. Sept., Seite 997-1009 |
| Sprache: |
Englisch |
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| Beteiligte Personen: |
Yamamura, Naotoshi [VerfasserIn] |
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| Links: |
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| Anmerkungen: |
Date Completed 25.01.2023 Date Revised 01.02.2023 published: Print-Electronic Citation Status MEDLINE |
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| doi: |
10.1080/00498254.2022.2129517 |
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| funding: |
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| Förderinstitution / Projekttitel: |
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| PPN (Katalog-ID): |
NLM346856353 |
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| 100 | 1 | |a Yamamura, Naotoshi |e verfasserin |4 aut | |
| 245 | 1 | 0 | |a Mirogabalin, a novel α2δ ligand, is not a substrate of LAT1, but of PEPT1, PEPT2, OAT1, OAT3, OCT2, MATE1 and MATE2-K |
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| 500 | |a Date Completed 25.01.2023 | ||
| 500 | |a Date Revised 01.02.2023 | ||
| 500 | |a published: Print-Electronic | ||
| 500 | |a Citation Status MEDLINE | ||
| 520 | |a Mirogabalin is a α2δ ligand as well as pregabalin. The aim of this study was to clarify whether mirogabalin is a substrate of human LAT1, which involved in absorption and disposition of pregabalin, and to investigate transporters involved in renal secretion and absorption of mirogabalin using transporter-expressing cells and fresh human kidney slices.We employed uptake assay of [3H]mirogabalin by HEK293T or HEK293 cells transiently overexpress human OAT1, OAT3, OCT2, LAT1/4F2hc, LAT2/4F2hc, PEPT1, and PEPT2 proteins. Transport assay of MDCKII cells transiently overexpress OCT2/MATE1, and OCT2/MATE2-K proteins was conducted. Contribution of transporters to renal secretion was investigated by uptake assay using human kidney slices.Uptake clearances of [3H]mirogabalin by OAT1-, OAT3-, OCT2-, PEPT1-, and PEPT2-expressing cells were higher than that by vector cells, but by LAT1/4F2hc and LAT2/4F2hc-expressing cells were not. In transport assay using OCT2/MATE1 and OCT2/MATE2-K cells, [3H]mirogabalin showed directional transport from basolateral to apical side. Contribution of OAT1, OAT3, and OCT2 was observed by uptake of [3H]mirogabalin into the kidney slices.These results indicate that mirogabalin is not a substrate of LAT1, but of PEPT1 and PEPT2 involved in absorption and of OAT1, OAT3, OCT2, MATE1 and/or MATE2-K involved in its urinary secretion | ||
| 650 | 4 | |a Journal Article | |
| 650 | 4 | |a Mirogabalin | |
| 650 | 4 | |a active secretion | |
| 650 | 4 | |a human | |
| 650 | 4 | |a multidrug and toxin extrusion protein | |
| 650 | 4 | |a organic anion transporter | |
| 650 | 4 | |a organic cation transporter | |
| 650 | 4 | |a urinary excretion | |
| 650 | 7 | |a Organic Cation Transport Proteins |2 NLM | |
| 650 | 7 | |a mirogabalin |2 NLM | |
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| 650 | 7 | |a 55JG375S6M |2 NLM | |
| 650 | 7 | |a Organic Cation Transporter 2 |2 NLM | |
| 700 | 1 | |a Mikkaichi, Tsuyoshi |e verfasserin |4 aut | |
| 700 | 1 | |a Itokawa, Ken-Ichi |e verfasserin |4 aut | |
| 700 | 1 | |a Hoshi, Misa |e verfasserin |4 aut | |
| 700 | 1 | |a Damme, Katja |e verfasserin |4 aut | |
| 700 | 1 | |a Geigner, Stefanie |e verfasserin |4 aut | |
| 700 | 1 | |a Baumhauer, Christine |e verfasserin |4 aut | |
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