|
Hokkaido University Collection of Scholarly and Academic Papers >
Faculty of Pharmaceutical Sciences >
Peer-reviewed Journal Articles, etc >
Uptake of antiepileptic drugs in forskolin-induced differentiated BeWo cells: alteration of gabapentin transport
| Title: | Uptake of antiepileptic drugs in forskolin-induced differentiated BeWo cells: alteration of gabapentin transport |
| Authors: | Koishikawa, Mai Browse this author | | Furugen, Ayako Browse this author →KAKEN DB | | Ohyama, Nanami Browse this author | | Narumi, Katsuya Browse this author →KAKEN DB | | Ishikawa, Shuhei Browse this author →KAKEN DB | | Kobayashi, Masaki Browse this author →KAKEN DB |
| Keywords: | BeWo | | placenta | | trophoblast | | differentiation | | antiepileptic drug | | gabapentin | | transporter |
| Issue Date: | 16-Jun-2022 |
| Publisher: | Taylor & Francis |
| Journal Title: | Xenobiotica |
| Volume: | 52 |
| Issue: | 4 |
| Start Page: | 405 |
| End Page: | 412 |
| Publisher DOI: | 10.1080/00498254.2022.2085635 |
| Abstract: | Previous studies have indicated that the expression levels of several transporters are altered during placental trophoblast differentiation. However, changes in the transport activities of therapeutic agents during differentiation must be comprehensively characterised. Antiepileptic drugs, including gabapentin (GBP), lamotrigine (LTG), topiramate, and levetiracetam, are increasingly prescribed during pregnancy. The objective of this study was to elucidate differences in the uptake of antiepileptic drugs during the differentiation process. Human placental choriocarcinoma BeWo cells were used as trophoblast models. For differentiation into syncytiotrophoblast-like cells, cells were treated with forskolin. The uptake of GBP and LTG was lower in differentiated BeWo cells than in undifferentiated cells. In particular, the maximum uptake rate of GBP transport was decreased in differentiated BeWo cells. Furthermore, GBP transport was trans-stimulated by the amino acids His and Met. We investigated the profiles of amino acids in undifferentiated and differentiated BeWo cells. Supplementation with His and Met, which demonstrated trans-stimulatory effects on GBP uptake, restored GBP uptake in differentiated cells. The findings of this study suggest that drug transport in BeWo cells can be altered before and after differentiation, and that the altered GBP uptake could be mediated by the intracellular amino acid status. |
| Rights: | This is an Accepted Manuscript of an article published by Taylor & Francis in Xenobiotica on 16th Jun 2022, available online: http://www.tandfonline.com/10.1080/00498254.2022.2085635. |
| Type: | article (author version) |
| URI: | http://hdl.handle.net/2115/89953 |
| Appears in Collections: | 薬学研究院 (Faculty of Pharmaceutical Sciences) > 雑誌発表論文等 (Peer-reviewed Journal Articles, etc)
|
Submitter: 古堅 彩子
|
