Uptake of antiepileptic drugs in forskolin-induced differentiated BeWo cells: alteration of gabapentin transport

Koishikawa, Mai; Furugen, Ayako; Ohyama, Nanami; Narumi, Katsuya; Ishikawa, Shuhei; Kobayashi, Masaki

Uptake of antiepileptic drugs in forskolin-induced differentiated BeWo cells: alteration of gabapentin transport

Koishikawa, Mai; Furugen, Ayako; Ohyama, Nanami et al.

Xenobiotica, 2022, 52(4), 405-412

Permalink : https://hdl.handle.net/2115/89953

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アクセス権	open access
URI	https://hdl.handle.net/2115/89953
タイトル	Uptake of antiepileptic drugs in forskolin-induced differentiated BeWo cells: alteration of gabapentin transport
著者	Koishikawa, Mai ; Furugen, Ayako ; Ohyama, Nanami ; Narumi, Katsuya ; Ishikawa, Shuhei ; Kobayashi, Masaki
著者名 Koishikawa, Mai
e-Rad_Researcher 90767261 著者名 Furugen, Ayako
著者名 Ohyama, Nanami
e-Rad_Researcher 90746752 著者名 Narumi, Katsuya
e-Rad_Researcher 30880091 著者名 Ishikawa, Shuhei
e-Rad_Researcher 70431319 著者名 Kobayashi, Masaki
言語	英語
キーワード	BeWo
	placenta
	trophoblast
	differentiation
	antiepileptic drug
	gabapentin
	transporter
発行日	2022-06-16
出版者	Taylor & Francis
収録物名	Xenobiotica
巻(号)	52(4)
ページ	405-412
抄録	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.
資源タイプ	学術雑誌論文
出版タイプ	Accepted Manuscript
権利情報	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.
PISSN	0049-8254
関連情報 (isVersionOf)	出版社版DOI https://doi.org/10.1080/00498254.2022.2085635