Transport and uptake of nateglinide in Caco-2 cells and its inhibitory effect on human monocarboxylate transporter MCT1

Atsuko Okamura, Akiko Emoto, Noriko Koyabu, Hisakazu Ohtani, Yasufumi Sawada

研究成果: Article査読

41 被引用数 (Scopus)

抄録

1 Nateglinide, a novel oral hypoglycemic agent, rapidly reaches the maximum serum concentration after oral administration, suggesting that it is rapidly absorbed in the gastrointestinal tract. The aim of this work is to clarify the intestinal absorption mechanism of nateglinide by means of in vitro studies. 2 We examined the transcellular transport and the apical uptake of [ 14C]nateglinide in a human colon carcinoma cell line (Caco-2). We also examined whether nateglinide is transported via monocarboxylate transport-1 (MCT1) by means of an uptake study using MCT1-expressing Xenopus laevis oocytes. 3 In Caco-2 cells, the transcellular transport of [ 14C]nateglinide from the apical to basolateral side was greater than that in the opposite direction. The uptake of [ 14C]nateglinide from the apical side was concentration-dependent, H +-dependent, and Na +-independent. Kinetic analysis revealed that the Kt and Jmax values of the initial uptake rate of [ 14C]nateglinide were 448 μM and 43.2 nmol mg protein -1 5 min -1, respectively. Various monocarboxylates, including salicylic acid and valproic acid, and glibenclamide significantly inhibited the uptake of [ 14C]nateglinide. 4 The uptake study using MCT1-expressing oocytes showed that nateglinide inhibits the MCT1-mediated uptake of [ 14C]L-lactic acid, though nateglinide itself is not transported by MCT1. 5 Taken together, these results suggest that the uptake of nateglinide from the apical membranes of Caco-2 cells is, at least in part, mediated by a proton-dependent transport system(s) distinct from MCT1.

本文言語English
ページ(範囲)391-399
ページ数9
ジャーナルBritish Journal of Pharmacology
137
3
DOI
出版ステータスPublished - 2002 10月
外部発表はい

ASJC Scopus subject areas

  • 薬理学

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