Effects of Progesterone and Norethisterone on Cephalexin Transport and Peptide Transporter PEPT1 Expression in Human Intestinal Cell Line Caco-2(Pharmacology)

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We investigated the effects of progesterone and norethisterone on the apical-to-basolateral and basolateral-to-apical transports of cephalexin, a typical peptide transporter PEPT1 substrate, and the PEPT1 mRNA and protein expression levels, using the human intestinal cell line, Caco-2. Caco-2 cell monolayers (passages 50 to 60) were cultured on permeable membrane, plastic culture dish and culture tube. The Caco-2 cell monolayers were pretreated with progesterone and norethisterone (3, 10, 30μM) for 24h. After the pretreatment, the apical-to-ba-solateral and basolateral-to-apical transports of cephalexin were measured, and the densities of PEPT1 mRNA and protein expression levels were analyzed by reverse transcription-polymerase chain reaction (RT-PCR) and Western blot, respectively. The apical-to-basolateral transport of cephalexin was significantly decreased by the progesterone and norethisterone (30μM each) pretreatments. By contrast, the basolateral-to-apical transport of cephalexin was not altered by the same pretreatments. The densities of PEPT1 mRNA and protein expressions were significantly decreased by progesterone and norethisterone (each at 3 and 10μM) pretreatments compared with those of the non-treated Caco-2 cells. The results suggest that the transcription of the PEPT1 gene is down-regulated by the progesterone and norethisterone pretreatments. Further studies are needed to clarify whether the inhibition of the PEPT1 gene transcription by progesterone pretreatment proceeds via σ_1-receptor or progesterone receptor.
公益社団法人日本薬学会の論文
2006-01-01

Effects of Progesterone and Norethisterone on Cephalexin Transport and Peptide Transporter PEPT1 Expression in Human Intestinal Cell Line Caco-2(Pharmacology)

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