D-cycloserine uses an active transport mechanism in the human intestinal cell line Caco 2.

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RESUMO

In a previous study we have shown that cultured epithelial cell lines can be used to measure the transepithelial passage of antimicrobial agents across the intestine and to obtain information on the mechanisms of transport utilized and predict the bioavailability of the antimicrobial agents after oral administration. In particular, among the drugs investigated, D-cycloserine had been shown to be transported in a polarized manner only in the intestinal cells. In the present work, further characterization of the transport of D-cycloserine in the human intestinal cell line Caco 2 has shown that this occurs in the apical-to-basolateral direction by an active mechanism which is energy dependent but only partially sodium dependent. Competition studies have also indicated that the transport of D-cycloserine occurs via a carrier for imino acids, amino acids with aliphatic side chains (L-Ala, D-Ala, and beta Ala), and L-Trp, L-Tyr, L-Cys, and alpha-amino isobutyric acid. This system may correspond to a proton-dependent system for L-proline and beta-alanine recently described for Caco 2 cells. In contrast with the cephalosporins, which are taken up by the Caco 2 cells via a dipeptide carrier, D-cycloserine transport cannot be inhibited by either cephalexin (a member of the class of cephalosporins) or dipeptides.

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