PT  - JOURNAL ARTICLE
AU  - Y Tomita
AU  - M Takano
AU  - M Yasuhara
AU  - R Hori
AU  - K Inui
TI  - Transport of oral cephalosporins by the H+/dipeptide cotransporter and distribution of the transport activity in isolated rabbit intestinal epithelial cells.
DP  - 1995 Jan 01
TA  - Journal of Pharmacology and Experimental Therapeutics
PG  - 63--69
VI  - 272
IP  - 1
4099  - http://jpet.aspetjournals.org/content/272/1/63.short
4100  - http://jpet.aspetjournals.org/content/272/1/63.full
SO  - J Pharmacol Exp Ther1995 Jan 01; 272
AB  - Transport of cephalosporins was studied using isolated rabbit intestinal epithelial cells. Cephradine uptake by the cells was concentrative and was inhibited by the addition of glycylsarcosine. The accumulated cephradine was effluxed from the cells by the addition of a protonophore, carbonyl cyanide 4-trifluoromethoxyphenylhydrazone (FCCP). Amiloride, an inhibitor of the Na+/H+ exchanger, reduced the steady-state uptake of cephradine, suggesting that the exchanger contributes to the maintenance of an inward H+ gradient as a driving force. Cephradine uptake by ATP-depleted intestinal cells was actively driven by the inward H+ gradient and was inhibited by FCCP and glycylsarcosine. The distribution of cephradine transport activity along the small intestine and villus-crypt axis was also examined in the isolated cells, and the transport activity was higher in the upper parts of the intestinal segments and in villus cells. These results indicate that the uptake of oral cephalosporins by intestinal epithelial cells in concentrative and reversible and that the H+/dipeptide cotransporter and the Na+/H+ exchanger play an important role for the active uptake of these drugs. The activity of the H+/dipeptide cotransporter should be higher in upper segments and in villus cells of the small intestine.