TY - JOUR T1 - δ-Aminolevulinic Acid Transport in Cancer Cells of the Human Extrahepatic Biliary Duct JF - Journal of Pharmacology and Experimental Therapeutics JO - J Pharmacol Exp Ther SP - 219 LP - 224 DO - 10.1124/jpet.102.046573 VL - 305 IS - 1 AU - Jana Neumann AU - Matthias Brandsch Y1 - 2003/04/01 UR - http://jpet.aspetjournals.org/content/305/1/219.abstract N2 - This study was performed to characterize the transport of the endogenous photosensitizer δ-aminolevulinic acid in tumor cells of the extrahepatic biliary duct. Uptake of [3H]δ-aminolevulinic acid into human cholangiocarcinoma SK-ChA-1 cells was linear for up to 10 min, independent of a Na+ gradient, but stimulated 3- to 4-fold by an inwardly directed H+ gradient. Uptake of δ-aminolevulinic acid was mediated by a single transport system with an apparent affinity (Kt) of 2.1 mM and a maximal velocity (Vmax) of 60.1 nmol · 10 min−1 · mg of protein−1. Glycylsarcosine, alanylalanine, and cefadroxil strongly inhibited the [3H]δ-aminolevulinic acid uptake withKi values of 1.3, 0.2, and 3.6 mM, respectively. In contrast, γ-aminobutyric acid, glycine,l-glutamic acid, and l-aspartic acid (all 10 mM) had no effect on the total [3H]δ-aminolevulinic acid uptake, neither at pH 6.0 nor at pH 7.5. Applying a Dixon type of experiment and the ABC test revealed that glycylsarcosine and δ-aminolevulinic acid are transported via the same system, PEPT1. Treatment of the cells with phorbol 12-myristate 13-acetate, a phorbol ester that activates protein kinase C, resulted in a significant inhibition of the transport rate. This inhibition could be blocked by cotreatment with staurosporine. We conclude that δ-aminolevulinic acid is transported by the H+/peptide cotransporter PEPT1 into epithelial cells of the extrahepatic biliary duct. δ-Aminolevulinic acid can be accumulated specifically in bile duct tumor cells before photodynamic therapy. The American Society for Pharmacology and Experimental Therapeutics ER -