5-Aminolaevulinic acid methyl ester transport on amino acid carriers in a human colon adenocarcinoma cell line.
The transport mechanisms of 5-aminolevulinic acid methyl ester (5-ALA-ME) have been studied in a human adenocarcinoma cell line (WiDr) by means of 14[C]-labeled 5-ALA-ME. The transport was found to be partly Na+ dependent, while the extracellular Cl- concentration did not affect the uptake. The transport of 5-ALA-ME into WiDr cells was dependent on the incubation temperature and was found to be completely blocked by the inhibitors of energy metabolism, 2-deoxyglucose and sodium azide. WiDr cells were treated with 10 mM of 14 different amino acids and the substrate specificity of the 5-ALA-ME transporter(s) was analyzed by treating the cells with 23 microM or 1 mM 14[C]-labeled 5-ALA-ME. The transport of 5-ALA-ME was found to be inhibited to the highest extent, i.e. about 60%, by the nonpolar amino acids L-alanine, L-methionine, L-tryptophan and glycine. The uptake of 5-ALA-ME followed an exponential decay with increasing concentration of glycine, reaching a maximum inhibition of uptake of 5-ALA-ME of 55%. Sarcosine, a specific inhibitor of system Gly, did not significantly inhibit 5-ALA-ME transport. In contrast to transport of 5-ALA, 5-ALA-ME does not seem to be taken up by system BETA transporters. In conclusion, the cellular uptake of 5-ALA-ME into WiDr cells seems to be due to active transport mechanisms, involving transporters of nonpolar amino acids.
Gederaas
O A
OA
Institute of Laboratory Medicine, Department of Clinical Chemistry, Medical Faculty, Norwegain University of Science and Technology, Trondheim, Norway.
Holroyd
A
A
Brown
S B
SB
Vernon
D
D
Moan
J
J
Berg
K
K
D000230:Adenocarcinoma / Q000378:metabolism; D026905:Amino Acid Transport Systems; D000596:Amino Acids / Q000494:pharmacology; D000622:Aminolevulinic Acid / Q000031:analogs & derivatives* / Q000378:metabolism*; D000963:Antimetabolites / Q000494:pharmacology; D001693:Biological Transport, Active / Q000187:drug effects; D002352:Carrier Proteins / Q000378:metabolism; D003110:Colonic Neoplasms / Q000378:metabolism; D006801:Humans; D017319:Photosensitizing Agents / Q000378:metabolism*; D014407:Tumor Cells, Cultured
D026905:Amino Acid Transport Systems; D000596:Amino Acids; D000963:Antimetabolites; D002352:Carrier Proteins; D017319:Photosensitizing Agents; C114767:delta-aminolevulinic acid methyl ester; D000622:Aminolevulinic Acid