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.
Institute of Laboratory Medicine, Department of Clinical Chemistry, Medical Faculty, Norwegain University of Science and Technology, Trondheim, Norway.
O A
OA
Gederaas
A
A
Holroyd
S B
SB
Brown
D
D
Vernon
J
J
Moan
K
K
Berg
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