Cytotoxicity as an indicator for transport mechanism: evidence that melphalan is transported by two leucine-preferring carrier systems in the L1210 murine leukemia cell.
Melaphan, L-phenylalanine mustard, is transported by the L1210 cell through carriers of the leucine (L) type. Its initial rate of transport is inhibited by both L-leucine, a naturally occuring L system amino acid and 2-aminobicyclo[2,2,1]heptane-2-carboxylic acid (BCH), A SYNTHETIC AMINO ACID WHICH IS TRANSPORTED BY THE L system in the Ehrlich ascites tumor cell. Both amino acids inhibited melphalan transport comparably in sodium-free medium. However, BCH, in medium containing sodium, was unable to reduce a component of melphalan transport which was readily inhibited by leucine but not by alpha-aminoisobutyric acid. Inhibition analysis indicated that leucine competes with BCH for transport but that a portion of leucine transport is not readily inhibited by BCH. These results suggest that in the L1010 cell melphalan is transported equally by a BCH-sensitive, sodium-independent L system and a BCH-insensitive, sodium-dependent L system.
D000596:Amino Acids / Q000494:pharmacology; D000818:Animals; D001693:Biological Transport, Active / Q000187:drug effects; D001643:Bridged Bicyclo Compounds / Q000494:pharmacology; D002470:Cell Survival / Q000187:drug effects*; D002478:Cells, Cultured; D007930:Leucine / Q000378:metabolism* / Q000494:pharmacology; D007939:Leukemia L1210 / Q000188:drug therapy / Q000378:metabolism*; D008558:Melphalan / Q000378:metabolism* / Q000494:pharmacology
D000596:Amino Acids; D001643:Bridged Bicyclo Compounds; D007930:Leucine; D008558:Melphalan