Active carrier-mediated transport of melphalan by two separate amino acid transport systems in LPC-1 plasmacytoma cells in vitro.
Previous studies have shown that uptake of several alkylating agents occurs by independent transport mechanisms. Uptake of one of these agents, the phenylalanine derivative of nitrogen mustard (melphalan), has been investigated in LPC-1 plasmacytoma cells in vitro. Evidence suggesting that melphalan uptake is an active process is that uptake of free intact melphalan proceeds "uphill" against a concentration gradient, is temperature- and sodium-dependent, and is inhibited by several metabolic antagonists. Other findings supporting the concept that melphalan uptake is carrier-mediated is that uptake follows biphasic Michaelis-Menten kinetics, is chemically specific, and is mediated by at least two separate amino acid transport systems. Uptake by one system was sensitive to DL-beta-2-aminobicyclo[2,2,1]-heptane-2-carboxylic acid, was sodium-independent, and appeared to be mediated by system L. The second unassigned system was characterized by sodium dependence, insensitivity to 2-aminoisobutyric acid and 2-(methylamino)isobutyric acid, and was inhibited by alanine, serine, cysteine, and other amino acids.
D000596:Amino Acids / Q000494:pharmacology; D001693:Biological Transport, Active / Q000187:drug effects; D002352:Carrier Proteins / Q000378:metabolism*; D002460:Cell Line; D005973:Glutamine / Q000378:metabolism*; D007700:Kinetics; D007930:Leucine / Q000378:metabolism*; D008558:Melphalan / Q000378:metabolism*
D000596:Amino Acids; D002352:Carrier Proteins; D005973:Glutamine; D007930:Leucine; D008558:Melphalan