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Molecular Pharmacology, Vol 19, 92-96, Copyright © 1981 by the American Society for Pharmacology and Experimental Therapeutics

Carrier Mechanism and Specificity Accounting for the Increase in Intracellular Melphalan by the Basic Amino Acids

DAVID T. VISTICA 1 and BARBARA P. SCHUETTE 1

1 Laboratory of Medicinal Chemistry and Biology, National Cancer Institute, Bethesda, Maryland 20205

The basic amino acids arginine and its lower homologue, agr-amino-ggr-guanidinobutyric acid, increased the intracellular levels of melphalan only in the presence of leucine and sodium ions. This increase occurred solely through the monovalent cation-dependent, high-affinity, leucine-preferring transport system, one of the two amino acid transport systems responsible for melphalan uptake. Acceleration of melphalan exodus by leucine is antagonized by agr-amino-ggr-guanidinobutyric acid, resulting in increased cellular retention of melphalan.

Submitted on January 22, 1980
Accepted on August 4, 1980






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