Transport of the immunosuppressant 15-deoxyspergualin in human peripheral blood lymphocytes.
15-deoxyspergualin (DSG) is a potent immunosuppressive compound currently in clinical trials. In this study, we have characterized the uptake and intracellular localization of DSG in human peripheral blood lymphocytes (PBL's). DSG is transported into human PBL's and reaches an estimated maximum concentration of approximately 500 microM in 6 hours. The majority of the [3H]-DSG remains in the cytoplasm of cells and that which is associated with the nucleus is only loosely associated. DSG was transported by HeLa cells, as well, suggesting uptake is not specific for hematopoietic cells. Positively charged amino acids and polyamines, which are structurally similar to DSG, were unable to compete for DSG transport suggesting that DSG is transported into cells via a pathway distinct from amino acids or polyamines.
Cleaveland
J S
JS
Bristol-Myers Squibb Pharmaceutical Research Institute, Seattle, Washington 98121.
Nadler
S G
SG
D001692:Biological Transport / Q000187:drug effects; D002467:Cell Nucleus / Q000378:metabolism; D002478:Cells, Cultured; D003600:Cytosol / Q000378:metabolism; D006146:Guanidines / Q000097:blood*; D006801:Humans; D007166:Immunosuppressive Agents / Q000097:blood*; D007700:Kinetics; D008214:Lymphocytes / Q000378:metabolism*; D011700:Putrescine / Q000494:pharmacology; D013095:Spermidine / Q000494:pharmacology; D013096:Spermine / Q000494:pharmacology; D013347:Subcellular Fractions / Q000378:metabolism; D014316:Tritium
D006146:Guanidines; D007166:Immunosuppressive Agents; D014316:Tritium; D013096:Spermine; D013095:Spermidine; C037258:gusperimus; D011700:Putrescine