title: Nucleoside transport in L1210 murine leukemia cells. Evidence for three transporters.
abstract: L1210 murine leukemia cells have two nucleoside transport activities that differ in their sensitivity to nitrobenzylmercaptopurine riboside (NBMPR). This study re-examines NBMPR-insensitive nucleoside transport in these cells and finds that it is mediated by two components, one Na(+)-dependent and the other Na(+)-independent. A mutant selected previously for loss of NBMPR-insensitive transport lacks only the Na(+)-independent activity. When NBMPR is used to block efflux via the NBMPR-sensitive transporter, uptake of formycin B (a nonmetabolized analog of inosine) is concentrative in both the parental and mutant cells, but the intracellular concentration of the nucleoside is 5-fold lower in the parental cells. Decreased accumulation of formycin B in the parental cells is due to efflux of the nucleoside via the NBMPR-insensitive, Na(+)-independent transporter that the mutant lacks. The Na(+)-dependent transporter appears to accept most purine, but not pyrimidine, nucleosides as substrates. Two exceptions are uridine, a good substrate, and 7-deazaadenosine, a poor substrate. In contrast, all of the nucleosides tested are substrates for the Na(+)-independent transporter. We conclude that L1210 cells have three distinct nucleoside transporters and that the specificity of the Na(+)-dependent transporter is similar to that of one of the two Na(+)-dependent nucleoside transporters seen in mouse intestinal epithelial cells.
authors.affiliation: Department of Biochemical and Clinical Pharmacology, St. Jude Children's Research Hospital, Memphis, Tennessee 38101.
authors.forename: C R
authors.initials: CR
authors.lastname: Crawford
authors.forename: C Y
authors.initials: CY
authors.lastname: Ng
authors.forename: L D
authors.initials: LD
authors.lastname: Noel
authors.forename: J A
authors.initials: JA
authors.lastname: Belt
mesh_terms: D000345:Affinity Labels / Q000494:pharmacology; D000818:Animals; D000903:Antibiotics, Antineoplastic / Q000378:metabolism*; D001692:Biological Transport / Q000187:drug effects; D005573:Formycins / Q000378:metabolism*; D007288:Inosine / Q000031:analogs & derivatives*; D007700:Kinetics; D007939:Leukemia L1210 / Q000378:metabolism*; D051379:Mice; D009705:Nucleosides / Q000378:metabolism*; D013868:Thioinosine / Q000031:analogs & derivatives* / Q000494:pharmacology
chemical_list: D000345:Affinity Labels; D000903:Antibiotics, Antineoplastic; D005573:Formycins; D009705:Nucleosides; C034561:formycin B; D013868:Thioinosine; D007288:Inosine; C001789:4-nitrobenzylthioinosine