Dideoxycytidine permeation and salvage by mouse leukemia cells and human erythrocytes

Biochem Pharmacol. 1989 Oct 15;38(20):3469-75. doi: 10.1016/0006-2952(89)90116-0.

Abstract

Transmembrane equilibration of dideoxycytidine (ddCyd) in P388 mouse leukemia cells and human erythrocytes was only 1% as rapid as that of uridine and 2'-deoxycytidine which is mediated by the facilitated nucleoside transporter of these cells. ddCyd entry was nonsaturable up to a concentration of 1 mM but was partially inhibited by dipyridamole, nitrobenzylthioinosine and nucleosides, but not by nucleobases. Thus, entry was partly (70-80%) mediated, though very inefficiently, by the nucleoside carrier. Intracellular phosphorylation of ddCyd in P388 cells was also very inefficient compared to that of 2'-deoxycytidine and uridine and not rate limited by its slow entry into the cells.

Publication types

  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Animals
  • Blood Proteins / physiology
  • Carrier Proteins / physiology
  • Dipyridamole / pharmacology
  • Erythrocytes / metabolism*
  • Humans
  • Hydroxyurea / pharmacology
  • Leukemia, Experimental / metabolism*
  • Membrane Proteins / physiology
  • Mice
  • Nucleoside Transport Proteins
  • Permeability
  • Solubility
  • Structure-Activity Relationship
  • Thioinosine / pharmacology
  • Uridine / pharmacokinetics
  • Zalcitabine / pharmacokinetics*

Substances

  • Blood Proteins
  • Carrier Proteins
  • Membrane Proteins
  • Nucleoside Transport Proteins
  • Thioinosine
  • Dipyridamole
  • Zalcitabine
  • 4-nitrobenzylthioinosine
  • Uridine
  • Hydroxyurea