TRANSPORT MECHANISM OF ANTHRACYCLINE DERIVATIVES IN RAT POLYMORPHONUCLEAR LEUKOCYTES - UPTAKE OF PIRARUBICIN, DAUNORUBICIN AND DOXORUBICIN

We performed experiments on the cis-inhibition and trans-stimulation e ffect on pirarubicin uptake in order to clarify the involvement of a c arrier in the pirarubicin, daunorubicin and/or doxorubicin transport s ystems in rat polymorphonuclear leukocytes. The uptake of daunorubicin and doxorubicin was a saturable concentration-dependent process. Sinc e the apparent kinetic constants, Michaelis constant (K-m) and inhibit ion constant (K-i), were almost comparable, these drugs presented mutu ally competitive inhibition. Furthermore, the pirarubicin uptake by po lymorphonuclear leukocytes was significantly elevated by increasing th e preloaded amount of doxorubicin, indicating that there was a trans-s timulation effect on the pirarubicin transport in the leukocytes. Thes e results suggest that carrier-mediated transport might be involved in the uptake of anthracycline derivatives, pirarubicin, daunorubicin an d doxorubicin, by rat polymorphonuclear leukocytes.