Antifolate transport in L1210 leukemia cells. Kinetic evidence for the non-identity of carriers for influx and efflux |
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Authors: | Micah Dembo Francis M Sirotnak |
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Institution: | Memorial Sloan-Kettering Cancer Center, New York, N.Y. 10021 U.S.A. |
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Abstract: | The kinetics of methotrexate transport in L1210 cells are described. Data derived from the measurements of initial influx, the complete time-course of uptake, intracellular steady-state level and unidirectional efflux were found to be consistent with a simple empirical equation containing three constants. Properties of the system include the following: (1) saturability of initial influx; (2) approach to steady state during uptake is expoential; (3) the half-time for drug uptake is independent of external concentration and qual to half-time for efflux; and (4) transport is concentrative at low external concentrations, whereas the reverse is true at high external concentrations. These observations are incorporated into a kinetic model which quantitatively accounts for the data on the basis of the hypothesis that influx and efflux take place via different carriers. |
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