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Kinetics of cellular permeability of phenoxazine and its dependence on P‐glycoprotein expression
Author(s) -
Wadkins Randy M.,
Houghton Peter J.
Publication year - 1993
Publication title -
febs letters
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.593
H-Index - 257
eISSN - 1873-3468
pISSN - 0014-5793
DOI - 10.1016/0014-5793(93)81098-k
Subject(s) - phenoxazine , kinetics , chemistry , p glycoprotein , efflux , biophysics , permeability (electromagnetism) , reaction rate constant , verapamil , enzyme kinetics , membrane , membrane transport , cell culture , biochemistry , multiple drug resistance , enzyme , biology , pharmacology , physics , calcium , antibiotics , genetics , organic chemistry , quantum mechanics , phenothiazine , active site
We present here the initial characterization of the mechanism of reversal of cellular resistance to Vinca alkaloids by phenoxazine (PZ). Changes in fluorescence upon cellular accumulation of PZ allowed measurement of the membrane transport kinetics in a sensitive KB‐3‐1 cell line and two multi‐drug resistant (MDR) counterparts. The accumulation of PZ is characterized by two uptake routes, with pseudo‐first order rate constants of 0.3 s −1 and 0.07 s −1 , while efflux of PZ from cells revealed rate constants of 0.2 s −1 . PZ rapidly reaches steady‐state concentrations within cells, which may make it more clinically useful than modulators that accumulate more slowly (e.g. verapamil).