Kinetics of cellular permeability of phenoxazine and its dependence on P-glycoprotein expression

Randy M. Wadkins; Peter J. Houghton

doi:10.1016/0014-5793(93)81098-K

Kinetics of cellular permeability of phenoxazine and its dependence on P-glycoprotein expression

Randy M. Wadkins, Peter J. Houghton

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2 Citas (Scopus)

Resumen

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).

Idioma original	English (US)
Páginas (desde-hasta)	1-5
Número de páginas	5
Publicación	FEBS Letters
Volumen	322
N.º	1
DOI	https://doi.org/10.1016/0014-5793(93)81098-K
Estado	Published - may 3 1993
Publicado de forma externa	Sí

ASJC Scopus subject areas

Genetics
Molecular Biology
Biophysics
Structural Biology
Biochemistry
Cell Biology

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title = "Kinetics of cellular permeability of phenoxazine and its dependence on P-glycoprotein expression",

abstract = "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).",

keywords = "Modulator, Multi drug, Phenoxazine, Resistance, Vinca",

author = "Wadkins, {Randy M.} and Houghton, {Peter J.}",

note = "Funding Information: Acknowledgements: Supported by PHS awards CA23099 and CA21765fr om theN ationalC ancerI nstitutea ndA mericanL ebanese Syrian AssociatedC harities.",

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month = may,

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doi = "10.1016/0014-5793(93)81098-K",

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T1 - Kinetics of cellular permeability of phenoxazine and its dependence on P-glycoprotein expression

AU - Wadkins, Randy M.

AU - Houghton, Peter J.

N1 - Funding Information: Acknowledgements: Supported by PHS awards CA23099 and CA21765fr om theN ationalC ancerI nstitutea ndA mericanL ebanese Syrian AssociatedC harities.

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Y1 - 1993/5/3

N2 - 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).

AB - 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).

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KW - Multi drug

KW - Phenoxazine

KW - Resistance

KW - Vinca

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Kinetics of cellular permeability of phenoxazine and its dependence on P-glycoprotein expression

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