Drug transporters: Gatekeepers controlling access of xenobiotics to the cellular interior

Lesley A. Stanley; Brian C. Horsburgh; Jillian Ross; Nico Scheer; C. Roland Wolf

doi:10.1080/03602530802605040

Drug transporters: Gatekeepers controlling access of xenobiotics to the cellular interior

Lesley A. Stanley, Brian C. Horsburgh, Jillian Ross, Nico Scheer, C. Roland Wolf

Research output: Contribution to journal › Review article › peer-review

30 Citations (Scopus)

Abstract

In this paper, we evaluate methodologies and null mouse models used to study drug transporter function in vitro and in vivo. P-glycoprotein and MRP null mice have been used to examine many aspects of xenobiotic distribution and bioavailability. Their advantage over conventional models is that they allow the exclusion of transporters from a particular process; however, they cannot be used to study the activity of the transporter that has been deleted. Use of humanized mice permits a logical progression from phenomena in wild-type mice via the effects of removing the mouse transporter to the consequences of replacing it with its human counterpart.

Original language	English
Pages (from-to)	27-65
Number of pages	39
Journal	Drug Metabolism Reviews
Volume	41
Issue number	1
DOIs	https://doi.org/10.1080/03602530802605040
Publication status	Published - Feb 2009

Keywords

uptake
efflux
biological availability
genes, MDR
P-glycoprotein
multidrug resistance-associated protein 2
null mice
humanized mice
BLOOD-BRAIN-BARRIER
MDR1A P-GLYCOPROTEIN
MULTIDRUG-RESISTANCE PROTEIN
CENTRAL-NERVOUS-SYSTEM
ARTIFICIAL MEMBRANE-PERMEABILITY
DOUBLE KNOCKOUT MICE
ABSORPTION IN-VITRO
WILD-TYPE MICE
ORAL BIOAVAILABILITY
EFFLUX TRANSPORTERS

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title = "Drug transporters: Gatekeepers controlling access of xenobiotics to the cellular interior",

abstract = "In this paper, we evaluate methodologies and null mouse models used to study drug transporter function in vitro and in vivo. P-glycoprotein and MRP null mice have been used to examine many aspects of xenobiotic distribution and bioavailability. Their advantage over conventional models is that they allow the exclusion of transporters from a particular process; however, they cannot be used to study the activity of the transporter that has been deleted. Use of humanized mice permits a logical progression from phenomena in wild-type mice via the effects of removing the mouse transporter to the consequences of replacing it with its human counterpart.",

keywords = "uptake, efflux, biological availability, genes, MDR, P-glycoprotein, multidrug resistance-associated protein 2, null mice, humanized mice, BLOOD-BRAIN-BARRIER, MDR1A P-GLYCOPROTEIN, MULTIDRUG-RESISTANCE PROTEIN, CENTRAL-NERVOUS-SYSTEM, ARTIFICIAL MEMBRANE-PERMEABILITY, DOUBLE KNOCKOUT MICE, ABSORPTION IN-VITRO, WILD-TYPE MICE, ORAL BIOAVAILABILITY, EFFLUX TRANSPORTERS",

author = "Stanley, {Lesley A.} and Horsburgh, {Brian C.} and Jillian Ross and Nico Scheer and Wolf, {C. Roland}",

year = "2009",

month = feb,

doi = "10.1080/03602530802605040",

language = "English",

volume = "41",

pages = "27--65",

journal = "Drug Metabolism Reviews",

issn = "0360-2532",

publisher = "Taylor & Francis",

number = "1",

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TY - JOUR

T1 - Drug transporters: Gatekeepers controlling access of xenobiotics to the cellular interior

AU - Stanley, Lesley A.

AU - Horsburgh, Brian C.

AU - Ross, Jillian

AU - Scheer, Nico

AU - Wolf, C. Roland

PY - 2009/2

Y1 - 2009/2

N2 - In this paper, we evaluate methodologies and null mouse models used to study drug transporter function in vitro and in vivo. P-glycoprotein and MRP null mice have been used to examine many aspects of xenobiotic distribution and bioavailability. Their advantage over conventional models is that they allow the exclusion of transporters from a particular process; however, they cannot be used to study the activity of the transporter that has been deleted. Use of humanized mice permits a logical progression from phenomena in wild-type mice via the effects of removing the mouse transporter to the consequences of replacing it with its human counterpart.

AB - In this paper, we evaluate methodologies and null mouse models used to study drug transporter function in vitro and in vivo. P-glycoprotein and MRP null mice have been used to examine many aspects of xenobiotic distribution and bioavailability. Their advantage over conventional models is that they allow the exclusion of transporters from a particular process; however, they cannot be used to study the activity of the transporter that has been deleted. Use of humanized mice permits a logical progression from phenomena in wild-type mice via the effects of removing the mouse transporter to the consequences of replacing it with its human counterpart.

KW - uptake

KW - efflux

KW - biological availability

KW - genes, MDR

KW - P-glycoprotein

KW - multidrug resistance-associated protein 2

KW - null mice

KW - humanized mice

KW - BLOOD-BRAIN-BARRIER

KW - MDR1A P-GLYCOPROTEIN

KW - MULTIDRUG-RESISTANCE PROTEIN

KW - CENTRAL-NERVOUS-SYSTEM

KW - ARTIFICIAL MEMBRANE-PERMEABILITY

KW - DOUBLE KNOCKOUT MICE

KW - ABSORPTION IN-VITRO

KW - WILD-TYPE MICE

KW - ORAL BIOAVAILABILITY

KW - EFFLUX TRANSPORTERS

U2 - 10.1080/03602530802605040

DO - 10.1080/03602530802605040

M3 - Review article

SN - 0360-2532

VL - 41

SP - 27

EP - 65

JO - Drug Metabolism Reviews

JF - Drug Metabolism Reviews

IS - 1

ER -

Drug transporters: Gatekeepers controlling access of xenobiotics to the cellular interior

Abstract

Keywords

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