IFISE 05411
INSTITUTO DE FISIOLOGIA EXPERIMENTAL
Unidad Ejecutora - UE
artículos
Título:
Hepatic drug transporters and nuclear receptors: Regulation
Autor/es:
MOTTINO, ALDO D; CATANIA, VIVIANA
Revista:
World journal of gastroenterology
Referencias:
Año: 2008 vol. 14 p. 7068 - 7074
Resumen:
The canalicular membrane represents the excretory pole
of hepatocytes. Bile is an important route of elimination
of potentially toxic endo- and xenobiotics (including
drugs and toxins), mediated by the major canalicular
transporters: multidrug resistance protein 1 (MDR1,
ABCB1), also known as P-glycoprotein, multidrug resistance-
associated protein 2 (MRP2, ABCC2), and the
breast cancer resistance protein (BCRP, ABCG2). Their
activities depend on regulation of expression and proper
localization at the canalicular membrane, as regulated
by transcriptional and post-transcriptional events, respectively.
At transcriptional level, specific nuclear receptors
(NR)s modulated by ligands, co-activators and
co-repressors, mediate the physiological requirements
of these transporters. This complex system is also responsible
for alterations occurring in specific liver pathologies.
We briefly describe the major Class U NRs,
pregnane X receptor (PXR) and constitutive androstane
receptor (CAR), and their role in regulating expression
of multidrug resistance proteins. Several therapeutic
agents regulate the expression of relevant drug transporters
through activation/inactivation of these NRs. We
provide some representative examples of the action of
therapeutic agents modulating liver drug transporters,
which in addition, involve CAR or PXR as mediators.
pregnane X receptor (PXR) and constitutive androstane
receptor (CAR), and their role in regulating expression
of multidrug resistance proteins. Several therapeutic
agents regulate the expression of relevant drug transporters
through activation/inactivation of these NRs. We
provide some representative examples of the action of
therapeutic agents modulating liver drug transporters,
which in addition, involve CAR or PXR as mediators.
We briefly describe the major Class U NRs,
pregnane X receptor (PXR) and constitutive androstane
receptor (CAR), and their role in regulating expression
of multidrug resistance proteins. Several therapeutic
agents regulate the expression of relevant drug transporters
through activation/inactivation of these NRs. We
provide some representative examples of the action of
therapeutic agents modulating liver drug transporters,
which in addition, involve CAR or PXR as mediators.
pregnane X receptor (PXR) and constitutive androstane
receptor (CAR), and their role in regulating expression
of multidrug resistance proteins. Several therapeutic
agents regulate the expression of relevant drug transporters
through activation/inactivation of these NRs. We
provide some representative examples of the action of
therapeutic agents modulating liver drug transporters,
which in addition, involve CAR or PXR as mediators.
thologies.
We briefly describe the major Class U NRs,
pregnane X receptor (PXR) and constitutive androstane
receptor (CAR), and their role in regulating expression
of multidrug resistance proteins. Several therapeutic
agents regulate the expression of relevant drug transporters
through activation/inactivation of these NRs. We
provide some representative examples of the action of
therapeutic agents modulating liver drug transporters,
which in addition, involve CAR or PXR as mediators.
pregnane X receptor (PXR) and constitutive androstane
receptor (CAR), and their role in regulating expression
of multidrug resistance proteins. Several therapeutic
agents regulate the expression of relevant drug transporters
through activation/inactivation of these NRs. We
provide some representative examples of the action of
therapeutic agents modulating liver drug transporters,
which in addition, involve CAR or PXR as mediators.
U NRs,
pregnane X receptor (PXR) and constitutive androstane
receptor (CAR), and their role in regulating expression
of multidrug resistance proteins. Several therapeutic
agents regulate the expression of relevant drug transporters
through activation/inactivation of these NRs. We
provide some representative examples of the action of
therapeutic agents modulating liver drug transporters,
which in addition, involve CAR or PXR as mediators.
