Related Experiment Video

Updated: Jun 17, 2026

A Simple and Efficient Method for In Vivo Cardiac-specific Gene Manipulation by Intramyocardial Injection in Mice
06:42

A Simple and Efficient Method for In Vivo Cardiac-specific Gene Manipulation by Intramyocardial Injection in Mice

Published on: April 16, 2018

Regulation of VDR expression in rat and human intestine and liver--consequences for CYP3A expression

Ansar A Khan1, Bieuwke S Dragt, Robert J Porte

  • 1Pharmacokinetics, Toxicology and Targeting, Department of Pharmacy, University of Groningen, Ant Deusinglaan 1, 9713 AV Groningen, The Netherlands. a.a.khan@rug.nl

Toxicology in Vitro : an International Journal Published in Association with BIBRA
|December 17, 2009
PubMed

Insights

Vitamin D receptor (VDR) expression in the liver is regulated by protein kinase C (PKC) and not by farnesoid X receptor (FXR) or VDR activation. Chenodeoxycholic acid (CDCA) may increase lithocholic acid (LCA) toxicity.

Area of Science:

  • Pharmacology
  • Hepatology
  • Gastroenterology

Background:

  • The vitamin D receptor (VDR) plays a crucial role in regulating drug-metabolizing enzymes and transporters in the liver and intestine.
  • However, the precise mechanisms controlling VDR expression in these organs remain incompletely understood.

Purpose of the Study:

  • To investigate the regulation of VDR mRNA expression in rat and human ileum and liver.
  • To examine the roles of VDR, farnesoid X receptor (FXR), glucocorticoid receptor (GR), and protein kinase C alpha (PKCalpha) ligands in VDR expression.

Main Methods:

  • Utilized precision-cut tissue slices from rat and human ileum and liver.
  • Administered various ligands including 1,25(OH)(2)D(3), chenodeoxycholic acid (CDCA), lithocholic acid (LCA), GW4064, phorbol-12-myristate-13-acetate (PMA), and specific inhibitors.

Main Results:

  • 1,25(OH)(2)D(3) induced VDR expression in rat ileum/liver and human ileum, but not human liver.
  • CDCA, but not LCA or GW4064, induced VDR mRNA in rat ileum and liver.
  • PKCalpha activation by PMA induced VDR in rat liver; PKCalpha inhibition blocked VDR induction by 1,25(OH)(2)D(3) and CDCA.
  • CDCA reduced VDR-mediated induction of CYP3A1 and CYP3A2 in rat ileum, despite increased VDR expression.

Conclusions:

  • VDR expression in rat liver appears to be regulated by PKC, independent of FXR or VDR activation.
  • CDCA may enhance LCA toxicity by inhibiting its metabolism, potentially through VDR-mediated pathways.

More Related Videos

An Intestine/Liver Microphysiological System for Drug Pharmacokinetic and Toxicological Assessment08:59

An Intestine/Liver Microphysiological System for Drug Pharmacokinetic and Toxicological Assessment

Published on: December 3, 2020

Establishment of Rat Models Mimicking Gender-affirming Hormone Therapies06:24

Establishment of Rat Models Mimicking Gender-affirming Hormone Therapies

Published on: January 10, 2025

Related Concept Videos

Pharmacogenetics of Phase I Enzymes: Cytochrome P450 Isozymes01:28

Pharmacogenetics of Phase I Enzymes: Cytochrome P450 Isozymes

Cytochrome P450 (CYP450) enzymes are a superfamily of heme-containing monooxygenases that play a pivotal role in Phase I drug metabolism by catalyzing oxidation and reduction reactions.These enzymes transform lipophilic xenobiotics into more hydrophilic metabolites, facilitating subsequent Phase II conjugation and eventual excretion. The CYP450 family is classified into families (e.g., CYP1–CYP3) and subfamilies (e.g., CYP2A, CYP2C), based on amino acid sequence homology.CYP450 isoenzymes,...
Cell Specific Gene Expression01:58

Cell Specific Gene Expression

Multicellular organisms contain a variety of structurally and functionally distinct cell types, but the DNA in all the cells originated from the same parent cells. The differences in the cells can be attributed to the differential gene expression. Liver cells, whose functions include detoxification of blood, production of bile to metabolize fats, and synthesis of proteins essential for metabolism, must express a specific set of genes to perform their functions. Gene expression also varies with...
Pharmacogenetics of Drug Metabolism: Overview01:27

Pharmacogenetics of Drug Metabolism: Overview

Genetic polymorphism in drug metabolism is crucial to the inter-individual variability observed in drug responses. Drug metabolism primarily involves the chemical modification of drugs and other xenobiotics to enhance their elimination by increasing their polarity. Two main classes of enzymes mediate this biotransformation process: Phase I enzymes, primarily cytochrome P450s, catalyze oxidation and reduction reactions, while other enzymes, such as esterases, mediate hydrolysis, and Phase II...
Transducer Mechanism: Nuclear Receptors01:31

Transducer Mechanism: Nuclear Receptors

Nuclear receptors, or NRs, are unique transcription factors that regulate gene transcription and affect the cellular pathways involved in reproduction, development, or metabolism. Their ability to be stimulated by small lipophilic ligands and control vital cellular processes makes them ideal drug targets. Nearly 10-15% of currently prescribed drugs target these receptors.
About 48 different soluble family members of nuclear receptors are identified that can be divided into two main classes:
Pharmacogenetic Phenotypes: Alterations in Pharmacokinetics, Drug Targets and Biologic Milieu01:29

Pharmacogenetic Phenotypes: Alterations in Pharmacokinetics, Drug Targets and Biologic Milieu

Genetic variations significantly influence drug response through pharmacokinetics, receptor interactions, and biologic milieu modifications. Pharmacokinetic alterations impact drug metabolism and clearance, affecting efficacy and toxicity. Variants in drug-metabolizing enzymes, such as CYP2C9 and CYP2C19, alter drug activation and elimination. For example, CYP2C9 loss-of-function variants require lower warfarin doses to prevent excessive bleeding, while CYP2C19 variants reduce clopidogrel...
Pharmacogenetics of Drug Targets: β₂-Adrenergic Receptors, Apo E, Thymidylate Synthase01:11

Pharmacogenetics of Drug Targets: β₂-Adrenergic Receptors, Apo E, Thymidylate Synthase

Genetic polymorphisms in drug targets have emerged as critical determinants of interindividual variability in drug response and toxicity. Pharmacogenomic investigations increasingly focus on identifying these variations to personalize and optimize therapeutic interventions. A drug target may be a receptor, enzyme, or signaling protein involved in pharmacologic responses or disease-related pathways. While early pharmacogenetic studies focused primarily on drug metabolism, current research...