Constitutive and Pregnane X Receptor: Regulators of Cytochrome P450 Induction
Nuclear Receptor Roles
Nuclear receptors, including the constitutive androstane receptor (CAR) and pregnane X receptor (PXR), play a crucial role in regulating the expression of genes encoding cytochrome P450 (CYP) enzymes. These receptors are activated by various xenobiotics and drugs, leading to the induction of CYP enzymes involved in drug and xenobiotic metabolism.CAR and PXR Function
CAR, encoded by the NR1I3 gene, is primarily expressed in the liver and protects it from injury. PXR, encoded by the NR1I2 gene, regulates the transcription of drug metabolizing enzymes and transporters.
CYP Regulation
CAR and PXR regulate the expression of specific CYP enzymes. CAR modulates CYP2B, while PXR controls CYP3A. These enzymes are responsible for metabolizing a wide range of drugs and foreign compounds.
Xenobiotic Response
CAR and PXR act as xenobiotic receptors, coordinating the body's response to foreign substances. They induce CYP enzymes to detoxify and eliminate environmental pollutants and toxicants.
Therapeutic Applications
Understanding the role of CAR and PXR in CYP regulation has therapeutic implications. It can help optimize drug metabolism and reduce adverse effects in patients receiving medications.
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