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Diurnal difference in CAR mRNA expression
Yuichiro Kanno1, Satoshi Otsuka, Takuya Hiromasa
1Faculty of Pharmaceutical Sciences, Toho University, 2-2-1 Miyama, Funabashi, Chiba 274-8510, Japan. yinouye@phar.toho-u.ac.jp
Nuclear Receptor
|August 31, 2004
Summary
The constitutive androstane receptor (CAR) mRNA expression follows a daily rhythm, peaking at night. This circadian pattern influences how the body processes drugs and foreign substances, impacting disease treatment.
Area of Science:
- Pharmacology
- Chronobiology
- Molecular Biology
Background:
- The constitutive androstane receptor (CAR, NR1I3) is crucial for activating genes involved in drug and xenobiotic metabolism.
- Understanding CAR's regulation is vital for drug development and personalized medicine.
Purpose of the Study:
- To investigate the circadian rhythm of CAR mRNA expression.
- To determine the relationship between CAR mRNA oscillation and its function in drug metabolism.
Main Methods:
- Quantitative real-time PCR was used to measure CAR mRNA levels over a 24-hour period.
- Expression levels were analyzed in relation to known circadian clock genes (Bmal1, Rev-erbalpha).
Main Results:
- CAR mRNA exhibits a distinct circadian rhythm, peaking at Zeitgeber time 20 and troughing at ZT8, with a 2.0-fold difference.
- CAR mRNA expression was found to be in phase with Bmal1 and in antiphase with Rev-erbalpha.
- Diurnal variations in CAR mRNA correlate with a 1.7-fold difference in PB-dependent CYP2B1/2 mRNA induction.
Conclusions:
- Circadian oscillation of the xenosensor gene CAR mRNA is demonstrated for the first time.
- This rhythmic expression partially explains chronopharmacokinetics and chronopharmacology in disease states.
- CAR's daily rhythm influences the body's response to xenobiotics, impacting drug efficacy and toxicity over time.