Expression, Activity and Regulation of CYP3A in Human and Rodent Brain

Abstract

The importance of cytochrome P450 (CYP) 3A enzymes in human drug metabolism is well established. The function of these enzymes has been characterized extensively in liver and intestinal tissues but much less is known about their expression, regulation and functional activity in the brain. Several lines of evidence point to the presence and function of multiple forms of CYP enzymes, including CYP3A, in both human and rodent brain. Expression studies suggest that CYP3A enzymes show regional differences in their distribution in the brain, where they may play a role in steroid metabolism. They also metabolize many psychoactive drugs and may have a profound effect on their efficacy and safety. This review explores the tissue, cellular, and subcellular expression of CYP3A isoforms in human and rodent brain and provides insight into their functional roles and regulation.

Key Words :

• CYP3A
• CYP3A4
• CYP3A5
• Cytochrome P450
• Brain
• Metabolism
• Biotransformation

Acknowledgments

This work was supported by grant #MOP-56976 from the Canadian Institutes of Health Research awarded to Dr. R. Bendayan. Dr. D. Fawcett was a Visiting Scientist in Dr. Bendayan's laboratory at the time this manuscript was prepared. The authors wish to thank Mr. Calvin H.F. Lau for his help in researching material for this manuscript and Ms. Monica Banach for her administrative assistance.