Expression of cytochrome P50s and transcription factors Pxr and Car in canine tissues

Abstract

Dogs are widely used in the pharmaceutical industry for many study types, including those that will impact decisions on drug development. The purpose of this study was to determine the expression of cytochrome P450 (CYP) genes in canine tissues using quantitative real-time polymerase chain reaction (qPCR). The CYPs that determined the expression in canine tissues were CYP1A2, CYP2A13, CYP2B11, CYP2C41, CYP2D15, CYP2E1, CYP3A12, CYP4A11, CYP4F3 and CYP19 (aromatase). We have also determined the expression of two transcription factors that regulate the expression of CYPs, the constitutive androstane receptor (CAR) and pregnane X receptor (PXR). Our results have shown that CYP1A2 was expressed in high levels in the lungs, CYP2A13 in the small intestine, the stomach, the kidney and the brain, CYP2B11 in liver, small intestine and kidney, CYP2C41 in liver and stomach, CYP2D15 in stomach, CYP2E1 in brain, small intestine and brain, CYP3A12 in many tissues, CYP4A11 in small intestine and CYP4F3 in brain and stomach. CYP19 was expressed in liver, stomach, uterus, small intestine, kidney and hypothalamus. PXR and CAR were expressed in many tissues. In conclusion, the existence of differences in the expression of CYPs, PXR and CAR in various tissues of a healthy dog may be associated with location-specific functions and provide useful information on drug metabolism in dogs. ©PHARMAKON-Press.