thesis

Cytochrome P450 3A and ABC-transport proteins in horse

Abstract

In this thesis cytochrome P450 3A (CYP3A) and the ABC-transport proteins P-glycoprotein (P-gp), breast cancer resistance protein (BCRP), multidrug resistance protein 1 (MRP1) and multidrug resistance protein 2 (MRP2) have been studied in horse. In the first part of the thesis the gene and protein expression, cellular localization and metabolic activity of CYP3A were investigated in the intestines, liver and upper respiratory airways. High levels of CYP3A gene and protein expression and metabolic activity were found in the small intestines. The CYP3A-related activity in the upper respiratory airways was high in spite of rather low levels of CYP3A gene and protein expression. A possible explanation in this observation is that there is an efficient electron transport from NADPH P450 reductase and cytochrome b5 to CYP3A in these tissues. In the second part of the thesis gene and protein expression and cellular localization of P-gp, BCRP, MRP1 and MRP2 were studied in the intestines, liver and kidney. The expression and localization of the transporters in the tissues of horse showed both similarities and differences compared to other species. Collectively the results of the present thesis indicate that CYP3A and the examined ABC-transport proteins have important roles for bioavalability and elimination of substrate compounds in horse

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