Intestinal Breast Cancer Resistance Protein (BCRP)/Bcrp1 and Multidrug Resistance Protein 3 (MRP3)/Mrp3 Are Involved in the Pharmacokinetics of Resveratrol□S

The phytoestrogen resveratrol has putative health-promoting effects and is present in several dietary constituents. Resvera-trol is metabolized extensively in the gut epithelium, resulting in the formation of hydrophilic glucuronic acid and sulfate conju-gates. These polar resveratrol conjugates need specific trans-porters to cross the cell membrane. We show here that vecto-rial transport of some of these metabolites is mediated by multidrug resistance protein 3 (MRP3, ABCC3) and/or breast cancer resistance protein (BCRP, ABCG2) located in the baso-lateral and apical membranes of enterocytes, respectively. In vitro, MRP3 transports resveratrol-glucuronide (Res-3-G). The absence of Mrp3 in mice results in altered disposition of Res-3-G and its parent compound resveratrol, leading to a reduced percentage of resveratrol being excreted via the urine i