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Received for publication May 31, 2006.
Revised December 18, 2006.
Accepted for publication February 16, 2007.
Breast cancer resistance protein (Bcrp/Abcg2) is a member of the ATP-binding cassette transporter family with the ability to transport a variety of sulfate conjugates. In the present study, the regional expression and activity of Bcrp and SULTs were investigated in mouse intestine. Western blotting analysis revealed the highest expression of Bcrp in the ileum over the duodenum, jejunum and colon. Functional analysis of Bcrp was performed in everted intestinal sacs using 4-methylumbelliferone (4MU). The mucosal secretion clearance of 4MU sulfate formed in the enterocytes was markedly reduced in the jejunum, ileum and colon of Bcrp (-/-) mice in comparison with wild-type mice, while a slight and non-significant reduction was observed in the duodenum. The reduction in the mucosal secretion clearance was most marked in the ileum followed by the colon and jejunum. In addition, the mucosal secretion clearance of minoxidil sulfate, an active metabolite of minoxidil, was also significantly reduced in the intestine of Bcrp (-/-) mice. The sulfation activity of 4MU was higher in the colon than in the small intestine where glucuronidation activity was rather higher than the sulfation activity. Real-time PCR analysis showed that the expression of sulfotransferases, such as Sult1a1/2, Sult1b1 and Sult1d1, was also highest in the colon. These results suggest that Bcrp activity is higher in the mid- to lower intestine, and the cooperation of Bcrp and SULT provides an important detoxification pathway, particularly, in the colon.
Key words:
ABC transporters, intestinal transport, sulfate conjugation
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