title: Contribution of radixin to P-glycoprotein expression and transport activity in mouse small intestine in vivo.
abstract: The ERM proteins, ezrin, radixin, and moesin, are membrane-cytoskeleton cross-linkers with multiple physiological functions. We previously showed that radixin is involved in posttranslational regulation of P-glycoprotein (P-gp) in human hepatoblastoma HepG2 cells. Here, we investigated the physiological role of radixin in regulating P-gp expression and activity in the small intestine by comparing wild-type- and radixin knockout (Rdx) mice. In intestinal tissue homogenates, P-gp protein levels increased markedly from the upper part to the lower part of the small intestine in both wild-type- and Rdx(-/-) mice. In the membrane fractions, a similar pattern was seen in wild-type mice. However, the membrane expression of P-gp protein remained at the same level from the upper to the lower part of the small intestine in Rdx(-/-) mice. When rhodamine123 (Rho123), a substrate of P-gp, was orally administered to Rdx(-/-) and wild-type mice, the absorption phase of Rho123 was greater in Rdx(-/-) than in wild-type mice, whereas the elimination phase in Rdx(-/-) mice was not different from that of wild-type mice. Our results indicate that radixin plays an important role in regulating P-gp localization and P-gp functional activity at the intestinal membrane.
authors.affiliation: Faculty of Pharmacy, Takasaki University of Health and Welfare, Takasaki, Gunma 370-0033, Japan.
authors.forename: Kentaro
authors.initials: K
authors.lastname: Yano
authors.forename: Takumi
authors.initials: T
authors.lastname: Tomono
authors.forename: Riyo
authors.initials: R
authors.lastname: Sakai
authors.forename: Takashi
authors.initials: T
authors.lastname: Kano
authors.forename: Kaori
authors.initials: K
authors.lastname: Morimoto
authors.forename: Yukio
authors.initials: Y
authors.lastname: Kato
authors.forename: Takuo
authors.initials: T
authors.lastname: Ogihara
mesh_terms: D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1 / Q000032:analysis / Q000235:genetics / Q000378:metabolism*; D000818:Animals; D003598:Cytoskeletal Proteins / Q000235:genetics / Q000378:metabolism*; D005786:Gene Expression Regulation; D007421:Intestine, Small / Q000378:metabolism*; D008297:Male; D008565:Membrane Proteins / Q000235:genetics / Q000378:metabolism*; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D012333:RNA, Messenger / Q000235:genetics; D020112:Rhodamine 123 / Q000008:administration & dosage / Q000097:blood / Q000378:metabolism
chemical_list: D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1; D003598:Cytoskeletal Proteins; D008565:Membrane Proteins; D012333:RNA, Messenger; C071776:radixin; D020112:Rhodamine 123
keywords: Absorption; ERM proteins; Efflux pumps; Intestinal secretion/transport; P-glycoprotein; Pharmacokinetics; in vivo; knockout mice; radixin