Localization and function of the organic anion-transporting polypeptide Oatp2 in rat liver

Citation
C. Reichel et al., Localization and function of the organic anion-transporting polypeptide Oatp2 in rat liver, GASTROENTY, 117(3), 1999, pp. 688-695
Citations number
42
Language
INGLESE
art.tipo
Article
Categorie Soggetti
Gastroenerology and Hepatology","da verificare
Journal title
GASTROENTEROLOGY
ISSN journal
0016-5085 → ACNP
Volume
117
Issue
3
Year of publication
1999
Pages
688 - 695
Database
ISI
SICI code
0016-5085(199909)117:3<688:LAFOTO>2.0.ZU;2-F
Abstract
Background & Aims: Multispecific organic anion-transporting polypeptides (O atps) are involved in the transcellular movement of amphipathic compounds i n many tissues including the liver, kidney, and blood-brain barrier. Recent ly, a high-affinity digoxin transporter (Oatp2) was cloned from rat brain a nd shown to be also expressed in the liver. Methods: We investigated the ce llular and subcellular distribution of Oatp2 in rat liver by in situ hybrid ization technology and immunofluorescence microscopy and compared its subst rate specificity with that of Oatp1 in complementary RNA-injected Xenopus l aevis oocytes. Results, The results show a selective basolateral (sinusoida l) expression of Oatp2 in midzonal to perivenous hepatocytes, but not in pe riportal or the innermost layer of perivenous hepatocytes. Common substrate s of both Oatp1 and Oatp2 include bile salts, steroid conjugates, thyroid h ormones (T3, T4), ouabain, and the endothelin receptor antagonist BQ-123 (M ichaelis constants: Oatp1, similar to 600 mu mol/L; Oatp2, similar to 30 mu mol/L). Other organic anions including sulfolithotaurocholate, bilirubin m onoglucuronide, and sulfobromophthalein were transported only by Oatp1. Con clusions: These results provide definite evidence for the partially overlap ping and partially selective substrate specificities of Oatp1 and Oatp2. Th e unique acinar distribution of Oatp2 might indicate that it represents a h igh-affinity "backup'" system for complete hepatocellular removal of certai n cholephilic substances from portal blood plasma.