Localization and function of the organic anion-transporting polypeptide Oatp2 in rat liver.
OBJECTIVE
Multispecific organic anion-transporting polypeptides (Oatps) are involved in the transcellular movement of amphipathic compounds in many tissues including the liver, kidney, and blood-brain barrier. Recently, a high-affinity digoxin transporter (Oatp2) was cloned from rat brain and shown to be also expressed in the liver.


METHODS
We investigated the cellular and subcellular distribution of Oatp2 in rat liver by in situ hybridization technology and immunofluorescence microscopy and compared its substrate specificity with that of Oatp1 in complementary RNA-injected Xenopus laevis oocytes.


RESULTS
The results show a selective basolateral (sinusoidal) expression of Oatp2 in midzonal to perivenous hepatocytes, but not in periportal or the innermost layer of perivenous hepatocytes. Common substrates of both Oatp1 and Oatp2 include bile salts, steroid conjugates, thyroid hormones (T3, T4), ouabain, and the endothelin receptor antagonist BQ-123 (Michaelis constants: Oatp1, approximately 600 micromol/L; Oatp2, approximately 30 micromol/L). Other organic anions including sulfolithotaurocholate, bilirubin monoglucuronide, and sulfobromophthalein were transported only by Oatp1.


CONCLUSIONS
These results provide definite evidence for the partially overlapping and partially selective substrate specificities of Oatp1 and Oatp2. The unique acinar distribution of Oatp2 might indicate that it represents a high-affinity "backup" system for complete hepatocellular removal of certain cholephilic substances from portal blood plasma.
Reichel
C
C
Division of Clinical Pharmacology and Toxicology, Department of Internal Medicine, University Hospital, Zürich, Switzerland.
Gao
B
B
Van Montfoort
J
J
Cattori
V
V
Rahner
C
C
Hagenbuch
B
B
Stieger
B
B
Kamisako
T
T
Meier
P J
PJ
D000818:Animals; D027321:Anion Transport Proteins; D015153:Blotting, Western; D002352:Carrier Proteins / Q000235:genetics / Q000378:metabolism*; D017403:In Situ Hybridization; D008099:Liver / Q000378:metabolism* / Q000473:pathology; D008297:Male; D008856:Microscopy, Fluorescence; D012333:RNA, Messenger; D051381:Rats; D017207:Rats, Sprague-Dawley; D013379:Substrate Specificity; D014981:Xenopus
D027321:Anion Transport Proteins; D002352:Carrier Proteins; D012333:RNA, Messenger