Localization of organic anion transporting polypeptide 4 (Oatp4) in rat liver and comparison of its substrate specificity with Oatp1, Oatp2 and Oatp3.
Organic anion transporting polypeptides (rodents: Oatps; human: OATPs) are involved in the absorption and elimination of a wide variety of structurally unrelated amphipathic organic compounds. Several members of this protein family mediate the uptake of substrates across the basolateral membrane of hepatocytes as the first step in hepatic elimination. In contrast to the well-characterized Oatp1 and Oatp2, the localization and substrate specificity of the recently cloned Oatp4 have not been investigated in detail. Therefore, we raised an antibody against the C-terminal end of Oatp4 and localized this 85-kDa protein to the basolateral membrane of rat hepatocytes. Similar to Oatp1 and Oatp2, Oatp4 is a multispecific transporter with high affinities for bromosulfophthalein, dehydroepiandrosterone sulfate, leukotriene C4, and anionic peptides. In addition, we compared the substrate specificity of Oatp4 to that of Oatp3, which so far has mainly been shown to mediate intestinal bile acid transport. Oatp3 had a similar broad substrate specificity, but in general much lower affinities than Oatp4. Thus, while Oatp4 seems to work in concert with Oatp1 and Oatp2 in the basolateral membrane of rat hepatocytes, Oatp3 is a multispecific transport system in the small intestine.
Cattori
V
V
Division of Clinical Pharmacology and Toxicology, Department of Internal Medicine, University Hospital, 8091 Zurich, Switzerland.
van Montfoort
J E
JE
Stieger
B
B
Landmann
L
L
Meijer
D K
DK
Winterhalter
K H
KH
Meier
P J
PJ
Hagenbuch
B
B
D000818:Animals; D001692:Biological Transport; D005260:Female; D008099:Liver / Q000166:cytology / Q000378:metabolism; D009865:Oocytes / Q000378:metabolism; D029362:Organic Anion Transporters, Sodium-Independent / Q000378:metabolism*; D051381:Rats; D000074542:Solute Carrier Organic Anion Transporter Family Member 1B3; D013347:Subcellular Fractions / Q000378:metabolism; D013379:Substrate Specificity; D014018:Tissue Distribution; D014982:Xenopus laevis
D029362:Organic Anion Transporters, Sodium-Independent; C421102:Slco1a1 protein, rat; C421143:Slco1a5 protein, rat; C421207:Slco1b2 protein, rat; D000074542:Solute Carrier Organic Anion Transporter Family Member 1B3