Localization of organic anion transporting polypeptide 4 (Oatp4) in rat liver and comparison of its substrate specificity with Oatp1, Oatp2 and Oatp3

Abstract

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.

Localization of organic anion transporting polypeptide 3 (oatp3) in mouse brain parenchymal and capillary endothelial cells

“…On the other hand, the expression of oatp3 at the BBB can explain an important BBB function which is not mediated by oatp2 or 14, i.e. PGE 2 is a substrate of oatp3, whereas oatp2 and 14 do not transport it (Cattori et al 2001;Sugiyama et al 2003). PGE 2 functions as a signal to the brain of peripheral inflammation (Engblom et al 2002).…”

“…We have reported that oatp3 is localized at the rat choroid plexus (Ohtsuki et al 2003) and this finding raises the issue of whether oatp3 is expressed at the brain capillaries. Oatp3 accepts prostaglandin E 2 (PGE 2 ) as a substrate, whereas oatp2 and oatp14 do not (Cattori et al 2001;Sugiyama et al 2003). PGE 2 functions as a mediator of peripheral inflammation to the brain across the BBB (Engblom et al 2002).…”

Molecular and ionic mimicry and the transport of toxic metals

“…Several transport proteins that may be involved in this transport include the organic anion transporting polypeptides, OATP1, OATP2, and OATP4 (Cattori et al, 2001;Jacquemin et al, 1994;Kullak-Ublick et al, 1994), the organic cation transporter, OCT1 (Grundemann et al, 1994), the metal transport protein, MTP1 (Abboud and Haile, 2000) and amino acid or peptide transporters that are localized in the sinusoidal plasma membrane. Although these carriers have not been implicated in the transport of metals out of hepatocytes, most of them are multispecific transporters and may be able to carry metal ions or conjugated forms of metals.…”

Gd-BOPTA Transport Into Rat Hepatocytes: Pharmacokinetic Analysis of Dynamic Magnetic Resonance Images Using a Hollow-Fiber Bioreactor

“…Rabbit polyclonal antibodies against rat Oatp1 (Slc21a1), 16,17 rat Oatp2 (Slc21a5), 18 rat Oatp4 (Slc21a10), 19 and rat Mrp2 (Abcc2) 20 were used. Sodium dodecyl sulfate …”