Disease relevance of Slco1b2

• The expression of rlst-1 may be under feedback regulation of cholestasis by biliary obstruction and/or sepsis [1].

High impact information on Slco1b2

• The Km value in rat hepatocytes is consistent with Oatp4-mediated transport [2].
• In both the bile duct ligation model and the cecum ligation and puncture model, mRNA expression levels of rlst-1 were down-regulated [1].
• Accordingly, Oatp4 protein was significantly down-regulated in CA-fed animals together with Oatp1 and Ntcp [3].
• Oatp4 messenger RNA (mRNA) levels did not differ significantly between bile salt-fed groups, suggesting a posttranscriptional effect of CA on Oatp4 expression [3].
• Cofeeding of CA plus UDCA prevented the impairment of (14)C-CA and (14)C-TCA secretion and the down-regulation of Oatp4 [3].

Chemical compound and disease context of Slco1b2

• In conclusion, we show that CA feeding may cause cholestasis associated with a posttranscriptional down-regulation of Oatp4 [3].

Biological context of Slco1b2

• The rlst-1 gene is composed of 15 exons and 14 introns [4].
• 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 [5].
• The tissue distribution of Oatp4 was almost exclusively expressed in liver in contrast to Oatp1, 2, 3, and 5 [6].
• The preference of Oatp4 for endogenous compounds coupled with its refractory response to known drug-metabolizing enzyme inducers suggests that Oatp4 may be largely responsible for the homeostasis of endogenous rather than exogenous chemicals, including pharmaceuticals [6].

Anatomical context of Slco1b2

• When expressed in Xenopus laevis oocytes, Oatp4 (Slc21a10) mediated polyspecific uptake of a variety of organic anions including taurocholate (K(m) approximately 27 microM), bromosulfophthalein (K(m) approximately 1.1 microM) and steroid conjugates [7].
• 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 [5].
• The abundance of their mRNA in rat trophoblast was Oatp1/1a1 >> Oatp4/1b2 > Oatp2/1a4 [8].

Associations of Slco1b2 with chemical compounds

• Similar to Oatp1 and Oatp2, Oatp4 is a multispecific transporter with high affinities for bromosulfophthalein, dehydroepiandrosterone sulfate, leukotriene C4, and anionic peptides [5].

Analytical, diagnostic and therapeutic context of Slco1b2

• Northern blot analyses were performed using the isolated cDNA (termed rlst-1) [1].

References