High impact information on Slco1a1

• RT-PCR analysis revealed that oatp3 mRNA is expressed in brain capillary-rich fraction, conditionally immortalized brain capillary endothelial cells, choroid plexus, brain and lung, but not in liver or kidney, where oatp1, 2 and 5 mRNAs were detected [1].
• The bile salt uptake system Na(+)-taurocholate co-transporting polypeptide (Ntcp) and organic anion transporting polypeptide-1 (Oatp1) were down-regulated by taurocholate and not affected by cholestyramine feeding [2].
• When expressed in Xenopus laevis oocytes, the mouse Oatp exhibited the same substrate specificity as the rat Oatp1 [3].
• Using fluorescence in situ hybridization, the murine Oatp1 gene was mapped to chromosome XA3-A5 [3].
• Taken together, the amino acid identity, the functional characteristics and the tissue distribution suggest that we have isolated the murine orthologue of the rat Oatp1, and consequently the identified protein will be called Oatp1 [3].

Biological context of Slco1a1

• In the present study we describe the strict androgen-dependent expression of mouse Oatp1 mRNA in kidney and obtained further information about its substrate specificity using Xenopus oocytes [4].
• The cloned cDNA insert of 2783 bp with an open reading frame of 2011 bp codes for a 12-transmembrane 670-amino-acid protein with highest amino acid identity with the rat Oatp1 [3].
• Hepatic Oatp uptake of some chemicals must occur prior to biotransformation; thus, we hypothesize that expression of Oatps and biotransformation enzymes is coordinately regulated in liver [5].

Anatomical context of Slco1a1

• A weak cytostatic effect of BANB-1, BANB-2 and BANB-3 was detected even in CHO cells stably transfected with rat bile acid transporters (Ntcp and Oatp1/1a1) [6].
• P-glycoprotein (P-gp) and organic anion transporting polypeptides (Oatp) are expressed at the blood-brain barrier (BBB) [7].
• An inhibitor of OATP, rifampicin, partly protected hepatocytes from this damage [8].
• The lack of sensitivity of the trout cell lines coincided with an absence of detectable mRNA levels of organic anion transporter polypeptide (OATP), which is implicated in the uptake of microcystin-LR [8].
• In FXR-null mice, the mRNA levels of oatp1, oatp2, oatp3, and octn1 were lower than those of wild-type mice in kidney and testis, while there was no difference in liver or small intestine [9].

Associations of Slco1a1 with chemical compounds

• Bile acid treatment increased the in vivo expression of Bsep but not Mrp or Oatp [10].
• In addition to the previously reported estrone-3-sulfate, we demonstrate that mouse Oatp1 mediates sodium-independent uptake of the anionic steroid conjugates dehydroepiandrosterone sulfate (K(m) approximately 8 microM) and estradiol-17-glucuronide (K(m) approximately 5 microM) and also of the prostaglandin PGE(2) [4].
• Besides the common Oatp substrates bromosulphophthalein, taurocholate, oestrone 3-sulphate and ouabain, the new mouse Oatp also mediates transport of the Oatp1-specific magnetic-resonance-imaging agent gadoxetate [3].
• These results confirm P-gp-mediated efflux of DPDPE, and suggest functional uptake transport of DPDPE by Oatp, at the murine BBB [7].
• Cholic acid feeding led to significantly decreased levels of expression of oatp1 and oct1 and an increased level of expression of oatp2 in wild-type mouse liver [9].

Physical interactions of Slco1a1

• Functional analysis and androgen-regulated expression of mouse organic anion transporting polypeptide 1 (Oatp1) in the kidney [4].

Other interactions of Slco1a1

• However, the mechanisms by which the Oatp and Mrp genes are down-regulated are largely unknown [10].
• Cyp7A(-/-) mice did not show altered Ntcp or Oatp1 expression [2].
• These data indicate that disruption of HNF1alpha causes a marked attenuation of several Oat and Oatp uptake transporters in liver and kidney, and increased expression of efflux transporters such as Mdrs and Mrps, thus suggesting that HNF1alpha is a central mediator in regulating hepatic, renal, and intestinal transporters [11].

Analytical, diagnostic and therapeutic context of Slco1a1

• RT-PCR analysis revealed the expression of mRNA of numerous transporters including MRP, OATP, MCT and OCTN family members in hairless mouse skin, human skin and HEK001 cells [12].
• Northern blot analysis detected expression of several mouse Oatp-transcripts predominantly in liver and kidney [4].
• Molecular cloning and functional characterization of the mouse organic-anion-transporting polypeptide 1 (Oatp1) and mapping of the gene to chromosome X [3].

References