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Xenopus oocyte and Chinese hamster ovary (CHO) cell heterologous expression systems were employed in the investigation of the subjects specificity of the sodium ion-taurocholate cotransporting polypeptide (Ntcp). Results show that other bile salts inhibited the transport of taurocholate in CHO cell line expressing Ntcp and Xenopus oocytes expressing Ntcp are able to transport other bile salts and sterones. These results indicate that Ntcp is a multispecific cotransporter.

A study was conducted on the mechanisms associated with the short-term stimulation of Na+-taurocholate cotransport induced by adenosine 3',5'-cyclic monophosphate (cAMP). Plasma membrane vesicle investigations reveal that the protein kinase catalytic subunit does not stimulate taurocholate uptake. Results also suggest that Na+-taurocholate cotransport transport maximum is enhanced in part through transporter translocation to plasma membranes.

The rat organic anion transport protein (oatp) is present mainly in the apical membrane of the proximal tubule of the renal outer medulla and in the basolateral plasma membrane in the liver. The differential basolateral and apical subcellular distribution of oatp is due to differential biosynthetic processing and transport. Reduction of the protein in the kidney produces a 33 and a 37 kDa peptide, but has no effect on the protein in the liver. The liver protein is abundant in Na2CO3-extracted membranes and sinusoidal plasma membrane preparations.

A functional-expression cloning technique facilitated the identification and characterization of a cDNA encoding a rat liver basolateral Na+-independent organic anion transporting polypeptide (Oatp), which mediates Na+-independent utilization of sulfobromophthalein. The cDNA encoding Oatp comprised an open reading frame of 2010 nucleotides which featured coding sequences for a protein containing 670 amino acids. Translation experiments confirmed previously predicted glycosylation sites of the protein, and indicated the glycosylated state of the transporter.

Abstract Background Raloxifene, a selective estrogen receptor modulator, exhibits quite large and unexplained interindividual variability in pharmacokinetics and pharmacodynamics. The aim of this study was to determine the role of organic-anion transporting polypeptides OATP1B1 and OATP1B3 and their genetic variants in the pharmacokinetics and pharmacodynamics of raloxifene. Methods To test the role of OATP1B1 and OATP1B3 transporters on hepatic uptake of raloxifene and its metabolites an in vitro model of Chinese Hamster Ovary cells expressing OATP1B1 or OATP1B3 was employed. The influence of OATP1B1 and OATP1B3 genetic variants on in vivo pharmacokinetics and pharmacodynamics was evaluated in 53 osteoporotic postmenopausal women treated with raloxifene. Results Our in vitro results showed that raloxifene and two of the three metabolites, raloxifene-4'-β-glucuronide (M2) and raloxifene-6,4'-diglucuronide (M3), interact with OATP1B1 and OATP1B3. Higher M3 and total raloxifene serum concentrations in patients correlated with lower serum levels of bone resorption marker, serum C-terminal telopeptide fragments of type I collagen, indicating a higher antiresorptive effect of raloxifene. Higher concentrations of M2 correlated with higher increase of lumbar spine bone mineral density supporting the raloxifene vertebral fracture specific protection effect. Finally, raloxifene, M3 and total raloxifene serum concentrations were significantly higher in patients with SLCO1B1 c.388A > G polymorphism and *1b haplotype implicating a considerable genetic effect on pharmacokinetics and pharmacodynamics of raloxifene. Conclusions These findings indicate that SLCO1B1 c.388A > G polymorphism could play an important role in pharmacokinetics and pharmacodynamics of raloxifene.