Abstract
Bile acids, the metabolites of cholesterol, are signaling molecules that play critical role in many physiological functions. They undergo enterohepatic circulation through various transporters expressed in intestine and liver. Human organic anion-transporting polypeptides (OATP) 1B1 and OATP1B3 contribute to hepatic uptake of bile acids such as taurocholic acid. However, the transport properties of individual bile acids are not well understood. Therefore, we selected HEK293 cells overexpressing OATP1B1 and OATP1B3 to evaluate the transport of five major human bile acids (cholic acid, chenodeoxycholic acid, deoxycholic acid, ursodeoxycholic acid, lithocholic acid) together withtheir glycine and taurine conjugates via OATP1B1 and OATP1B3. The bile acids were quantified by liquid chromatography-tandem mass spectrometry. The present study revealed that cholic acid, chenodeoxyxcholic acid, and deoxycholic acid were transported by OATP1B1 and OATP1B3, while ursodeoxycholic acid and lithocholic acid were not significantly transported by OATPs. However, all the conjugated bile acids were taken up rapidly by OATP1B1 and OATP1B3. Kinetic analyses revealed the involvement of saturable OATP1B1- and OATP1B3-mediated transport of bile acids. The apparent Km values for OATP1B1 and OATP1B3 of the conjugated bile acids were similar (0.74–14.7 μM for OATP1B1 and 0.47–15.3 μM for OATP1B3). They exhibited higher affinity than cholic acid (47.1 μM for OATP1B1 and 42.2 μM for OATP1B3). Our results suggest that conjugated bile acids (glycine and taurine) are preferred to unconjugated bile acids as substrates for OATP1B1 and OATP1B3.
Highlights
Bile acids are amphipathic steroidal molecules derived from cholesterol catabolism
We examined the uptake of Cholic acid (CA), chenodeoxycholic acid (CDCA), deoxycholic acid (DCA), ursodeoxycholic acid (UDCA), lithocholic acid (LCA), and their corresponding glycine and taurine conjugates by OATP1B1 and OATP1B3 in OATP1B1- and OATP1B3-overexpressing HEK293 cells, respectively
Acids are regarded as signaling molecules that play essential roles in many physiological effects. To execute their physiological effects, bile acids need to bind to their specific receptors such as farnesoid X receptor (FXR) and TGR5 that are expressed in liver and intestine and in tissues outside the enterohepatic circulation
Summary
Bile acids are amphipathic steroidal molecules derived from cholesterol catabolism. They are conjugated with amino acids, glycine and taurine, before being secreted into the bile. Cholic acid (CA) and chenodeoxycholic acid (CDCA) are the primary bile acids in humans. Deoxycholic acid (DCA) and lithocholic acid (LCA), are produced by gut microbiota from the primary bile acids. Bile acids play essential roles in many physiological functions such.
Sign-in/Register to view highlights & summary Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
