Involvement of organic anion-transporting polypeptides and organic cation transporter in the hepatic uptake of jatrorrhizine

Xenobiotica; the Fate of Foreign Compounds in Biological Systems
Rui-Feng LiangGeng-Sheng Li

Abstract

Jatrorrhizine possesses a wide spectrum of pharmacological activities. However, the mechanism underlying hepatic uptake of jatrorrhizine remains unclear. Rat liver slices, isolated rat hepatocytes and human embryonic kidney 293 (HEK293) cells stably expressing human organic anion-transporting polypeptide (OATP) and organic cation transporter (OCT) were used to evaluate the hepatic uptake of jatrorrhizine in this study. Uptake of jatrorrhizine in rat liver slices and isolated rat hepatocytes was significantly inhibited by glycyrrhizic acid (Oatp1b2 inhibitor) and prazosin (Oct1 inhibitor), but not by ibuprofen (Oatp1a1 inhibitor) or digoxin (Oatp1a4 inhibitor). Uptake of jatrorrhizine in OATP1B3 and OCT1-HEK293 cells indicated a saturable process with the Km of 8.20 ± 1.28 and 4.94 ± 0.55 μM, respectively. However, the transcellular transport of jatrorrhizine in OATP1B1-HEK293 cells was not observed. Rifampicin (OATP inhibitor) for OATP1B3-HEK293 cells and prazosin for OCT1-HEK293 cells could inhibit the uptake of jatrorrhizine with the IC50 of 5.49 ± 1.05 and 2.77 ± 0.72 μM, respectively. The above data indicate that hepatic uptake of jatrorrhizine is involved in both OATP and OCT, which may have important roles in jatrorrhizin...Continue Reading

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Citations

Mar 9, 2021·Frontiers in Pharmacology·Shiwei ZhouYan Shu
May 7, 2021·Xenobiotica; the Fate of Foreign Compounds in Biological Systems·Xian-Mei SongRui-Feng Liang

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