Interaction of porphyrins with human organic anion transporting polypeptide 1B1

摘要: Abstract The existence of a porphyrin uptake transporter in hepatocytes has been hypothesized recent years, but to date it not identified. While the linear tetrapyrrole bilirubin shown be substrate for organic anion transporting polypeptide 1B1 (OATP1B1), similar studies have conducted cyclic tetrapyrroles (porphyrins). aim this study was determine structural features and tetrapyroles necessary interaction with OATP1B1. quantified using HEK cells stably expressing OATP1B1 measuring inhibition OATP1B1-mediated estradiol 17β- d -glucuronide presence or absence various tetrapyrroles. Ditaurine-conjugated most potent inhibitor uptake, an IC50 5 nM, while substitution taurine side chains methyl ester eliminated uptake. Hematoporphyrin, carboxyalcohol at positions C-3 C-8 carboxyethyl 13 17 had 60 nM, porphyrins lacking charged such as etioporphyrin I phthalocyanine did inhibit Chlorin e6 hematoporphyrin were competitive inhibitors bromosulfophthalein Kis 5.8 ± 0.3 1.6 ± 0.3 μM, respectively. these do provide direct evidence, they support assumption that are transported by Additionally, findings offer possible explanation clinical observation patients suffering from certain porphyrietic diseases reduced ability excrete anions.