title: The involvement of multidrug and toxin extrusion protein 1 in the distribution and excretion of berberine.
abstract: 1. Berberine (BBR), an isoquinoline alkaloid, has demonstrated multiple clinical pharmacological actions. As a substrate of multiple transporters in the liver, BBR is rarely excreted into the bile but can be found in the urine. The purpose of the present study was to investigate the role of multidrug and toxin extrusion protein 1 (MATE1) in the transport of BBR in the liver and kidney. 2. Using human MATE1 (hMATE1)-transfected HEK293 cells, BBR was shown to be a substrate of hMATE1 (Km= 4.28 ± 2.18 μM). In primary rat hepatocytes, pH-dependent uptake and efflux studies suggested that the transport of BBR was driven by the exchange of H+and involved Mate1. In rats, we found that pyrimethamine (PYR), an inhibitor of Mate1, increased hepatic and renal distribution of BBR and decreased systematic excretion of BBR. 3. These findings indicated that BBR is a substrate of MATE1 and that hepatic and renal Mate1 promote excretion of BBR into bile and urine, respectively. In conclusion, Mate1 plays a key role in the distribution and excretion of BBR, and we speculate that drug-drug interactions (DDIs) caused by MATE1 may occur between BBR and other co-administered drugs.
authors.affiliation: a Shanghai Institute of Materia Medica, Chinese Academy of Sciences , Shanghai , China and.|b University of Chinese Academy of Sciences , Beijing , China.
authors.forename: Ling
authors.initials: L
authors.lastname: Xiao
authors.affiliation: a Shanghai Institute of Materia Medica, Chinese Academy of Sciences , Shanghai , China and.|b University of Chinese Academy of Sciences , Beijing , China.
authors.forename: Yaru
authors.initials: Y
authors.lastname: Xue
authors.affiliation: a Shanghai Institute of Materia Medica, Chinese Academy of Sciences , Shanghai , China and.|b University of Chinese Academy of Sciences , Beijing , China.
authors.forename: Cuifeng
authors.initials: C
authors.lastname: Zhang
authors.affiliation: a Shanghai Institute of Materia Medica, Chinese Academy of Sciences , Shanghai , China and.|b University of Chinese Academy of Sciences , Beijing , China.
authors.forename: Le
authors.initials: L
authors.lastname: Wang
authors.affiliation: a Shanghai Institute of Materia Medica, Chinese Academy of Sciences , Shanghai , China and.|b University of Chinese Academy of Sciences , Beijing , China.
authors.forename: Yunfei
authors.initials: Y
authors.lastname: Lin
authors.affiliation: a Shanghai Institute of Materia Medica, Chinese Academy of Sciences , Shanghai , China and.|b University of Chinese Academy of Sciences , Beijing , China.
authors.forename: Guoyu
authors.initials: G
authors.lastname: Pan
mesh_terms: D000818:Animals; D001599:Berberine / Q000493:pharmacokinetics*; D002478:Cells, Cultured; D004347:Drug Interactions; D057809:HEK293 Cells; D022781:Hepatocytes / Q000187:drug effects / Q000378:metabolism; D006801:Humans; D006863:Hydrogen-Ion Concentration; D007668:Kidney / Q000187:drug effects / Q000378:metabolism; D008297:Male; D008687:Metformin / Q000493:pharmacokinetics; D027701:Organic Cation Transport Proteins / Q000378:metabolism*; D017207:Rats, Sprague-Dawley; D014018:Tissue Distribution
chemical_list: D027701:Organic Cation Transport Proteins; C521869:SLC47A1 protein, human; D001599:Berberine; D008687:Metformin
keywords: Berberine; DDIs; MATE1; excretion; hepatobiliary distribution