An in vitro study on interaction of anisodine and monocrotaline with organic cation transporters of the SLC22 and SLC47 families  

作　　者：CHEN Jia-Yin Jürgen Brockmoller Mladen V.Tzvetkov WANG Li-Jun CHEN Xi-Jing 

机构地区：[1]Department of Pharmacy, Peking University Shenzhen Hospital, Shenzhen 518036, China [2]Institute for Clinical Pharmacology, University Medical Center Gottingen, Georg-August University, Gottingen 37075, Germany [3]Clinical Pharmacokinetics Lab, China Pharmaceutical University, Nanjing 211198, China

出　　处：《Chinese Journal of Natural Medicines》2019年第7期490-497,共8页中国天然药物（英文版）

基　　金：supported by the Natural Science Foundation of Guangdong Province(No.2018A0303100026);German Research Foundation(DFG) Grant Clinical Research Group “Genotype-phenotype relationships and neurobiology of the longitudinal course of psychosis” in work package 3(No. BR2471/1-1) and DFG Grant(No. TZ74/1-1)

摘　　要：Current study systematically investigated the interaction of two alkaloids, anisodine and monocrotaline, with organic cation transporter OCT1, 2, 3, MATE1 and MATE2-K by using in vitro stably transfected HEK293 cells. Both anisodine and monocrotaline inhibited the OCTs and MATE transporters. The lowest IC50 was 12.9 μmol·L-1 of anisodine on OCT1 and the highest was 1.8 mmol·L-1 of monocrotaline on OCT2. Anisodine was a substrate of OCT2(Km = 13.3 ± 2.6 μmol·L-1 and Vmax = 286.8 ± 53.6 pmol/mg protein/min). Monocrotaline was determined to be a substrate of both OCT1(Km = 109.1 ± 17.8 μmol·L^-1, Vmax = 576.5 ± 87.5 pmol/mg protein/min) and OCT2(Km = 64.7 ± 14.8 μmol·L^-1, Vmax = 180.7 ± 22.0 pmol/mg protein/min), other than OCT3 and MATE transporters. The results indicated that OCT2 may be important for renal elimination of anisodine and OCT1 was responsible for monocrotaline uptake into liver. However neither MATE1 nor MATE2-K could facilitate transcellular transport of anisodine and monocrotaline. Accumulation of these drugs in the organs with high OCT1 expression(liver) and OCT2 expression(kidney) may be expected.Current study systematically investigated the interaction of two alkaloids, anisodine and monocrotaline, with organic cation transporter OCT1, 2, 3, MATE1 and MATE2-K by using in vitro stably transfected HEK293 cells. Both anisodine and monocrotaline inhibited the OCTs and MATE transporters. The lowest IC50 was 12.9 μmol·L-1 of anisodine on OCT1 and the highest was 1.8 mmol·L-1 of monocrotaline on OCT2. Anisodine was a substrate of OCT2(Km = 13.3 ± 2.6 μmol·L-1 and Vmax = 286.8 ± 53.6 pmol/mg protein/min). Monocrotaline was determined to be a substrate of both OCT1(Km = 109.1 ± 17.8 μmol·L-1, Vmax = 576.5 ± 87.5 pmol/mg protein/min) and OCT2(Km = 64.7 ± 14.8 μmol·L-1, Vmax = 180.7 ± 22.0 pmol/mg protein/min), other than OCT3 and MATE transporters. The results indicated that OCT2 may be important for renal elimination of anisodine and OCT1 was responsible for monocrotaline uptake into liver. However neither MATE1 nor MATE2-K could facilitate transcellular transport of anisodine and monocrotaline. Accumulation of these drugs in the organs with high OCT1 expression（liver） and OCT2 expression（kidney） may be expected.

关 键 词：ANISODINE MONOCROTALINE Organic CATION TRANSPORTER OCT MATE 

分 类 号：R965[医药卫生—药理学]