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The inhibitory effects of five alkaloids on the substrate transport mediated through human organic anion and cation transporters.
- Source :
- Xenobiotica; Feb2018, Vol. 48 Issue 2, p197-205, 9p
- Publication Year :
- 2018
-
Abstract
- 1. Human solute carrier transporters (SLCs) are important membrane proteins mediate the cellular transport of many endogenous and exogenous substances. Organic anion/cation transporters (OATs/OCTs) and organic anion transporting polypeptides (OATPs) are essential SLCs involved in drug influx. Drug–drug/herb interactions through competing for specific SLCs often lead to unsatisfied therapeutic outcomes and/or unwanted side effects. In this study, we comprehensively investigated the inhibitory effects of five clinically relevant alkaloids (dendrobine, matrine, oxymatrine, tryptanthrin and chelerythrine) on the substrate transport through several OATs/OCTs and OATPs. 2. We performed transport functional assay and kinetic analysis on the HEK-293 cells over-expressing each SLC gene. 3. Our data showed tryptanthrin significantly inhibited the transport activity of OAT3 (IC50 = 0.93 ± 0.22 μM, Ki = 0.43 μM); chelerythrine acted as a potent inhibitor to the substrate transport mediated through OATP1A2 (IC50 = 0.63 ± 0.43 μM, Ki = 0.60 μM), OCT1 (IC50 = 13.60 ± 2.81 μM) and OCT2 (IC50 =10.80 ± 1.16 μM). 4. Our study suggested tryptanthrin and chelerythrine could potently impact on the drug transportviaspecific OATs/OCTs. Therefore, the co-administration of these alkaloids with drugs could have clinical consequences due to drug–drug/herb interactions. Precautions should be warranted in the multi-drug therapies involving these alkaloids. [ABSTRACT FROM PUBLISHER]
Details
- Language :
- English
- ISSN :
- 00498254
- Volume :
- 48
- Issue :
- 2
- Database :
- Complementary Index
- Journal :
- Xenobiotica
- Publication Type :
- Academic Journal
- Accession number :
- 126917396
- Full Text :
- https://doi.org/10.1080/00498254.2017.1282647