Comparative Study
doi: 10.1016/j.ejphar.2008.06.079. Epub 2008 Jun 27.Interaction of plant cannabinoids with the multidrug transporter ABCC1 (MRP1)
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- PMID:18619955
- DOI: 10.1016/j.ejphar.2008.06.079
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Comparative Study
Interaction of plant cannabinoids with the multidrug transporter ABCC1 (MRP1)
Michelle L Holland et al. Eur J Pharmacol..
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Abstract
The ATP-binding cassette (ABC) transporter ABCC1, or multidrug resistance-related protein 1 (MRP1) is implicated in Phase II metabolism and multidrug resistance as it effluxes substrate anticancer drugs. As cannabinoids inhibit two related ABC transporters, P-glycoprotein and ABCG2, here we examined whether they also inhibit ABCC1. Indeed, the cannabinoids enhanced the intracellular accumulation of two ABCC1 substrates, Fluo3 and vincristine, in ovarian carcinoma cells over-expressing ABCC1 (2008/MRP1) with a rank order of potency: cannabidiol>cannabinol>Delta(9)-tetrahydrocannabinol. Cannabinoid inhibition of ABCC1 was confirmed using insect cell membrane MRP1 ATPase assays. These results demonstrate that cannabinoids inhibit ABCC1.
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