We did cell uptake inhibitors experiments (both FACS and confocol for Mn(II) complex), 4oC low temperature could deducted ~ 25% uptake. It was quit odd that several inhibitors we've tried including NH4Cl, Choroquine, colchicine and 2-deoxy-Dglucose/oligomycin significantly enhanced the cell uptake(from 20% to 70%), any good explanation?
Hey Joe, did you tox test your endocytosis inhibitors to make sure you were using them at viable concentrations?
Hi Xiaohe, some of these compounds (e.g. NH4Cl, Choroquine) do not inhibit endocytosis. They inhibit lysosome activity. Inhibit lysosomes and the compounds just accumulate in the cells.
If the metallic compound in question is a substrate of a multidrug efflux transporter such as P-gp or MRP, then adding another compound that is also a substrate (colchicine and chloroquine), or that acts as an inhibitor, will enhance the uptake of the metallic compound by reducing the effectiveness of the transporter. Additionally, since these transporters are energy-dependent, any treatment that de-energizes the cell (deoxyglucose/oligomycin) will also enhance uptake of the compound.
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