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closeCationic amphipaths strike again
Posted by eperlste on 08 Aug 2012 at 04:11 GMT
Interesting article! As stated in the introduction of the paper, quinacrine has been shown to have numerous effects on cellular physiology, thus meeting the textbook definition of polypharmcology.
My question pertains to the membrane accumulation of quinacrine. During the tissue homogenization step, it doesn't appear that detergent was present. Is that correct? I'm wondering if membrane-associated quinacrine is registered in the final concentration measurements. The acetonitrile extraction would solubilize all quinacrine present in the samples, but it's not clear to me from the Methods section what comprises the "homogenate."
My lab published a PLOS ONE paper back in April describing the membrane accumulation of radiolabeled sertraline (Zoloft) in yeast cells: http://www.plosone.org/ar.... We interpreted experiments using energy poisons to mean that efflux pumps constitutively regurgitate sertraline, presumably as an ionized species. Similar to this study, we found a ~10-fold increase in sertraline uptake when efflux was inhibited.
So I would agree that any therapeutic strategy involving cationic amphipaths hitting a primary set of targets would be enhanced by general efflux inhibitors.