Ildikó Nagy, Beáta Tóth, Zsuzsanna Gáborik, Franciska Erdo and Péter Krajcsi Pages 5347 - 5372 ( 26 )
Membrane transporters expressed in barrier forming cell types provide a dual filtration system as unwanted xenobiotics are effluxed by ABC transporters, and compounds essential for the organism, such as nutrients or physiological substrates, are taken up by influx transporters. The majority of efflux transporters apically-localized in barrier forming cell types are ABC transporters that may limit absorption or distribution, and promote excretion. Pharmaceutical scientists are increasingly aware of the limitations these efflux transporters represent. Influx transporters are also critically important, as apically-located influx transporters may counteract the effect of co-localized efflux transporters, promoting absorption or reabsorption, as well as facilitating distribution of low passive permeability substrates into tissues that are otherwise heavily guarded by efflux transporters. In excretory organs, basolaterally-localized influx transporters cooperate with apically-localized efflux trransporters to efficiently drive transcellular movement of xenobiotics and their metabolites. Pharmacological inhibition of absorption or reabsorption of unwanted nutrients and endobiotics has become a great opportunity for pharmaceutical development. For drug developers, these transporters also offer the opportunity to target specific organs and cell types. Targeting drugs to cells and tissues harboring the pharmacological target not only makes drugs more efficient, but can also make them less toxic, as it allows for administration of lower doses and less distribution of drugs into non-target organs.
ABC transporters, drug development, SLC transporters, tissue barriers, intestine, liver, kidney, brain.
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