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.
Keywords: ABC transporters, drug development, SLC transporters, tissue barriers, intestine, liver, kidney, brain.
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