Transport systems are hydrophobic proteins localized in cell membranes where they mediate transmembrane
flow of nutrients, ions and any other compounds essential for cell metabolism. More than 400 transporters
of the SoLuteCarrier (SLC) group are present in human cells. Transporters take contacts also with xenobiotics,
thus mediating absorption and/or interaction with these exogenous compounds. Since drugs belong to xenobiotics,
transporters gained interest also in drug discovery. Transporters differentially expressed in pathological
conditions are exploited as drug targets. Among the methodologies for defining drug interactions, in silico ligand
screening and intact cell transport assay were the most diffused, so far. The first is a predictive methodology
based on docking chemicals to transporters. It presents limitations due to the small number of human transporter
3D structures that have to be constructed by homology modeling. Intact cells are used for testing effects of drugs
and for validating predictions. The challenges of handling this very complex experimental system, are the interferences
caused by other transporters and/or intracellular enzymes. Thus, methodologies with lower complexity
are welcome. One of the most updated is the proteoliposome nanotechnology consisting in a cell mimicking
phospholipid membrane in which a purified transporter is inserted. In this system, drug-transporter interaction can
be studied defining kinetics and mechanisms. Several data have been obtained by proteoliposome nanotechnology.
An overview of data obtained on the organic cation transporters OCTN1, OCTN2 and on the amino acid
transporters ASCT2 and B0AT1 will be presented. Standardized procedures, expected to be pointed out, will
enlarge the assay to High Throughput Screenings.
Keywords: Cell Membrane, liposome, drug, xenobiotics, SLC, amino acids, organic cations.
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