The 2nd Croatian Symposium on Membrane Transporters (2. hrvatski simpozij o transporterima): Membrane Transporters in Toxicological and Pharmacological Research.

Numerous studies in the past 25 years have shown that most compounds, generated in metabolic processes (metabolic intermediates and products; endogenous compounds) or introduced orally or parenterally (nutritive compounds, medicaments, environmental toxins and other xenobiotics), do not enter or exit cells freely, by simple diffusion. Rather, their transmembrane movement is mediated by various membrane-bound proteins (transporters) localized in the cell membrane. Most membrane transporters belong to the SLC (SoLute Carriers) superfamily, which in humans encompass ~400 members grouped in 52 families (1). The functional properties and roles in cell physiology have been described for most of them, but about 40% of all SLCs are still orphans, without known substrates and biological characterization (1-5). The well-characterized members act as secondary-or tertiary-active exchangers, coupled transporters or electrochemically-driven facilitators in mediating the transport of amino acids, sugars, cholesterol, fatty acids, vitamins, inorganic ions, essential and some toxic metals, and various organic anions and cations, including drugs used in human and veterinary medicine. Depending on the electrochemical gradients of their substrates, these transporters can operate in influx or efflux mode, and are especially important in the intestine, liver and kidneys for handling the (re)absorptive and secretory processes. Due to their roles in the physiology of various organs, pathophysiology in various human diseases, and pharmacology (drug therapy, drug transport, drug-drug interactions, drug toxicity, drug development), the most characterized are the organic anion (OATs), cation (OCTs) and zwitterion transporters (family SLC22) (2-7), multidrug and toxins extruders (MATE/SLC47) (4, 8), and sodium-independent (GLUTs/SLC2) and sodium-dependent (SGLTs/SLC5) glucose transporters (9-11). Functional defects or malfunctions of the specific SLC transporters due to either inactive gene, diminished gene expression, or single nucleotide polymorphisms (SNPs)-dependent gene variants have been implicated in various human conditions and diseases, such as primary carnithine deficiency, rheumatoid arthritis, inflammatory bowel disease, cisplatin-induced toxicity, urolithiasis, mood-related disorders, diabetes, diminished renal secretion of organic anions and cations, variations in liver handling and renal secretion of organic cations, variations in drug pharmacokinetics and therapeutic efficiency, occurrence of drug-drug interactions and drug-induced organ toxicity, etc. (2, 4-6, 8). Another important superfamily of membrane transporters comprises several families of the primary-active ABC (ATP Binding Cassette) members that operate as the ATP-driven efflux pumps (12). Most renown of these transporters are multidrug resistance protein 1/P-glycoprotein (MDR1/P-gp/ABCB1), various MRPs (multidrug resistance associated proteins/ABCC family), and breast cancer