Electrogenic voltage-dependent transporter that mediates the transport of a variety of endogenous bioactive amines, cationic xenobiotics and drugs (    ). Utilizes the physiologic inside-negative membrane potential as a driving force to facilitate cellular uptake of organic cations ( ). Functions as a Na(+)- and Cl(-)-independent bidirectional transporter ( , ). Substrate transport is pH-dependent and enhanced under acidic condition, which is most likely the result of allosteric changes in the transporter structure (  ). Implicated in monoamine neurotransmitters uptake such as serotonin, dopamine, adrenaline/epinephrine, noradrenaline/norepinephrine, histamine and tyramine, thereby supporting a role in homeostatic regulation of aminergic neurotransmission in the central nervous system (  , ). Also responsible for the uptake of bioactive amines and drugs through the blood-cerebrospinal fluid (CSF) barrier, from the CSF into choroid plexus epithelial cells, thereby playing a significant role in the clearance of cationic neurotoxins, xenobiotics and metabolic waste in the brain (By similarity). Involved in bidirectional transport of the purine nucleoside adenosine and plays a role in the regulation of extracellular adenosine concentrations in cardiac tissues, in particular during ischemia ( ). May be involved in organic cation uptake from the tubular lumen into renal tubular cells, thereby contributing to organic cation reabsorption in the kidney . Also transports guanidine .
Subcellular locations: Cell membrane, Apical cell membrane
Located to the plasma membranes of ventricular myocytes and vascular endothelial cells . Targeted to the apical membranes of differentiated kidney epithelial cells . Localized to the apical blood-cerebrospinal fluid (CSF)-facing membrane of the choroid plexus epithelium .
Mainly expressed in brain and skeletal muscle ( , ). In brain, expressed in cerebellum, cerebral cortex, medulla oblongata, occipital pole, frontal and temporal lobes putamen, spinal cord, substancia nigra, hippocampus, caudate nucleus, nucleus accumbens, pons and choroid plexus ( , ). Expressed in heart, in both cardiomyocytes and vascular endothelial cells ( ). Also expressed in adrenal gland, small intestine, pancreas, kidney, liver, bone marrow, lymph node ( , ). Located in endometrial stroma, where the expression is high in the proliferative phase, decreases during the secretory phase, and is no longer detectable in the menstrual phase .