The neurochemical bases of the pharmacological activity of ligands of monoamine-transport systems

In Vitro Assays for the Functional Characterization of the Dopamine Transporter (DAT)

“…The substrate binding site is located between TM1 and 6. Intra-(IL) and extracellular (EL) loops are numbered from 1 to 6. synaptic cleft into the pre-synaptic neuronal terminals (Kristensen et al, 2011), where the transmitters are either sequestered into synaptic vesicles through vesicular monoamine transporters (Golovko, Bonitenko, Ivanov, Barinov, & Zatsepin, 2016) for recycling or are degraded by monoamine oxidase. Along with the transport of one molecule of monoamine neurotransmitter, MATs also co-transport two Na + ions and one or more Clions into the intracellular space.…”

“…In addition to the substrate binding site, these studies have revealed the presence of additional ligand attachment sites within MATs of which the location and functional relevance remain unknown (Coleman, Green, & Gouaux, , Koldso et al., , Mortensen & Kortagere, , Rothman et al., ). The MATs mediate a rapid uptake of neurotransmitters (turnover rate ∼1 molecule/sec) from the synaptic cleft into the pre‐synaptic neuronal terminals (Kristensen et al., ), where the transmitters are either sequestered into synaptic vesicles through vesicular monoamine transporters (Golovko, Bonitenko, Ivanov, Barinov, & Zatsepin, ) for recycling or are degraded by monoamine oxidase. Along with the transport of one molecule of monoamine neurotransmitter, MATs also co‐transport two Na + ions and one or more Cl – ions into the intracellular space.…”