Vesicular neurotransmitter transporters as targets for endogenous and exogenous toxic substances

Exocytotic release of neurotransmitters requires their accumulation inside preformed secretory vesicles. Distinct vesicular transport activities translocate classical transmitters into synaptic vesicles energized by a H+ electrochemical gradient (Delta mu(H+)), with subtle but important differences in dependence on the electrical and chemical components. The vesicular transporters also interact with toxic compounds and drugs. They mediate neuroprotection by sequestering toxic compounds as well as neurotransmitters into vesicles, reducing their concentration in the cytosol where they may have detrimental effects. Both therapeutic agents and psychostimulants interfering with vesicular transport have yielded insight into the pathogenesis of psychiatric as well as neurodegenerative diseases. Thus, specific inhibitors have helped to characterize both the physiological role and mechanism of vesicular neurotransmitter transport.