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.
Chaudhry
Farrukh A
FA
Centre for Molecular Biology and Neuroscience, The Biotechnology Centre of Oslo, University of Oslo, Oslo, Norway. f.a.chaudhry@biotek.uio.no
Edwards
Robert H
RH
Fonnum
Frode
F
D000818:Animals; D001692:Biological Transport / Q000187:drug effects / Q000502:physiology; D006801:Humans; D001523:Mental Disorders / Q000503:physiopathology; D019636:Neurodegenerative Diseases / Q000503:physiopathology; D018377:Neurotransmitter Agents / Q000378:metabolism*; D009435:Synaptic Transmission / Q000187:drug effects / Q000502:physiology; D013572:Synaptic Vesicles / Q000187:drug effects / Q000378:metabolism*; D050481:Vesicular Neurotransmitter Transport Proteins / Q000378:metabolism*
D018377:Neurotransmitter Agents; D050481:Vesicular Neurotransmitter Transport Proteins