Annu Rev Pharmacol Toxicol. 2008;48:277-301.
Vesicular neurotransmitter transporters as targets for endogenous and exogenous toxic substances.

Chaudhry FA, Edwards RH, Fonnum F.
Centre for Molecular Biology and Neuroscience, The Biotechnology Centre of Oslo, University of Oslo, Oslo, Norway. f.a.chaudhry@biotek.uio.no

Abstract
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.

PMID: 17883368 [PubMed - indexed for MEDLINE]

http://www.ncbi.nlm.nih.gov/pubmed/17883368



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vesicular transporters


helpful background:

A biological membrane or biomembrane is an enclosing or separating membrane that acts as a selective barrier, within or around a cell. It consist of a lipid bilayer with embedded proteins that may constitute close to 50% of membrane content.[1]. The cellular membranes should not be confused with isolating tissues formed by layers of cells, such as mucous and basement membranes.


Biological membranes consist of a phospholipidbilayer and a variety of proteins that accomplish vital biological functions.

http://en.wikipedia.org/wiki/Membrane_protein#Function

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looks like excitatory transmitters can be toxic as well as dopamine wiithout it protective mechanism. much more coming here but i wondered if gaba could be toxic...our brake system that surely many of us are lacking.

GABA is toxic for mouse striatal neurones through a transporter-mediated process.
Maus M, Glowinski J, Premont J.
INSERM U114, College de France, Paris, France.
Abstract

In the present study, GABA was shown to induce a necrotic neuronal death in cultured striatal neurones from mouse embryos. This effect did not depend on the activation of GABA(A), GABA(B) or GABA(C) receptors as it was neither antagonized by bicuculline, saclofen or picrotoxin, respectively, nor reproduced by the GABA receptor agonists, muscimol and baclofen. Excluding the participation of glutamate, GABA neurotoxicity persisted in the presence of either the antagonists of ionotropic and metabotropic glutamate receptors or glutamate pyruvate transaminase, which induces an immediate catabolism of glutamate. A GABA transport-associated process is involved in GABA neurotoxicity as nipecotic acid and NO 711, two inhibitors of the high-affinity neuronal GABA transporters (GAT-1, in particular), completely prevented the neurotoxic effect of GABA. The activation of a subset of G proteins is also implicated in the GABA transport-mediated neuronal death as GABA neurotoxicity was completely suppressed when striatal neurones were pre-treated with pertussis toxin. Further demonstrating the specificity of this neurotoxic process, GABA-induced neurotoxicity was not observed in cortical neurones which, in contrast to striatal neurones, are largely represented by glutamatergic neurones. In conclusion, our study suggests that glutamate is not the sole neurotransmitter that can be responsible for brain damage and that GABA neurotoxicity involves both GABA transport and G protein transduction pathways.

PMID: 12358781 [PubMed - indexed for MEDLINE]

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more to come. Imad has been studying l dopa and it occurred to me that transmitters [at least excitatory ones] are all toxic. feel free to add i'm just getting started. trying to learn the background first. researchers, explain and expand and correct me on mistakes. i think we can be at the table if we learn this stuff and stay current.