Assessing Vesicular Monoamine Transport and Toxicity Using Fluorescent False Neurotransmitters.
Journal
Chemical research in toxicology
ISSN: 1520-5010
Titre abrégé: Chem Res Toxicol
Pays: United States
ID NLM: 8807448
Informations de publication
Date de publication:
17 05 2021
17 05 2021
Historique:
pubmed:
31
12
2020
medline:
16
11
2021
entrez:
30
12
2020
Statut:
ppublish
Résumé
Impairments in the vesicular packaging of dopamine result in an accumulation of dopamine in the cytosol. Cytosolic dopamine is vulnerable to two metabolic processes-enzymatic catabolism and enzymatic- or auto-oxidation-that form toxic metabolites and generate reactive oxygen species. Alterations in the expression or activity of the vesicular monoamine transporter 2 (VMAT2), which transports monoamines such as dopamine from the cytosol into the synaptic vesicle, result in dysregulated dopamine packaging. Here, we developed a series of assays using the fluorescent false neurotransmitter 206 (FFN206) to visualize VMAT2-mediated vesicular packaging at baseline and following pharmacological and toxicological manipulations. As a proof of principle, we observed a significant reduction in vesicular FFN206 packaging after treatment with the VMAT2 inhibitors reserpine (IC
Identifiants
pubmed: 33378168
doi: 10.1021/acs.chemrestox.0c00380
pmc: PMC8131219
mid: NIHMS1677545
doi:
Substances chimiques
Neurotransmitter Agents
0
SLC18A2 protein, human
0
Vesicular Monoamine Transport Proteins
0
Types de publication
Journal Article
Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
1256-1264Subventions
Organisme : NIEHS NIH HHS
ID : T32 ES012870
Pays : United States
Organisme : NIEHS NIH HHS
ID : T32 ES007322
Pays : United States
Organisme : NIEHS NIH HHS
ID : R01 ES023839
Pays : United States
Organisme : NIEHS NIH HHS
ID : P30 ES019776
Pays : United States
Organisme : NIDA NIH HHS
ID : U18 DA052498
Pays : United States
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