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@article{1473627,
author = {Henke, Adam and Kovalyova, Yekaterina and Dunn, Matthew and Dreier, Dominik and Gubernator, Niko G. and Dincheva, Iva and Hwu, Christopher and Šebej, Peter and Ansorge, Mark S. and Sulzer, David and Sameš, Dalibor},
article_location = {WASHINGTON},
article_number = {5},
doi = {http://dx.doi.org/10.1021/acschemneuro.7b00320},
keywords = {FFN246; fluorescent false neurotransmitters; serotonin; 5-HT; monoaminergic neurons; imaging probe},
language = {eng},
issn = {1948-7193},
journal = {ACS CHEMICAL NEUROSCIENCE},
note = {Žádný z autorů nemá afiliaci k MU, nelze tedy výsledek přenášet do RIV.},
title = {Toward Serotonin Fluorescent False Neurotransmitters: Development of Fluorescent Dual Serotonin and Vesicular Monoamine Transporter Substrates for Visualizing Serotonin Neurons},
url = {https://pubs.acs.org/doi/abs/10.1021/acschemneuro.7b00320},
volume = {9},
year = {2018}
}
TY - JOUR
ID - 1473627
AU - Henke, Adam - Kovalyova, Yekaterina - Dunn, Matthew - Dreier, Dominik - Gubernator, Niko G. - Dincheva, Iva - Hwu, Christopher - Šebej, Peter - Ansorge, Mark S. - Sulzer, David - Sameš, Dalibor
PY - 2018
TI - Toward Serotonin Fluorescent False Neurotransmitters: Development of Fluorescent Dual Serotonin and Vesicular Monoamine Transporter Substrates for Visualizing Serotonin Neurons
JF - ACS CHEMICAL NEUROSCIENCE
VL - 9
IS - 5
SP - 925-934
EP - 925-934
PB - AMER CHEMICAL SOC
SN - 19487193
N1 - Žádný z autorů nemá afiliaci k MU, nelze tedy výsledek přenášet do RIV.
KW - FFN246
KW - fluorescent false neurotransmitters
KW - serotonin
KW - 5-HT
KW - monoaminergic neurons
KW - imaging probe
UR - https://pubs.acs.org/doi/abs/10.1021/acschemneuro.7b00320
N2 - Ongoing efforts in our laboratories focus on design of optical reporters known as fluorescent false neurotransmitters (FFNs) that enable the visualization of uptake into, packaging within, and release from individual monoaminergic neurons and presynaptic sites in the brain. Here, we introduce the molecular probe FFN246 as an expansion of the FFN platform to the serotonergic system. Combining the acridone fluorophore with the ethylamine recognition element of serotonin, we identified FFN54 and FFN246 as substrates for both the serotonin transporter and the vesicular monoamine transporter 2 (VMAT2). A systematic structure-activity study revealed the basic structural chemotype of aminoalkyl acridones required for serotonin transporter (SERT) activity and enabled lowering the background labeling of these probes while maintaining SERT activity, which proved essential for obtaining sufficient signal in the brain tissue (FFN246). We demonstrate the utility of FFN246 for direct examination of SERT activity and SERT inhibitors in 96-well cell culture assays, as well as specific labeling of serotonergic neurons of the dorsal raphe nucleus in the living tissue of acute mouse brain slices. While we found only minor FFN246 accumulation in serotonergic axons in murine brain tissue, FFN246 effectively traces serotonin uptake and packaging in the soma of serotonergic neurons with improved photophysical properties and loading parameters compared to known serotonin-based fluorescent tracers.
ER -
HENKE, Adam, Yekaterina KOVALYOVA, Matthew DUNN, Dominik DREIER, Niko G. GUBERNATOR, Iva DINCHEVA, Christopher HWU, Peter ŠEBEJ, Mark S. ANSORGE, David SULZER a Dalibor SAMEŠ. Toward Serotonin Fluorescent False Neurotransmitters: Development of Fluorescent Dual Serotonin and Vesicular Monoamine Transporter Substrates for Visualizing Serotonin Neurons. \textit{ACS CHEMICAL NEUROSCIENCE}. WASHINGTON: AMER CHEMICAL SOC, roč.~9, č.~5, s.~925-934, 19 s. ISSN~1948-7193. doi:10.1021/acschemneuro.7b00320. 2018.
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