PMID- 20540519
OWN - NLM
STAT- MEDLINE
DCOM- 20101001
LR  - 20240511
IS  - 1520-5126 (Electronic)
IS  - 0002-7863 (Print)
IS  - 0002-7863 (Linking)
VI  - 132
IP  - 26
DP  - 2010 Jul 7
TI  - Development of pH-responsive fluorescent false neurotransmitters.
PG  - 8828-30
LID - 10.1021/ja101740k [doi]
AB  - We introduce pH-responsive fluorescent false neurotransmitters (pH-responsive 
      FFNs) as novel probes that act as vesicular monoamine transporter (VMAT) 
      substrates and ratiometric fluorescent pH sensors. The development of these 
      agents was achieved by systematic molecular design that integrated several 
      structural elements, including the aminoethyl group (VMAT recognition), 
      halogenated hydroxy-coumarin core (ratiometric optical pH sensing in the desired 
      pH range), and N- or C-alkylation (modulation of lipophilicity). Of 14 compounds 
      that were synthesized, the probe Mini202 was selected based on the highest uptake 
      in VMAT2-transfected HEK cells and desirable optical properties. Using Mini202, 
      we measured the pH of catecholamine secretory vesicles in PC-12 cells (pH 
      approximately 5.9) via two-photon fluorescence microscopy. Incubation with 
      methamphetamine led to an increase in vesicular pH (pH approximately 6.4), 
      consistent with a proposed mechanism of action of this psychostimulant, and 
      eventually to redistribution of vesicular content (including Mini202) from 
      vesicles to cytoplasm. Mini202 is sufficiently bright, photostable, and suitable 
      for two-photon microscopy. This probe will enable fundamental neuroscience and 
      neuroendocrine research as well as drug screening efforts.
FAU - Lee, Minhee
AU  - Lee M
AD  - Department of Chemistry, Columbia University, 3000 Broadway, New York, New York 
      10027, USA.
FAU - Gubernator, Niko G
AU  - Gubernator NG
FAU - Sulzer, David
AU  - Sulzer D
FAU - Sames, Dalibor
AU  - Sames D
LA  - eng
GR  - P01 DA010154/DA/NIDA NIH HHS/United States
GR  - P01 DA010154-150007/DA/NIDA NIH HHS/United States
GR  - R01 AA019801/AA/NIAAA NIH HHS/United States
GR  - R01 DA007418-18/DA/NIDA NIH HHS/United States
GR  - R01 DA007418/DA/NIDA NIH HHS/United States
PT  - Journal Article
PT  - Research Support, N.I.H., Extramural
PT  - Research Support, Non-U.S. Gov't
PL  - United States
TA  - J Am Chem Soc
JT  - Journal of the American Chemical Society
JID - 7503056
RN  - 0 (Catecholamines)
RN  - 0 (Fluorescent Dyes)
RN  - 0 (Neurotransmitter Agents)
SB  - IM
MH  - Animals
MH  - Catecholamines/metabolism
MH  - *Drug Discovery
MH  - Fluorescent Dyes/chemical synthesis/*chemistry/*metabolism
MH  - Hydrogen-Ion Concentration
MH  - Neurotransmitter Agents/*metabolism
MH  - Optical Phenomena
MH  - PC12 Cells
MH  - Rats
MH  - Secretory Vesicles/metabolism
MH  - Spectrometry, Fluorescence
PMC - PMC2923472
MID - NIHMS213654
EDAT- 2010/06/15 06:00
MHDA- 2010/10/05 06:00
PMCR- 2011/07/07
CRDT- 2010/06/15 06:00
PHST- 2010/06/15 06:00 [entrez]
PHST- 2010/06/15 06:00 [pubmed]
PHST- 2010/10/05 06:00 [medline]
PHST- 2011/07/07 00:00 [pmc-release]
AID - 10.1021/ja101740k [doi]
PST - ppublish
SO  - J Am Chem Soc. 2010 Jul 7;132(26):8828-30. doi: 10.1021/ja101740k.