Development of Anionically Decorated Caged Neurotransmitters: In Vitro Comparison of 7-Nitroindolinyl- and 2-(p-Phenyl-o-nitrophenyl)propyl-Based Photochemical Probes

Srinivas Kantevari, Stefan Passlick, Hyungbae Kwon, Matthew T. Richers, Bernardo L. Sabatini, Graham C.R. Ellis-Davies

Research output: Contribution to journalArticle

Abstract

Neurotransmitter uncaging, especially that of glutamate, has been used to study synaptic function for over 30 years. One limitation of caged glutamate probes is the blockade of γ-aminobutyric acid (GABA)-A receptor function. This problem comes to the fore when the probes are applied at the high concentrations required for effective two-photon photolysis. To mitigate such problems one could improve the photochemical properties of caging chromophores and/or remove receptor blockade. We show that addition of a dicarboxylate unit to the widely used 4-methoxy-7-nitroindolinyl-Glu (MNI-Glu) system reduced the off-target effects by about 50-70 %. When the same strategy was applied to an electron-rich 2-(p-Phenyl-o-nitrophenyl)propyl (PNPP) caging group, the pharmacological improvements were not as significant as in the MNI case. Finally, we used very extensive biological testing of the PNPP-caged Glu (more than 250 uncaging currents at single dendritic spines) to show that nitro-biphenyl caging chromophores have two-photon uncaging efficacies similar to that of MNI-Glu.

Original languageEnglish (US)
Pages (from-to)953-961
Number of pages9
JournalChemBioChem
Volume17
Issue number10
DOIs
StatePublished - May 17 2016
Externally publishedYes

Fingerprint

Chromophores
Photons
Neurotransmitter Agents
Glutamic Acid
Aminobutyrates
Dendritic Spines
Photolysis
GABA-A Receptors
Pharmacology
Electrons
Testing
In Vitro Techniques
diphenyl

Keywords

  • caged glutamate
  • GABA receptors
  • neurotransmitters
  • photolysis
  • two-photon photolysis

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Medicine
  • Molecular Biology
  • Organic Chemistry

Cite this

Development of Anionically Decorated Caged Neurotransmitters : In Vitro Comparison of 7-Nitroindolinyl- and 2-(p-Phenyl-o-nitrophenyl)propyl-Based Photochemical Probes. / Kantevari, Srinivas; Passlick, Stefan; Kwon, Hyungbae; Richers, Matthew T.; Sabatini, Bernardo L.; Ellis-Davies, Graham C.R.

In: ChemBioChem, Vol. 17, No. 10, 17.05.2016, p. 953-961.

Research output: Contribution to journalArticle

Kantevari, Srinivas ; Passlick, Stefan ; Kwon, Hyungbae ; Richers, Matthew T. ; Sabatini, Bernardo L. ; Ellis-Davies, Graham C.R. / Development of Anionically Decorated Caged Neurotransmitters : In Vitro Comparison of 7-Nitroindolinyl- and 2-(p-Phenyl-o-nitrophenyl)propyl-Based Photochemical Probes. In: ChemBioChem. 2016 ; Vol. 17, No. 10. pp. 953-961.
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