title: Development of Anionically Decorated Caged Neurotransmitters: In Vitro Comparison of 7-Nitroindolinyl- and 2-(p-Phenyl-o-nitrophenyl)propyl-Based Photochemical Probes.
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.
authors.affiliation: Department of Neuroscience, Mount Sinai School of Medicine, New York, NY, 10029, USA) graham.davies at mssm.edu.|Organic Chemistry Division II (CPC Division), CSIR-Indian Institute of Chemical Technology, Hyderabad, 500 007, India.
authors.forename: Srinivas
authors.initials: S
authors.lastname: Kantevari
authors.affiliation: Department of Neuroscience, Mount Sinai School of Medicine, New York, NY, 10029, USA) graham.davies at mssm.edu.
authors.forename: Stefan
authors.initials: S
authors.lastname: Passlick
authors.affiliation: Department of Neurobiology, Howard Hughes Medical Institute, Harvard Medical School, Cambridge, MA, 02115, USA.|Max Planck Florida Institute for Neuroscience, Jupiter, FL, 33458, USA.
authors.forename: Hyung-Bae
authors.initials: HB
authors.lastname: Kwon
authors.affiliation: Department of Neuroscience, Mount Sinai School of Medicine, New York, NY, 10029, USA) graham.davies at mssm.edu.
authors.forename: Matthew T
authors.initials: MT
authors.lastname: Richers
authors.affiliation: Department of Neurobiology, Howard Hughes Medical Institute, Harvard Medical School, Cambridge, MA, 02115, USA.
authors.forename: Bernardo L
authors.initials: BL
authors.lastname: Sabatini
authors.affiliation: Department of Neuroscience, Mount Sinai School of Medicine, New York, NY, 10029, USA) graham.davies at mssm.edu.
authors.forename: Graham C R
authors.initials: GC
authors.lastname: Ellis-Davies
mesh_terms: D000838:Anions; D001713:Biphenyl Compounds / Q000138:chemical synthesis / Q000737:chemistry* / Q000378:metabolism; D058787:GABA-A Receptor Antagonists / Q000737:chemistry / Q000378:metabolism; D005971:Glutamates / Q000138:chemical synthesis / Q000737:chemistry* / Q000378:metabolism; D007211:Indoles / Q000138:chemical synthesis / Q000737:chemistry* / Q000378:metabolism; D008027:Light; D008856:Microscopy, Fluorescence; D018377:Neurotransmitter Agents / Q000737:chemistry* / Q000378:metabolism; D010782:Photolysis / Q000187:drug effects; D011963:Receptors, GABA-A / Q000737:chemistry / Q000378:metabolism
chemical_list: C488057:2-amino-5-(5-((methoxycarbonyl)methyl)-7-nitroindol-1-yl)-5-oxopentanoic acid; D000838:Anions; D001713:Biphenyl Compounds; D058787:GABA-A Receptor Antagonists; D005971:Glutamates; D007211:Indoles; D018377:Neurotransmitter Agents; D011963:Receptors, GABA-A; C000616261:dcPNPP-Glu
keywords: GABA receptors; caged glutamate; neurotransmitters; photolysis; two-photon photolysis