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Microscopic visualisation of metabotropic glutamate receptors on the surface of living cells using bifunctional magnetic resonance imaging probes

Mishra, Anurag; Mishra, Rita; Gottschalk, Sven; Pal, Robert; Sim, Neil; Engelmann, Joern; Goldberg, Martin; Parker, David

Microscopic visualisation of metabotropic glutamate receptors on the surface of living cells using bifunctional magnetic resonance imaging probes Thumbnail


Authors

Anurag Mishra

Rita Mishra

Sven Gottschalk

Neil Sim

Joern Engelmann



Abstract

A series of bimodal metabotropic glutamate-receptor targeted MRI contrast agents has been developed and evaluated, based on established competitive metabotropic Glu receptor subtype 5 (mGluR5) antagonists. In order to directly visualize mGluR5 binding of these agents on the surface of live astrocytes, variations in the core structure were made. A set of gadolinium conjugates containing either a cyanine dye or a fluorescein moiety was accordingly prepared, to allow visualization by optical microscopy in cellulo. In each case, surface receptor binding was compromised and cell internalization observed. Another approach, examining the location of a terbium analogue via sensitized emission, also exhibited nonspecific cell uptake in neuronal cell line models. Finally, biotin derivatives of two lead compounds were prepared, and the specificity of binding to the mGluR5 cell surface receptors was demonstrated with the aid of their fluorescently labeled avidin conjugates, using both total internal reflection fluorescence (TIRF) and confocal microscopy.

Citation

Mishra, A., Mishra, R., Gottschalk, S., Pal, R., Sim, N., Engelmann, J., …Parker, D. (2014). Microscopic visualisation of metabotropic glutamate receptors on the surface of living cells using bifunctional magnetic resonance imaging probes

Other Type Other
Online Publication Date Nov 19, 2013
Publication Date Feb 19, 2014
Deposit Date Jun 19, 2014
Publicly Available Date Mar 29, 2024
Pages 128-137
DOI https://doi.org/10.1021/cn400175m
Keywords mGluR5, Imaging agents, Lanthanides, MRI, Microscopy.
Additional Information URL of output: https://doi.org/10.1021/cn400175m
Volume: 5
Issue: 2
ISSN or ISBN: 1948-7193

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Copyright Statement
This document is the Accepted Manuscript version of a Published Work that appeared in final form in ACS Chemical Neuroscience, copyright © American Chemical Society after peer review and technical editing by the publisher. To access the final edited and published work see http://pubs.acs.org/doi/abs/10.1021/cn400175m.





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