1 research outputs found
Microscopic Visualization of Metabotropic Glutamate Receptors on the Surface of Living Cells Using Bifunctional Magnetic Resonance Imaging Probes
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 (mGluR<sub>5</sub>) antagonists. In order to directly visualize
mGluR<sub>5</sub> 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 <i>in
cellulo</i>. 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 mGluR<sub>5</sub> cell surface receptors was demonstrated
with the aid of their fluorescently labeled avidin conjugates, using
both total internal reflection fluorescence (TIRF) and confocal microscopy