FASEB J.
HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS
QUICK SEARCH:   [advanced]


     

Published as doi: 10.1096/fj.07-9597com.
 (The FASEB Journal. 2007;21:3819-3826.)
© 2007 FASEB
This Article
Right arrow Full Text
Right arrow Full Text (PDF)
Right arrow All Versions of this Article:
fj.07-9597comv1
21/14/3819    most recent
Right arrow Alert me when this article is cited
Right arrow Alert me if a correction is posted
Services
Right arrow Email this article to a friend
Right arrow Similar articles in this journal
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Download to citation manager
Right arrow reprints & permissions
Citing Articles
Right arrow Citing Articles via HighWire
Right arrow Citing Articles via Google Scholar
Google Scholar
Right arrow Articles by von Degenfeld, G.
Right arrow Articles by Blau, H. M.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by von Degenfeld, G.
Right arrow Articles by Blau, H. M.

A universal technology for monitoring G-protein-coupled receptor activation in vitro and noninvasively in live animals

Georges von Degenfeld1,2, Tom S. Wehrman1,3, Mark M. Hammer and Helen M. Blau4

Baxter Laboratory in Genetic Pharmacology, Department of Microbiology and Immunology, Stanford University School of Medicine, Stanford, California, USA

4Correspondence: Baxter Laboratory, CCSR 4415, 269 Campus Dr., Stanford, CA 94305-5175, USA; E-mail: hblau{at}stanford.edu

G-protein coupled receptors (GPCRs) are a versatile and ubiquitous family of membrane receptors that transmit extracellular signals to mammalian cells and constitute the most important class of drug targets. Yet, sensitive and specific methods are lacking that would allow quantitative comparisons of pharmacologic properties of these receptors in physiological or pathological settings in live animals. We sought to overcome these limitations by employing low affinity, reversible β-galactosidase complementation to quantify GPCR activation via interaction with β-arrestin. A panel of cell lines was engineered expressing different GPCRs together with the reporter system. In vitro evaluation revealed highly sensitive, dynamic, and specific assessment of GPCR agonists and antagonists. Following implantation of the cells into mice, it was possible for the first time to monitor pharmacological GPCR activation and inhibition in their physiological context by noninvasive bioluminescence imaging in living animals. This technology has unique advantages that enable novel applications in the functional investigation of GPCR modulation in live animals in biological research and drug discovery.—von Degenfeld, G., Wehrman, T. S., Hammer, M. M., Blau, H. M. A universal technology for monitoring G-protein-coupled receptor activation in vitro and noninvasively in live animals.


Key Words: luminescent in vivo imaging • in vivo pharmacology • GPCRs




This article has been cited by other articles:


Home page
 J Biomol ScreenHome page
X. Zhao, A. Jones, K. R. Olson, K. Peng, T. Wehrman, A. Park, R. Mallari, D. Nebalasca, S. W. Young, and S.-H. Xiao
A Homogeneous Enzyme Fragment Complementation-Based {beta}-Arrestin Translocation Assay for High-Throughput Screening of G-Protein-Coupled Receptors
J Biomol Screen, September 1, 2008; 13(8): 737 - 747.
[Abstract] [PDF]


HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS
Copyright © 2007 by The Federation of American Societies for Experimental Biology.