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Anatomical profiling of G protein-coupled receptor expression
Jean B Regard1, Isaac T Sato, Shaun R Coughlin
1Cardiovascular Research Institute, University of California, San Francisco, San Francisco, CA 94158, USA. regardj@mail.nih.gov
Cell
|November 6, 2008
Summary
This study maps G protein-coupled receptors (GPCRs) across mouse tissues, revealing new functions and potential drug side effects. Understanding GPCRs in vivo aids in identifying therapeutic targets.
Area of Science:
- Molecular Biology
- Physiology
- Pharmacology
Background:
- G protein-coupled receptors (GPCRs) are crucial transmembrane signaling molecules involved in numerous physiological and disease processes.
- Understanding GPCR functions in vivo is essential for advancing biomedical research and drug development.
Purpose of the Study:
- To comprehensively map the transcript levels of 353 non-olfactory GPCRs across 41 adult mouse tissues.
- To identify novel functions and predict potential roles for understudied GPCRs.
- To explore the utility of GPCR expression analysis for predicting drug side effects.
Main Methods:
- Quantitative analysis of GPCR transcript levels in 41 adult mouse tissues.
- Application of cluster analysis to group GPCRs based on expression patterns.
- Experimental validation of predicted GPCR functions, including Gpr91's role in lipolysis.
Main Results:
- Cluster analysis revealed anticipated anatomical and functional groupings for many GPCRs.
- Identified previously unknown roles for several less-studied GPCRs, such as Gpr91's regulation of lipolysis in white adipose tissue.
- Demonstrated that pairwise GPCR expression analysis can predict potential drug side effects.
Conclusions:
- This study provides a valuable resource for in vivo GPCR research.
- The findings suggest that signaling intermediates like succinate may play roles in energy homeostasis.
- GPCR expression profiling offers a promising approach for predicting drug toxicity and identifying new therapeutic targets.
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