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Characterization of G Protein-coupled Receptors by a Fluorescence-based Calcium Mobilization Assay
Published on: July 28, 2014
G protein-coupled receptor deorphanizations
Olivier Civelli1, Rainer K Reinscheid, Yan Zhang
1Department of Pharmacology, University of California, Irvine, Irvine, California 92617, USA. ocivelli@uci.edu
Annual Review of Pharmacology and Toxicology
|October 2, 2012
Summary
Discovering ligands for orphan G protein-coupled receptors (GPCRs) through reverse pharmacology is crucial. This review details the current status, successes, and challenges in deorphanizing these important cellular signaling proteins.
Area of Science:
- Molecular Biology
- Pharmacology
- Cellular Signaling
Background:
- G protein-coupled receptors (GPCRs) mediate intercellular communication via natural ligands.
- Modern molecular biology identifies most GPCRs before their natural ligands, classifying them as orphan GPCRs.
- The field of reverse pharmacology emerged to identify ligands for these orphan receptors.
Purpose of the Study:
- To review the current state of GPCR deorphanization.
- To provide examples of successful and surprising ligand discoveries.
- To highlight the challenges in identifying ligands for orphan GPCRs.
Main Methods:
- Literature review of GPCR deorphanization efforts.
- Analysis of case studies in reverse pharmacology.
- Discussion of methodologies employed in ligand discovery for orphan receptors.
Main Results:
- GPCR deorphanization is an active and evolving field.
- Several orphan GPCRs have been successfully deorphanized, revealing novel biological functions.
- Significant challenges remain, including technical hurdles and the sheer number of orphan receptors.
Conclusions:
- Reverse pharmacology is a vital approach for understanding GPCR function.
- Continued efforts in deorphanization are essential for advancing drug discovery and understanding cellular processes.
- Overcoming existing challenges will accelerate the identification of novel therapeutic targets.
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