Deorphanization of G-Protein-Coupled Receptors

Conference paper
Part of the Ernst Schering Foundation Symposium Proceedings book series (SCHERING FOUND, volume 2006/2)


G-protein-coupled receptors constitute one of the major families of drug targets. Orphan receptors, for which the ligands and function are still unknown, are an attractive set of future targets for presently unmet medical needs. Screening strategies have been developed over the years in order to identify the natural ligands of these receptors. Natural or chimeric G-proteins that can redirect the natural coupling of receptors toward intracellular calcium release are frequently used. Potential problems include poor expression or trafficking to the cell surface, constitutive activity of the receptors, or the presence of endogenous receptors in the cell types used for functional expression, leading to nonspecific responses. Many orphan receptors characterized over the last 10 years have been associated with previously known bioactive molecules. However, new and unpredicted biological mediators have also been purified from complex biological sources. A few old and recent examples, including nociceptin, chemerin, and the F2L peptide are illustrated. Future challenges for the functional characterization of the remaining orphan receptors include the potential requirement of specific proteins necessary for quality control, trafficking or coupling of specific receptors, the possible formation of obligate heterodimers, and the possibility that some constitutively active receptors may lack ligands or respond only to inverse agonists. Adapted expression and screening strategies will be needed to deal with these issues.


Olfactory Receptor Opiate Receptor Orphan Receptor Formyl Peptide Receptor Endogenous Opioid Peptide 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.



The research conducted in the authors' laboratory was supported by the Actions de Recherche Concertées of the Communauté Française de Belgique, the French Agence Nationale de Recherche sur le SIDA, the Belgian programme on Interuniversity Poles of attraction initiated by the Belgian State, Prime Minister's Office, Science Policy Programming, the European Union (grants LSHB-CT-2003–503337/GPCRs and LSHB-CT-2005–518167/INNOCHEM), the Fonds de la Recherche Scientifique Médicale of Belgium, and the Fondation Médicale Reine Elisabeth. The scientific responsibility is assumed by the authors.


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Copyright information

© Springer-Verlag 2007

Authors and Affiliations

  1. 1.IRIBHNULB Campus ErasmeBruxellesBelgium
  2. 2.Euroscreen S.AGosseliesBelgium

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