Journal
BRITISH JOURNAL OF PHARMACOLOGY
Volume 153, Issue -, Pages S339-S346Publisher
NATURE PUBLISHING GROUP
DOI: 10.1038/sj.bjp.0707606
Keywords
orphan GPCR; reverse pharmacology; neuropeptides; orexins; MCH; ghrelin; transmitters
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Funding
- NIDDK NIH HHS [DK70619, R01 DK070619, R01 DK063001, DK63001] Funding Source: Medline
- NIMH NIH HHS [MH60231, R01 MH060231] Funding Source: Medline
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Orphan G protein-coupled receptors (GPCRs) are receptors lacking endogenous ligands. Found by molecular biological analyses, they became the roots of reverse pharmacology, in which receptors are attempted to be matched to potential transmitters. Later, when high-throughput screening technology was applied to reverse pharmacology, dozens of orphan GPCRs became deorphanized. Furthermore, novel neuropeptides were discovered. This review retraces the history of the orphan GPCRs and of the discoveries of their endogenous ligands, it also discusses the difficulties that the search for new ligands is presently encountering.
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