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Methods Enzymol. 2012;514:33-44. doi: 10.1016/B978-0-12-381272-8.00002-7.

Orphan GPCRs and methods for identifying their ligands.

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Department of Biochemistry, National Cerebral and Cardiovascular Center Research Institute, Suita, Osaka, Japan.


G protein-coupled receptors (GPCRs) constitute the largest family of cell-surface receptors. These proteins play a crucial role in physiology by facilitating cell communication through recognition of diverse ligands, including bioactive peptides, amines, nucleosides, and lipids. The human genome sequencing project identified more than 100 orphan GPCRs, whose ligands had not yet been discovered. We subsequently identified ghrelin, neuromedin U, and neuromedin S as endogenous ligands of various orphan GPCRs and have proposed various mechanisms through which these peptides regulate physiological functions through their cognate GPCRs. In this chapter, we review methods for identifying novel peptide ligands of orphan GPCRs.

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