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Functional genomics: the search for novel neurotransmitters and neuropeptides
Author(s) -
Civelli Olivier
Publication year - 1998
Publication title -
febs letters
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.593
H-Index - 257
eISSN - 1873-3468
pISSN - 0014-5793
DOI - 10.1016/s0014-5793(98)00524-9
Subject(s) - g protein coupled receptor , nociceptin receptor , computational biology , orphan receptor , neuropeptide , biology , functional genomics , receptor , gene , genomics , neuroscience , genome , genetics , opioid peptide , opioid , transcription factor
Functional genomics can be defined as the search for the physiological role of a gene for which only its primary sequence is known. Most of the genes encoding proteins containing seven hydrophobic stretches code for G protein‐coupled receptors (GPCRs). Although many of these have been shown to interact with known natural ligands, several bind ligands which have not been thus far isolated. These are the so‐called orphan GPCRs. As an example of functional genomics, an `orphan receptor strategy' has been developed to identify the natural ligands of orphan GPCRs. The application of this strategy is bound to revolutionize our understanding of the diversity of the primary messengers which modulate synaptic transmission. This review discusses the basic concepts and some of the particular problems associated with the orphan receptor strategy. The strategy's potential is exemplified by its successes which culminated in the discovery of the neuropeptides `orphanin FQ/nociceptin' and `orexins/hypocretins'. The steps that led to the characterization of these neuropeptides are discussed as are some of the further studies that have addressed the roles of these neuropeptides. To conclude, some of the implications of the application of the orphan receptor strategy are discussed.