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• W2768455295 abstract "Neuropeptides are the largest class of intercellular signaling molecules, contributing to a wide variety of physiological processes. Neuropeptide receptors are therapeutic targets for a broad range of drugs, including medications to treat pain, addiction, sleep disorders, and nausea. In addition to >100 peptides with known functions, many peptides have been identified in mammalian brain for which the cognate receptors have not been identified. Similarly, dozens of orphan G protein-coupled receptors have been identified in the mammalian genome. While it would seem straightforward to match the orphan peptides and receptors, this is not always easily accomplished. In this review we focus on peptides named PEN and big LEN, which are among the most abundant neuropeptides in mouse brain, and their recently identified receptors: GPR83 and GPR171. These receptors are co-expressed in some brain regions and are able to interact. Because PEN and big LEN are produced from the same precursor protein and co-secreted, the interaction of GPR83 and GPR171 is physiologically relevant. In addition to interactions of these two peptides/receptors, PEN and LEN are co-localized with neuropeptide Y and Agouti-related peptide in neurons that regulate feeding. In this review, using these peptide receptors as an example, we highlight the multiple modes of regulation of receptors and present the emerging view that neuropeptides function combinatorially to generate a network of signaling messages. The complexity of neuropeptides, receptors, and their signaling pathways is important to consider both in the initial deorphanization of peptides and receptors, and in the subsequent development of therapeutic applications." @default.
• W2768455295 created "2017-12-04" @default.
• W2768455295 creator A5053630827 @default.
• W2768455295 creator A5082020452 @default.
• W2768455295 date "2018-05-01" @default.
• W2768455295 modified "2023-10-12" @default.
• W2768455295 title "Orphan neuropeptides and receptors: Novel therapeutic targets" @default.
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• W2768455295 doi "https://doi.org/10.1016/j.pharmthera.2017.11.006" @default.
• W2768455295 hasPubMedCentralId "https://www.ncbi.nlm.nih.gov/pmc/articles/5899030" @default.
• W2768455295 hasPubMedId "https://pubmed.ncbi.nlm.nih.gov/29174650" @default.
• W2768455295 hasPublicationYear "2018" @default.
• W2768455295 type Work @default.

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