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• W2414842006 abstract "Radioligand binding is widely used to characterize receptors and to determine their anatomical distribution, particularly the superfamily of rhodopsinlike, seven-transmembrane-spanning G protein-coupled receptors (GPCRs). More than 200 receptors that transduce many important physiological processes and are the target for about 50% of all drugs have been identified in this family (, , , , , ) . A further approx 160 or so ″orphan″ GPCRs have been predicted to exist from the human genome and have mRNA sequences characteristic of 7TM GPCRs, but their endogenous ligands await identification. Most of these receptors have been artificially expressed in cell lines linked to a reporter sys- tem to identify when a ligand binds to the receptor (see Chapter 2). This ″re- verse pharmacology″ approach continues to be used to screen compounds from existing or new combinatorial libraries of biologically active molecules, and has been very successful. More than 45 receptors have been ″de-orphanized″ or paired with their cognate ligand, with nearly half of these putative endo- genous transmitters turning out to be peptides (see Table 1). The number of pairings continues to increase. It is estimated that about 70 of the remaining orphan receptors could turn out to have a peptidic ligand (). Table 1 Orphan Receptors Recently Paired With Their Cognate Peptidic Ligands Year Human peptide Orphan receptor Ligand source 1995 Nociceptin/Orphanin FQ ORL-1/OFQ Porcine brain 1998 Apelin Apelin/APJ Bovine stomach Orexin A and B (hypercretin 1+2) Orexin 1 and 2 Rat brain Prolactin Releasing Peptide (PRrP) hGRP-3/GPR10 Bovine hypothalamus 1999 Ghrelin (motilin related peptide) Ghrelin/GHS-R Rat stomach Melanin concentrating hormone (MCH) MCHR1 Rat whole brain Motilin GPR38 Peptide library Tuberoinfundibular peptide 39 (TIP39) PTH2R Bovine hypothalamus Urotensin-II UT/GPR14/SENR Peptide library 2000 Neuromedin U-25 (NMU25) FM3 and FM4 Peptide library Neuropeptides FF and AF NPFF-R1 Bovine brain 2001 Metastin (Kisspeptin-54) GPR54 Human placenta MCH MCHR2 Peptide library Urocortin II and I (stresscopins) CRF2 Peptide library 2002 Relaxin LGR7 and LGR8 Peptide library Bovine adrenomedullary peptide 22 (BAM-22) SNSR3 and SNSR4 Peptide library Neuropeptides B and W GPR7 and GPR8 Peptide library 2003 QRFP43 (P52) SP9155/GPR103 Genome database Relaxin-3/INSL7 GPR135/SALPR Porcine brain See refs. 2 and 3 for further information and citations to original papers." @default.
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• W2414842006 date "2005-05-02" @default.
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• W2414842006 title "Radioligand-Binding and Molecular-Imaging Techniques for the Quantitative Analysis of Established and Emerging Orphan Receptor Systems" @default.
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• W2414842006 doi "https://doi.org/10.1385/1-59259-927-3:093" @default.
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