Table 1.
History of GPCR deorphanizations
| 1986 | GPCRs share sequence similarities; orphan GPCRs can be found by homology |
| 1987 | Report of the first reported orphan GPCR: G-21 |
| 1988 | The first deorphanizations: G-21 as the 5-HT1A receptor and RGB-2 as the dopamine D2 receptor |
| 1989 | Introduction of the PCR-based screening approach for the discovery of orphan GPCRs |
| 1995 | The first novel transmitter as target of an orphan GPCR: orphanin FQ/nociceptin |
| 1990–present | Deorphanized GPCRs |
| Adenosine A1, A2A, A2B, A3 | |
| Adenosine diphosphate | |
| Adrenergic α1A, α1D, α2B, α2C, β1, β3 | |
| Adrenomedullin | |
| Anaphylatoxin C3a, C5a | |
| β-alanine, Angiotensin AT1b | |
| D-amino acids | |
| Apelin, basic L-α amino acids | |
| N-arachidonylglycine | |
| Bile acids | |
| Bradykinin | |
| Bombesin BB1, BB3 | |
| Bovine adrenal medulla peptide 22 | |
| Cannabinoid CB1, CB2 | |
| Calcitonin gene related peptide | |
| Chemokine CCR1, CCR2, CCR3, CCR4, CCR5, CXCR2, CXCR3, CXCR4 | |
| Cholecystokinin CCKa | |
| Cortistatin | |
| Dopamine D1, D2, D3, D4, D5 | |
| Eskine | |
| Estrogen | |
| 5-oxo-ETE | |
| Farnesyl pyrophosphate | |
| Follicle-stimulating hormone | |
| Formyl-peptide FPR2 | |
| Galanin type 2 | |
| Ghrelin | |
| Gonadotropin-releasing hormone | |
| Histamine H2, H3 | |
| α-ketoglutarate | |
| Kynurenic acid | |
| Kisspeptin/metastin | |
| Lactate | |
| Latrotoxin | |
| L-DOPA | |
| Leukotriene B4,C4,D4 | |
| Lysophosphatidic acid | |
| Lysophosphatidylcholine | |
| Lysophosphatidylinositol | |
| Medium- and long-chain fatty acids | |
| Melanin-concentrating hormone | |
| Melanocortin MC1, MC2, MC3, MC4, MC5 | |
| Melatonin MT1, MT2 | |
| 3- and 4-methyl-valeric acid | |
| Motilin | |
| Muscarinic acetylcholine M3, M4, M5 | |
| Neurokinin NK1, NK3 | |
| Neuromedin S, U | |
| Neuropeptides B/W | |
| Neuropeptide FF, AF | |
| Neuropeptide S | |
| Neuropeptide YY1, YY1-like, YY4 | |
| Neurotensin NTR2 | |
| Nicotinic acid | |
| Oleoylethanolamide | |
| Opioid κ, μ | |
| Orexins/hypocretins | |
| Orphanin FQ/nociceptin | |
| Oxysterols | |
| D-phenylalanine | |
| Prokineticins 1/2 | |
| Prolactin-releasing peptide | |
| Prostaglandin DP1, DP2 | |
| Prostanoid EP1, EP2, EP3, EP4, FP, IP1, TP | |
| Protease-activated 2,3 | |
| Proton | |
| Purinoceptor P2Y1, P2Y3, P2Y4, P2Y6, P2Y8 | |
| Psychosine | |
| RFamide-related protein 1,3 | |
| Pyroglutamylated arginine-phenylalanineamide peptide | |
| R-spondins | |
| Relaxin-1, -2, -3 | |
| Serotonin 5-HT1A, 5-HT1B, 5-HT1D, 5-HT1E, 5-HT1F, 5-HT2A, 5-HT2B, 5-HT4, 5-HT5A, 5-HT5B, 5-HT6, 5-HT7 | |
| Sphingosine 1-phosphate | |
| Sphingosylphosphorylcholine | |
| Somatostatin SST1, SST2, SST3, SST4, SST5 | |
| Succinate | |
| Trace amines | |
| Thyrotropin-stimulating hormone | |
| UDP-glucose | |
| Unsaturated long-chain free fatty acids | |
| Uracil nucleotide/cysteinyl leukotrienes | |
| Urotensin II | |
| Vasopressin V1b, V2 | |
| Zn2+ | |
Derived from Reference 14.
Abbreviation: GPCR, G protein–coupled receptor; PCR, polymerase chain reaction.