However, substantial evidence exists that TAARs are expressed in peripheral human tissues outside of the OE (11, 47). 3. The inhibition of myeloid leukemia cell proliferation is also mediated by a further OR, the isononylalcohol-activated OR51B5 (116). The receptors that actually bind with the molecules that we smell are called Olfactory receptor neurons. They pass their signal through the caribform plate, then down the olfactory nerve, and finally to the olfactory bulb in the brain. G protein-dependent agonism and antagonism of odorants, Sinding C, Kemper E, Spornraft-Ragaller P, Hummel T, Decreased perception of bourgeonal may be linked to male idiopathic infertility, Sondersorg AC, Busse D, Kyereme J, Rothermel M, Neufang G, Gisselmann G, Hatt H, Conrad H, Chemosensory information processing between keratinocytes and trigeminal neurons, Spehr J, Gelis L, Osterloh M, Oberland S, Hatt H, Spehr M, Neuhaus EM, G protein-coupled receptor signaling via Src kinase induces endogenous human transient receptor potential vanilloid type 6 (TRPV6) channel activation, Spehr M, Gisselmann G, Poplawski A, Riffell JA, Wetzel CH, Zimmer RK, Hatt H, Identification of a testicular odorant receptor mediating human sperm chemotaxis, Spehr M, Schwane K, Riffell JA, Barbour J, Zimmer RK, Neuhaus EM, Hatt H, Particulate adenylate cyclase plays a key role in human sperm olfactory receptor-mediated chemotaxis, Strünker T, Goodwin N, Brenker C, Kashikar ND, Weyand I, Seifert R, Kaupp UB, The CatSper channel mediates progesterone-induced Ca, Tomlins SA, Laxman B, Varambally S, Cao X, Yu J, Helgeson BE, Cao Q, Prensner JR, Rubin MA, Shah RB, Mehra R, Chinnaiyan AM, Role of the TMPRSS2-ERG gene fusion in prostate cancer, Triller A, Boulden EA, Churchill A, Hatt H, Englund J, Spehr M, Sell CS, Odorant-receptor interactions and odor percept: a chemical perspective, Tsai T, Veitinger S, Peek I, Busse D, Eckardt J, Vladimirova D, Jovancevic N, Wojcik S, Gisselmann G, Altmüller J, Ständer S, Luger T, Paus R, Cheret J, Hatt H, Two olfactory receptors-OR2A4/7 and OR51B5-differentially affect epidermal proliferation and differentiation, Uhlén M, Fagerberg L, Hallström BM, Lindskog C, Oksvold P, Mardinoglu A, Sivertsson Å, Kampf C, Sjöstedt E, Asplund A, Olsson I, Edlund K, Lundberg E, Navani S, Szigyarto CA-K, Odeberg J, Djureinovic D, Takanen JO, Hober S, Alm T, Edqvist P-H, Berling H, Tegel H, Mulder J, Rockberg J, Nilsson P, Schwenk JM, Hamsten M, von Feilitzen K, Forsberg M, Persson L, Johansson F, Zwahlen M, von Heijne G, Nielsen J, Pontén F, Molecular mechanism for ligand discrimination of cyclic nucleotide-gated channels, Veitinger T, Riffell JR, Veitinger S, Nascimento JM, Triller A, Chandsawangbhuwana C, Schwane K, Geerts A, Wunder F, Berns MW, Neuhaus EM, Zimmer RK, Spehr M, Hatt H, Vigushin DM, Poon GK, Boddy A, English J, Halbert GW, Pagonis C, Jarman M, Coombes RC; Cancer Research Campaign Phase I/II Clinical Trials Committee, Volz A, Ehlers A, Younger R, Forbes S, Trowsdale J, Schnorr D, Beck S, Ziegler A, Complex transcription and splicing of odorant receptor genes, Von Dannecker LE, Mercadante AF, Malnic B, Ric-8B, an olfactory putative GTP exchange factor, amplifies signal transduction through the olfactory-specific G-protein Galphaolf, Ric-8B promotes functional expression of odorant receptors, Wallrabenstein I, Kuklan J, Weber L, Zborala S, Werner M, Altmüller J, Becker C, Schmidt A, Hatt H, Hummel T, Gisselmann G, Human trace amine-associated receptor TAAR5 can be activated by trimethylamine, Wallrabenstein I, Singer M, Panten J, Hatt H, Gisselmann G, Timberol Inhibits TAAR5-Mediated Responses to Trimethylamine and Influences the Olfactory Threshold in Humans, Wang J, Weng J, Cai Y, Penland R, Liu M, Ittmann M, The prostate-specific G-protein coupled receptors PSGR and PSGR2 are prostate cancer biomarkers that are complementary to alpha-methylacyl-CoA racemase, Wasik AM, Millan MJ, Scanlan T, Barnes NM, Gordon J, Evidence for functional trace amine associated receptor-1 in normal and malignant B cells, Weber L, Al-Refae K, Ebbert J, Jägers P, Altmüller J, Becker C, Hahn S, Gisselmann G, Hatt H, Activation of odorant receptor in colorectal cancer cells leads to inhibition of cell proliferation and apoptosis, Weigle B, Fuessel S, Ebner R, Temme A, Schmitz M, Schwind S, Kiessling A, Rieger MA, Meye A, Bachmann M, Wirth MP, Rieber EP, D-GPCR: a novel putative G protein-coupled receptor overexpressed in prostate cancer and prostate, Wellerdieck C, Oles M, Pott L, Korsching S, Gisselmann G, Hatt H, Functional expression of odorant receptors of the zebrafish, Regulation of human prostate-specific G-protein coupled receptor, PSGR, by two distinct promoters and growth factors, Weng J, Wang J, Cai Y, Stafford LJ, Mitchell D, Ittmann M, Liu M, Increased expression of prostate-specific G-protein-coupled receptor in human prostate intraepithelial neoplasia and prostate cancers, Weng J, Wang J, Hu X, Wang F, Ittmann M, Liu M, PSGR2, a novel G-protein coupled receptor, is overexpressed in human prostate cancer, Wennemuth G, Westenbroek RE, Xu T, Hille B, Babcock DF, Wetzel CH, Oles M, Wellerdieck C, Kuczkowiak M, Gisselmann G, Hatt H, Specificity and sensitivity of a human olfactory receptor functionally expressed in human embryonic kidney 293 cells and, Weyand I, Godde M, Frings S, Weiner J, Müller F, Altenhofen W, Hatt H, Kaupp UB, Cloning and functional expression of a cyclic-nucleotide-gated channel from mammalian sperm, Wiese H, Gelis L, Wiese S, Reichenbach C, Jovancevic N, Osterloh M, Meyer HE, Neuhaus EM, Hatt HH, Radziwill G, Warscheid B, Quantitative phosphoproteomics reveals the protein tyrosine kinase Pyk2 as a central effector of olfactory receptor signaling in prostate cancer cells, Wolf S, Gelis L, Dörrich S, Hatt H, Kraft P, Evidence for a shape-based recognition of odorants in vivo in the human nose from an analysis of the molecular mechanism of lily-of-the-valley odorants detection in the Lilial and Bourgeonal family using the C/Si/Ge/Sn switch strategy, Wolf S, Jovancevic N, Gelis L, Pietsch S, Hatt H, Gerwert K, Dynamical Binding Modes Determine Agonistic and Antagonistic Ligand Effects in the Prostate-Specific G-Protein Coupled Receptor (PSGR), Wu C, Jia Y, Lee JH, Kim Y, Sekharan S, Batista VS, Lee S-J, Activation of OR1A1 suppresses PPAR-γ expression by inducing HES-1 in cultured hepatocytes, Xu L, Tang H, Chen DW, El-Naggar AK, Wei P, Sturgis EM, Genome-wide association study identifies common genetic variants associated with salivary gland carcinoma and its subtypes, Xu LL, Stackhouse BG, Florence K, Zhang W, Shanmugam N, Sesterhenn IA, Zou Z, Srikantan V, Augustus M, Roschke V, Carter K, McLeod DG, Moul JW, Soppett D, Srivastava S, PSGR, a novel prostate-specific gene with homology to a G protein-coupled receptor, is overexpressed in prostate cancer, Xu LL, Sun C, Petrovics G, Makarem M, Furusato B, Zhang W, Sesterhenn IA, McLeod DG, Sun L, Moul JW, Srivastava S, Quantitative expression profile of PSGR in prostate cancer, The sense of smell: genomics of vertebrate odorant receptors, Yuan TT, Toy P, McClary JA, Lin RJ, Miyamoto NG, Kretschmer PJ, Cloning and genetic characterization of an evolutionarily conserved human olfactory receptor that is differentially expressed across species, Further Consideration of the Association Between OR2W3 Mutation and Retinitis Pigmentosa, G protein-coupled receptors participate in cytokinesis, Zhao H, Ivic L, Otaki JM, Hashimoto M, Mikoshiba K, Firestein S, Functional expression of a mammalian odorant receptor, Zhao W, Ho L, Varghese M, Yemul S, Dams-O’Connor K, Gordon W, Knable L, Freire D, Haroutunian V, Pasinetti GM, Decreased level of olfactory receptors in blood cells following traumatic brain injury and potential association with tauopathy, Synergism of accessory factors in functional express ion of mammalian odorant receptors, https://doi.org/10.1152/physrev.00013.2017, Olfactory receptor 78 participates in carotid body response to a wide range of low O2 levels but not severe hypoxia, Clonal Heterogeneity Reflected by PI3K-AKT-mTOR Signaling in Human Acute Myeloid Leukemia Cells and Its Association with Adverse Prognosis, American Journal of Physiology-Cell Physiology, American Journal of Physiology-Endocrinology and Metabolism, American Journal of Physiology-Gastrointestinal and Liver Physiology, American Journal of Physiology-Heart and Circulatory Physiology, American Journal of Physiology-Lung Cellular and Molecular Physiology, American Journal of Physiology-Regulatory, Integrative and Comparative Physiology, American Journal of Physiology-Renal Physiology, American Journal of Physiology (1898-1976), PBMC-derived CD8+-T cells, PCa cell line PC-3 and LNCaP, PSGR peptide synthesis, RT-PCR cytokine ELISA, IFN-γ ELISPOT assay, cytotoxicity assay, PSGR-derived peptides as tumor-associated antigen recognized by CD8+-T cells, Peripheral blood mononuclear cells (PBMC), mouse primary cortico-hippocampal neurons, ORs as biomarkers for traumatic brain injury (decreased expression in PBMC) activation of overexpressed OR4M1 leads to reduced tau phosphorylation, Aorta, coronary artery, umbilical vein endothelial cells (HUVEC cell line), WB, calcium assay, migration assay, Matrigel plug assay, siRNA, Enhanced migration enhanced angiogenesis in vivo, Acute myeloid leukemia cells (K562 cell line), primary blood cells of acute myeloid leukemia patients, Sandalore, brahmanol antagonist: phenirat, RT-PCR, IF, calcium imaging (fura 2-AM), WB, cell proliferation assay, annexin-V/PI staining, Inhibited cell proliferation enhanced cell apoptosis, cell cycle arrest (G, Acute myeloid leukemia cells (K562 cell line), RT-PCR, IF, calcium imaging (fura 2-AM), WB, cell proliferation assay, Iso-dependent receptor downregulation inhibited cell proliferation, Stem cell-derived cardiomyocytes, human myocardial tissue culture, Nonanoic acid, decanoic acid, further MCFS, antagonist:2- ethylhexanoic acid, CRE-luciferase assay, calcium imaging (fura 2-AM), siRNA, RT-PCR, WB, IHC, contractile force measurements, Negative chronotropic and inotropic effects reduction of contraction force of explanted heart, EC cells (BON cell line), primary mucosal human EC cells (ileum), Thymol, geraniol (OR1G1) bourgeonal, helional (mouse orthologous of OR1A1, OR3A1), RT-PCR, calcium imaging (fluo 4-AM), serotonin enzyme immunoassay, amperome try, Primary EC cells, neoplastic EC cells (KRJ-I), qRT-PCR, microarray, ERK ELISA, flow cytometry Ca, Serotonin release, inhibited by somatostatin analog, RT-PCR, IF, calcium imaging (fluo 4-AM), cAMP/PKA assay, lipid analysis, siRNA, Reduced mitochondrial glycerol-3-phosphate acyltransferase (GPAM) gene expression involved in triglyceride synthesis, RT-PCR, IF, calcium imaging (fura 2-AM), cAMP assay, cell proliferation assay, propidium iodide staining, WB, siRNA, RT-PCR, IF, calcium imaging (fura 2-AM), WB, serotonin ELISA, Colorectal cancer cell line HCT116, colon cancer tissue, RNA-Seq, RT-PCR, IHC, CRE-luciferase assay, calcium imaging, WB, siRNA, proliferation assay, caspase-3/7 assay (apoptose), phalloidin staining (cytoskeleton), Inhibited cell proliferation and migration, promoted apoptosis, RT-PCR, IF, recombinant expression, calcium imaging, microcapillary bioassay, acrosome reaction assay, Chemotaxis (faster swim speed and flagellar beat rate), PCa cell lines LNCaP and PC-3, HEK293 cell line, primary prostate epithelial cells, β-Ionone, androstenone derivatives, antagonist: α-ionone, RT-PCR, IF, calcium imaging (fura 2-AM), patch clamp, WB, siRNA, cell proliferation assay, RT-PCR, recombinant expression, calcium imaging, cAMP ELISA, motility assay, microcapillary bioassay, acrosome reaction assay, Cervical epithelial cancer cell line HeLa, qRT-PCR, IF, siRNA, live cell imaging, flow cytometry, PSGR transgenic mouse model, in vivo, PCa cell lines LNCaP and MDA PCa2a, q-RT-PCR, IHC, WB, reportergen assay, xenograft, transgenic mice, Overexpression promotes inflammation and low-grade PIN in transgenic mice enhance d tumor development in LNCaP, Nested-PCR, cell invasion assay, xenograft (LNCaP), in vivo imaging and postmortem IHC, Promoted cell invasiveness in vitro metastasis spreading in vivo, Nerol (OR2W3), methional (OR2H1), dimetol (OR10J1), Odorant-dependent activation of ORs induces Ca, PCa tissue, PIN tissue, PCa cell lines LNCaP, PC3, and C4–2, IHC (tissue microarray), WB, cell invasion, MTT cell proliferation assay, Inhibited cell proliferation and promoted cell invasion (C4–2 high protein expression in PIN, low expression in advanced PCa, Advanced analysis of proteins involved in the signaling pathway, Benign prostatic tissue, PCa tissue, PCa metastases tissue, LNCaP cell line, NGS, qRT-PCR, WB, IHC, IF, MTT cell proliferation assay, crystal violet staining, SA-β-GAL staining, PSA assay, Inh ibited cell proliferation induction of cellular senescence interference with AR-mediated signaling, Kidney tissue, proximal tubule HK-2 cells cell line, Pulmonary neuroendocrine cells (PNECs), human tracheobronchial epithelial cells (hTECs), Bourgeonal, bergamot oil, citronellal, nonanal, hexadecanol, Decreased secretion of serotonin, release of neuropeptide CGRP, RT-PCR, IF, WB, IHC, calcium imaging (fura 2-AM), TUNNEL assay, live imaging microscopy, Inhibited cell proliferation, apoptosis and migration, Bourgeonal/undecanal (OR1D2), amylbutyrate (OR2AG1), RT-PCR, IF, IHC, calcium imaging (fura 2-AM), cAMP assay, WB, contraction assay, cytokine ELISA, OR2AG1: Inhibited histamine-induced contraction, OR1D2: Increase in cell contractility, secretion of IL-8 and GM-CSF, HaCaT cell line, mouse trigeminal neurons, Coculture, calcium imaging (fura 2-AM), patch clamp, ATP assay, propidium iodide staining, Odorant-induced communication between skin cells and trigeminal ganglia via ATP which is mediated by pannexins, Primary keratinocytes, HaCaT cell line, HEK293 cell line, Sandalore, brahmanol, antagonists: oxyphenylon, phenirat, Microarray, RT-PCR, IF, calcium imaging (fura 2-AM), cAMP Assay, WB, siRNA, propidium iodide staining, cell proliferation assay, migration assay, skin organ culture, Enhanced cell proliferation, migration and wound healing, qRT-PCR, IF, calcium imaging (fura 2-AM), cAMP assay, WB, caspase-3/7 assay, cell proliferation assay, melanin content assay, differentiation assay, Inhibited cell proliferation, enhanced melanogenesis and dendritogenesis, Primary keratinocytes, HaCaT cell line, HEK293, Cyclohexyl-salicylate (OR2A4), isononyl-alcohol (OR51B5), NGS, RT-PCR, IHC, IF, calcium imaging, IL ELISA, phospho kinase array, WB, caspase-3/7 assay, cell proliferation assay, skin organ culture, migration assay, siRNA, OR2A4/7: Influences cytokinesis, increased cell proliferation, IL-1 secretion secretion, OR51B5: Enhanced migration, regeneration of keratinocyte monolayers, IL-6 secretion, Primary melanoma cells derived from metastatic and vertical-growth phase, qRT-PCR, IF, calcium imaging (fura 2-AM), ISH, siRNA, cell proliferation assay, migration assay, Inhibited cell proliferation and migration, apoptosis. The olfactory neurons therefore produced only a fraction of all possible olfactory receptors, which decreased the ability of the mice to respond to odors. Thus ORs may significantly contribute to abnormal bowel functions, such as diarrhea or constipation. Furthermore, the composition of odorant blends is subjectively influenced by hedonic properties, as unpleasant odors are often reluctantly used by researchers within deorphanization experiments. Essential oils are mainly composed of volatile terpenes and terpenoids, as well as aromatic molecules (143). Several of these volatiles have been shown to activate ectopically expressed ORs and thus influence physiological processes in various human cells; several examples include β-ionone (roses and berries), citronellal (citrus species), citronellol (pelargonium), thymol (thyme), and geraniol (rose oil and citronella oil) (3, 17, 70, 112, 119, 132, 155, 159, 161, 203, 211). OR51E2 gene expression, for example, is controlled by different promoters in the OE and prostate (135). Involved cellular functions: proliferation, cell growth, differentiation, apoptosis, migration, and secretion (4, 17, 24, 49, 60, 82, 88, 115, 116, 118, 119, 132, 150, 158, 164, 173, 179, 182, 191, 209); senescence (118); dendritogenesis (60); chemotaxis (130, 173, 182); angiogenesis (93); wound healing (24); muscle contraction (82); hepatic metabolism (119); cytokinesis (179, 209); melanogenesis (60); and invasiveness (158). In this timely book, Warrick Brewer and his team of experts set out our current understanding of olfaction and mental health, relating it to broader principles of neural development and processing as a foundation for understanding ... Olfactory Receptor Localization and Function: An Emerging Role for GPCR Heterodimerization Chris Hague, Randy A. The human TAAR family comprises six gene members, of which four members have been identified at trace levels in the OE (27). We take advantage of the high frequency of natural OR knockouts in the human genome to tackle a major bottleneck in the field—namely, how an odor is transduced into perceptual characteristics. In addition to the participating OR and cellular systems, these processes are highly dependent on the odorant structure and concentration, the heterotrimeric G protein type or subunit, and the participation of other and/or less modulatory active scaffold proteins/cofactors, as well as the molecular features of the cellular system. Recently, the complete testicular and spermatozoal OR transcript repertoire has been demonstrated, highlighting the testes as the richest OR transcript-expressing tissue outside of the nose (47, 49). In contrast, human TAAR5 is more abundant in the human OE (135) and is also ectopically expressed at low levels in the human brain (47). Recent studies have indicated that OR51E2 also functions in human melanocyte homeostasis (60). The expression of this OR is virtually nondetectable in other tissues, including the human OE (49, 135). Olfactory cells are nerve cells, part of the nervous system and classified as part of the peripheral sensory nervous system. They are located in the scent-sensing organs of humans and other animals, have a specific shape that is dependent on their specific location, and vary greatly in their number and sensitivity. So separating the brain from the olfactory epithelium in this nasal passage over here is a piece of bone known as the cribriform plate. ScienceDaily, 8 February 2017. In contrast to myeloid leukemia cells, the sandalore-activated receptor OR2AT4 promotes human keratinocyte proliferation and migration, which results in accelerated cutaneous wound healing in an ex vivo system (24). Its mitral and tufted cells have connections to each other through small neurons within the olfactory bulb (interneurons) which transform the input from the ORNs. Atf5 Links Olfactory Receptor Induced Stress Response to Proper Neuronal Function Jerome Keoki Kahiapo Mammalian olfaction requires the enduring expression of a single olfactory receptor (OR) gene for the life of each sensory neuron. This work investigated how the functional variations in olfactory GPCRs (ORs)-the largest GPCR family-are encoded in the primary sequence. The expression pattern of ORs in a specific tissue is relatively stable; however, the number of ORs expressed in different human tissues varies substantially, ranging from only a few ORs in the liver or skeletal muscle to more than 60 ORs in the testis (47). Halpern, in Reference Module in Neuroscience and Biobehavioral Psychology, 2017. Olfactory receptors were first identified from rats by Linda Buck and Richard Axel in 1991 . After a comprehensive study was published (44) in which the widespread expression of OR transcripts in many human tissues was demonstrated, an intensive discussion began regarding the functional roles of ectopically expressed ORs. Examples of the pronounced expression of non-deorphanized receptors are OR6B3 in the retina and TG, as well as OR4N4 in spermatozoa (48, 49, 83). Free MCFAs that activate OR51E1 have been identified in human plasma and epicardial adipose tissue (32, 82). www.sciencedaily.com/releases/2017/02/170208094029.htm (accessed November 22, 2021). Recovery is possible if the receptor end is damaged, but loss of an entire trigeminal neuron is permanent. The influx of calcium begins a cascade of events within … Vertebrates Ors are G-protein-coupled receptors, stimulated by odors to produce intracellular second messengers that gate ion channels. 10.1152/physrev.00013.2017.—Olfactory receptors (ORs) are not exclusively ex-pressed in the olfactory sensory neurons; they are also observed outside of the olfactory system in all other human tissues tested to date, including the testis, lung, intestine, skin, heart, and blood. Individual ORNs are not permanent structures. If a fatty acid activates the receptor, it triggers a negative effect: the heart rate and the force of muscular contraction are reduced. Senses 36 781–790. A major obstacle in discovering the physiological function is the limited knowledge regarding their activating agonists. The neuroanatomical overlap between neurons that mediate olfaction and emotions provides an anatomical basis for the capacity of odors to produce hedonic responses. Additionally, there are limited data regarding Gq activation in enterochromaffin and colorectal cancer cells (17, 191).
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