Abstract
The vertebrate olfactory system recognizes and discriminates between thousands of structurally diverse odorants. Detection of odorants in mammals is mediated by olfactory receptors (ORs), which comprise the largest superfamily of G protein-coupled receptors (GPCRs). Upon odorant binding, ORs couple to G proteins, resulting in an increase in intracellular cAMP levels and subsequent receptor signaling. In this review, we will discuss recently published studies outlining the molecular basis of odor discrimination, focusing on pharmacology, G protein activation, and desensitization of ORs. A greater understanding of the molecular mechanisms underlying OR activity may help in the discovery of agonists and antagonists of ORs, and of GPCRs with potential therapeutic applications.
Similar content being viewed by others
Abbreviations
- AC:
-
Adenylyl cyclase
- β1AR:
-
β1-Adrenergic receptor
- β2AR:
-
β2-Adrenergic receptor
- CaM:
-
Calmodulin
- CaMKII:
-
Calcium/CaM-dependent protein kinase II
- CNG channel:
-
Cyclic nucleotide-gated channel
- GC:
-
Guanylyl cyclase
- GG:
-
Grueneberg ganglion
- GPCR:
-
G protein-coupled receptor
- GRK:
-
GPCR kinase
- Helix8:
-
Eighth intracellular helical domain
- IC3:
-
Third intracellular loop
- MOE:
-
Main olfactory epithelium
- OB:
-
Olfactory bulb
- OR:
-
Olfactory receptor
- OSN:
-
Olfactory sensory neuron
- PCR:
-
Polymerase chain reaction
- PKA:
-
Protein kinase A
- PKC:
-
Protein kinase C
- PLC/IP3 :
-
Phospholipase C/inositol-1,4,5-triphosphate
- SO:
-
Septal organ
- TAAR:
-
Trace amine-associated receptor
- TM:
-
Transmembrane
References
Spehr M, Munger SD (2009) Olfactory receptors: G protein-coupled receptors and beyond. J Neurochem 109:1570–1583
Touhara K, Vosshall LB (2009) Sensing odorants and pheromones with chemosensory receptors. Annu Rev Physiol 71:307–332
Buck L, Axel R (1991) A novel multigene family may encode odorant receptors: a molecular basis for odor recognition. Cell 65:175–187
Man O, Gilad Y, Lancet D (2004) Prediction of the odorant binding site of olfactory receptor proteins by human-mouse comparisons. Protein Sci 13:240–254
Malnic B, Godfrey PA, Buck LB (2004) The human olfactory receptor gene family. Proc Natl Acad Sci USA 101:2584–2589
Niimura Y, Nei M (2007) Extensive gains and losses of olfactory receptor genes in mammalian evolution. PLoS ONE 2, e708
Zhang X, De la Cruz O, Pinto JM, Nicolae D, Firestein S, Gilad Y (2007) Characterizing the expression of the human olfactory receptor gene family using a novel DNA microarray. Genome Biol 8:R86
Godfrey PA, Malnic B, Buck LB (2004) The mouse olfactory receptor gene family. Proc Natl Acad Sci USA 101:2156–2161
Zhang X, Firestein S (2002) The olfactory receptor gene superfamily of the mouse. Nat Neurosci 5:124–133
Zhang X, Rodriguez I, Mombaerts P, Firestein S (2004) Odorant and vomeronasal receptor genes in two mouse genome assemblies. Genomics 83:802–811
Alioto TS, Ngai J (2005) The odorant receptor repertoire of teleost fish. BMC Genomics 6:173
Niimura Y, Nei M (2005) Evolutionary dynamics of olfactory receptor genes in fishes and tetrapods. Proc Natl Acad Sci USA 102:6039–6044
Bargmann CI (1998) Neurobiology of the Caenorhabditis elegans genome. Science 282:2028–2033
Robertson HM, Warr CG, Carlson JR (2003) Molecular evolution of the insect chemoreceptor gene superfamily in Drosophila melanogaster. Proc Natl Acad Sci USA 100(Suppl 2):14537–14542
Clyne PJ, Warr CG, Freeman MR, Lessing D, Kim J, Carlson JR (1999) A novel family of divergent seven-transmembrane proteins: candidate odorant receptors in Drosophila. Neuron 22:327–338
Gao Q, Chess A (1999) Identification of candidate Drosophila olfactory receptors from genomic DNA sequence. Genomics 60:31–39
Vosshall LB, Amrein H, Morozov PS, Rzhetsky A, Axel R (1999) A spatial map of olfactory receptor expression in the Drosophila antenna. Cell 96:725–736
Hill CA, Fox AN, Pitts RJ, Kent LB, Tan PL, Chrystal MA, Cravchik A, Collins FH, Robertson HM, Zwiebel LJ (2002) G protein-coupled receptors in Anopheles gambiae. Science 298:176–178
Abdel-Latief M (2007) A family of chemoreceptors in Tribolium castaneum (Tenebrionidae: Coleoptera). PLoS ONE 2:e1319
Engsontia P, Sanderson AP, Cobb M, Walden KK, Robertson HM, Brown S (2008) The red flour beetle’s large nose: an expanded odorant receptor gene family in Tribolium castaneum. Insect Biochem Mol Biol 38:387–397
Robertson HM, Wanner KW (2006) The chemoreceptor superfamily in the honey bee, Apis mellifera: expansion of the odorant, but not gustatory, receptor family. Genome Res 16:1395–1403
Warren WC, Hillier LW, Marshall Graves JA, Birney E, Ponting CP, Grutzner F, Belov K, Miller W, Clarke L, Chinwalla AT, Yang SP, Heger A, Locke DP, Miethke P, Waters PD, Veyrunes F, Fulton L, Fulton B, Graves T, Wallis J, Puente XS, Lopez-Otin C, Ordonez GR, Eichler EE, Chen L, Cheng Z, Deakin JE, Alsop A, Thompson K, Kirby P, Papenfuss AT, Wakefield MJ, Olender T, Lancet D, Huttley GA, Smit AF, Pask A, Temple-Smith P, Batzer MA, Walker JA, Konkel MK, Harris RS, Whittington CM, Wong ES, Gemmell NJ, Buschiazzo E, Vargas Jentzsch IM, Merkel A, Schmitz J, Zemann A, Churakov G, Kriegs JO, Brosius J, Murchison EP, Sachidanandam R, Smith C, Hannon GJ, Tsend-Ayush E, McMillan D, Attenborough R, Rens W, Ferguson-Smith M, Lefevre CM, Sharp JA, Nicholas KR, Ray DA, Kube M, Reinhardt R, Pringle TH, Taylor J, Jones RC, Nixon B, Dacheux JL, Niwa H, Sekita Y, Huang X, Stark A, Kheradpour P, Kellis M, Flicek P, Chen Y, Webber C, Hardison R, Nelson J, Hallsworth-Pepin K, Delehaunty K, Markovic C, Minx P, Feng Y, Kremitzki C, Mitreva M, Glasscock J, Wylie T, Wohldmann P, Thiru P, Nhan MN, Pohl CS, Smith SM, Hou S, Nefedov M, de Jong PJ, Renfree MB, Mardis ER, Wilson RK (2008) Genome analysis of the platypus reveals unique signatures of evolution. Nature 455:256
Nei M, Niimura Y, Nozawa M (2008) The evolution of animal chemosensory receptor gene repertoires: roles of chance and necessity. Nat Rev Genet 9:951–963
Benton R, Sachse S, Michnick SW, Vosshall LB (2006) Atypical membrane topology and heteromeric function of Drosophila odorant receptors in vivo. PLoS Biol 4:e20
Sato K, Pellegrino M, Nakagawa T, Vosshall LB, Touhara K (2008) Insect olfactory receptors are heteromeric ligand-gated ion channels. Nature 452:1002–1006
Wicher D, Schafer R, Bauernfeind R, Stensmyr MC, Heller R, Heinemann SH, Hansson BS (2008) Drosophila odorant receptors are both ligand-gated and cyclic-nucleotide-activated cation channels. Nature 452:1007–1011
Breer H, Fleischer J, Strotmann J (2006) The sense of smell: multiple olfactory subsystems. Cell Mol Life Sci 63:1465–1475
Munger SD, Leinders-Zufall T, Zufall F (2008) Subsystem organization of the mammalian sense of smell. Annu Rev Physiol 71:115–140
Zucchi R, Chiellini G, Scanlan TS, Grandy DK (2006) Trace amine-associated receptors and their ligands. Br J Pharmacol 149:967–978
Liberles SD, Buck LB (2006) A second class of chemosensory receptors in the olfactory epithelium. Nature 442:645–650
Hu J, Zhong C, Ding C, Chi Q, Walz A, Mombaerts P, Matsunami H, Luo M (2007) Detection of near-atmospheric concentrations of CO2 by an olfactory subsystem in the mouse. Science 317:953–957
Sun L, Wang H, Hu J, Han J, Matsunami H, Luo M (2009) Guanylyl cyclase-D in the olfactory CO2 neurons is activated by bicarbonate. Proc Natl Acad Sci USA 106:2041–2046
Leinders-Zufall T, Cockerham RE, Michalakis S, Biel M, Garbers DL, Reed RR, Zufall F, Munger SD (2007) Contribution of the receptor guanylyl cyclase GC-D to chemosensory function in the olfactory epithelium. Proc Natl Acad Sci USA 104:14507–14512
Lin W, Arellano J, Slotnick B, Restrepo D (2004) Odors detected by mice deficient in cyclic nucleotide-gated channel subunit A2 stimulate the main olfactory system. J Neurosci 24:3703–3710
Kaluza JF, Gussing F, Bohm S, Breer H, Strotmann J (2004) Olfactory receptors in the mouse septal organ. J Neurosci Res 76:442–452
Tian H, Ma M (2004) Molecular organization of the olfactory septal organ. J Neurosci 24:8383–8390
Fuss SH, Omura M, Mombaerts P (2005) The Grueneberg ganglion of the mouse projects axons to glomeruli in the olfactory bulb. Eur J Neurosci 22:2649–2654
Koos DS, Fraser SE (2005) The Grueneberg ganglion projects to the olfactory bulb. NeuroReport 16:1929–1932
Fleischer J, Schwarzenbacher K, Besser S, Hass N, Breer H (2006) Olfactory receptors and signalling elements in the Grueneberg ganglion. J Neurochem 98:543–554
Fleischer J, Schwarzenbacher K, Breer H (2007) Expression of trace amine-associated receptors in the Grueneberg ganglion. Chem Senses 32:623–631
Mamasuew K, Breer H, Fleischer J (2008) Grueneberg ganglion neurons respond to cool ambient temperatures. Eur J Neurosci 28:1775–1785
Brechbuhl J, Klaey M, Broillet MC (2008) Grueneberg ganglion cells mediate alarm pheromone detection in mice. Science 321:1092–1095
Zhao H, Ivic L, Otaki JM, Hashimoto M, Mikoshiba K, Firestein S (1998) Functional expression of a mammalian odorant receptor. Science 279:237–242
Serizawa S, Miyamichi K, Sakano H (2004) One neuron-one receptor rule in the mouse olfactory system. Trends Genet 20:648–653
Touhara K, Sengoku S, Inaki K, Tsuboi A, Hirono J, Sato T, Sakano H, Haga T (1999) Functional identification and reconstitution of an odorant receptor in single olfactory neurons. Proc Natl Acad Sci USA 96:4040–4045
Touhara K (2007) Deorphanizing vertebrate olfactory receptors: recent advances in odorant-response assays. Neurochem Int 51:132–139
Oka Y, Katada S, Omura M, Suwa M, Yoshihara Y, Touhara K (2006) Odorant receptor map in the mouse olfactory bulb: in vivo sensitivity and specificity of receptor-defined glomeruli. Neuron 52:857–869
Shirokova E, Schmiedeberg K, Bedner P, Niessen H, Willecke K, Raguse JD, Meyerhof W, Krautwurst D (2005) Identification of specific ligands for orphan olfactory receptors. G protein-dependent agonism and antagonism of odorants. J Biol Chem 280:11807–11815
Araneda RC, Kini AD, Firestein S (2000) The molecular receptive range of an odorant receptor. Nat Neurosci 3:1248–1255
Kajiya K, Inaki K, Tanaka M, Haga T, Kataoka H, Touhara K (2001) Molecular bases of odor discrimination: reconstitution of olfactory receptors that recognize overlapping sets of odorants. J Neurosci 21:6018–6025
Wetzel CH, Oles M, Wellerdieck C, Kuczkowiak M, Gisselmann G, Hatt H (1999) Specificity and sensitivity of a human olfactory receptor functionally expressed in human embryonic kidney 293 cells and Xenopus laevis oocytes. J Neurosci 19:7426–7433
Bozza T, Feinstein P, Zheng C, Mombaerts P (2002) Odorant receptor expression defines functional units in the mouse olfactory system. J Neurosci 22:3033–3043
Gaillard I, Rouquier S, Pin JP, Mollard P, Richard S, Barnabe C, Demaille J, Giorgi D (2002) A single olfactory receptor specifically binds a set of odorant molecules. Eur J Neurosci 15:409–418
Krautwurst D, Yau KW, Reed RR (1998) Identification of ligands for olfactory receptors by functional expression of a receptor library. Cell 95:917–926
Peterlin Z, Li Y, Sun G, Shah R, Firestein S, Ryan K (2008) The importance of odorant conformation to the binding and activation of a representative olfactory receptor. Chem Biol 15:1317–1327
Repicky SE, Luetje CW (2009) Molecular receptive range variation among mouse odorant receptors for aliphatic carboxylic acids. J Neurochem 109:193–202
Katada S, Hirokawa T, Oka Y, Suwa M, Touhara K (2005) Structural basis for a broad but selective ligand spectrum of a mouse olfactory receptor: mapping the odorant-binding site. J Neurosci 25:1806–1815
Abaffy T, Matsunami H, Luetje CW (2006) Functional analysis of a mammalian odorant receptor subfamily. J Neurochem 97:1506–1518
Spehr M, Gisselmann G, Poplawski A, Riffell JA, Wetzel CH, Zimmer RK, Hatt H (2003) Identification of a testicular odorant receptor mediating human sperm chemotaxis. Science 299:2054–2058
Saito H, Chi Q, Zhuang H, Matsunami H, Mainland JD (2009) Odor coding by a Mammalian receptor repertoire. Sci Signal 2, ra9
Keller A, Zhuang H, Chi Q, Vosshall LB, Matsunami H (2007) Genetic variation in a human odorant receptor alters odour perception. Nature 449:468–472
Yoshikawa K, Touhara K (2009) Myr-Ric-8A enhances G(alpha15)-mediated Ca2+ response of vertebrate olfactory receptors. Chem Senses 34:15–23
Abaffy T, Malhotra A, Luetje CW (2007) The molecular basis for ligand specificity in a mouse olfactory receptor: a network of functionally important residues. J Biol Chem 282:1216–1224
Oka Y, Nakamura A, Watanabe H, Touhara K (2004) An odorant derivative as an antagonist for an olfactory receptor. Chem Senses 29:815–822
Oka Y, Omura M, Kataoka H, Touhara K (2004) Olfactory receptor antagonism between odorants. EMBO J 23:120–126
Katada S, Hirokawa T, Touhara K (2008) Exploring the odorant binding site of a G-protein-coupled olfactory receptor. Curr Comput Aided Drug Des 4:123–131
Mombaerts P (2004) Genes and ligands for odorant, vomeronasal and taste receptors. Nat Rev Neurosci 5:263–278
Wong ST, Trinh K, Hacker B, Chan GC, Lowe G, Gaggar A, Xia Z, Gold GH, Storm DR (2000) Disruption of the type III adenylyl cyclase gene leads to peripheral and behavioral anosmia in transgenic mice. Neuron 27:487–497
Zheng J, Zagotta WN (2004) Stoichiometry and assembly of olfactory cyclic nucleotide-gated channels. Neuron 42:411–421
Stephan AB, Shum EY, Hirsh S, Cygnar KD, Reisert J, Zhao H (2009) ANO2 is the cilial calcium-activated chloride channel that may mediate olfactory amplification. Proc Natl Acad Sci USA 106:11776–11781
Schroeder BC, Cheng T, Jan YN, Jan LY (2008) Expression cloning of TMEM16A as a calcium-activated chloride channel subunit. Cell 134:1019–1029
Yang YD, Cho H, Koo JY, Tak MH, Cho Y, Shim WS, Park SP, Lee J, Lee B, Kim BM, Raouf R, Shin YK, Oh U (2008) TMEM16A confers receptor-activated calcium-dependent chloride conductance. Nature 455:1210–1215
Belluscio L, Gold GH, Nemes A, Axel R (1998) Mice deficient in G(olf) are anosmic. Neuron 20:69–81
Brunet LJ, Gold GH, Ngai J (1996) General anosmia caused by a targeted disruption of the mouse olfactory cyclic nucleotide-gated cation channel. Neuron 17:681–693
Lin W, Margolskee R, Donnert G, Hell SW, Restrepo D (2007) Olfactory neurons expressing transient receptor potential channel M5 (TRPM5) are involved in sensing semiochemicals. Proc Natl Acad Sci USA 104:2471–2476
Fulle HJ, Vassar R, Foster DC, Yang RB, Axel R, Garbers DL (1995) A receptor guanylyl cyclase expressed specifically in olfactory sensory neurons. Proc Natl Acad Sci USA 92:3571–3575
Elsaesser R, Montani G, Tirindelli R, Paysan J (2005) Phosphatidyl-inositide signalling proteins in a novel class of sensory cells in the mammalian olfactory epithelium. Eur J Neurosci 21:2692–2700
Kato A, Katada S, Touhara K (2008) Amino acids involved in conformational dynamics and G protein coupling of an odorant receptor: targeting gain-of-function mutation. J Neurochem 107:1261–1270
Eason MG, Liggett SB (1995) Identification of a Gs coupling domain in the amino terminus of the third intracellular loop of the alpha 2A-adrenergic receptor. Evidence for distinct structural determinants that confer Gs versus Gi coupling. J Biol Chem 270:24753–24760
Franke RR, Sakmar TP, Graham RM, Khorana HG (1992) Structure and function in rhodopsin. Studies of the interaction between the rhodopsin cytoplasmic domain and transducin. J Biol Chem 267:14767–14774
Liggett SB, Caron MG, Lefkowitz RJ, Hnatowich M (1991) Coupling of a mutated form of the human beta 2-adrenergic receptor to Gi and Gs. Requirement for multiple cytoplasmic domains in the coupling process. J Biol Chem 266:4816–4821
Thiagaraj HV, Ortiz TC, Devereaux MC Jr, Seaver B, Hall B, Parker KK (2007) Regulation of G proteins by human 5-HT1a receptor TM3/i2 and TM5/i3 loop peptides. Neurochem Int 50:109–118
Liggett SB (2002) Update on current concepts of the molecular basis of beta2-adrenergic receptor signaling. J Allergy Clin Immunol 110:S223–S227
Marin EP, Krishna AG, Zvyaga TA, Isele J, Siebert F, Sakmar TP (2000) The amino terminus of the fourth cytoplasmic loop of rhodopsin modulates rhodopsin–transducin interaction. J Biol Chem 275:1930–1936
Nikiforovich GV, Taylor CM, Marshall GR (2007) Modeling of the complex between transducin and photoactivated rhodopsin, a prototypical G-protein-coupled receptor. Biochemistry 46:4734–4744
Delos Santos NM, Gardner LA, White SW, Bahouth SW (2006) Characterization of the residues in helix 8 of the human beta1-adrenergic receptor that are involved in coupling the receptor to G proteins. J Biol Chem 281:12896–12907
Acharya S, Saad Y, Karnik SS (1997) Transducin-alpha C-terminal peptide binding site consists of C–D and E–F loops of rhodopsin. J Biol Chem 272:6519–6524
Farrens DL, Altenbach C, Yang K, Hubbell WL, Khorana HG (1996) Requirement of rigid-body motion of transmembrane helices for light activation of rhodopsin. Science 274:768–770
Sheikh SP, Zvyaga TA, Lichtarge O, Sakmar TP, Bourne HR (1996) Rhodopsin activation blocked by metal-ion-binding sites linking transmembrane helices C and F. Nature 383:347–350
Ballesteros JA, Jensen AD, Liapakis G, Rasmussen SG, Shi L, Gether U, Javitch JA (2001) Activation of the beta 2-adrenergic receptor involves disruption of an ionic lock between the cytoplasmic ends of transmembrane segments 3 and 6. J Biol Chem 276:29171–29177
Palczewski K, Kumasaka T, Hori T, Behnke CA, Motoshima H, Fox BA, Le Trong I, Teller DC, Okada T, Stenkamp RE, Yamamoto M, Miyano M (2000) Crystal structure of rhodopsin: A G protein-coupled receptor. Science 289:739–745
Zufall F, Leinders-Zufall T (2000) The cellular and molecular basis of odor adaptation. Chem Senses 25:473–481
Bradley J, Bonigk W, Yau KW, Frings S (2004) Calmodulin permanently associates with rat olfactory CNG channels under native conditions. Nat Neurosci 7:705–710
Bradley J, Reuter D, Frings S (2001) Facilitation of calmodulin-mediated odor adaptation by cAMP-gated channel subunits. Science 294:2176–2178
Munger SD, Lane AP, Zhong H, Leinders-Zufall T, Yau KW, Zufall F, Reed RR (2001) Central role of the CNGA4 channel subunit in Ca2+-calmodulin-dependent odor adaptation. Science 294:2172–2175
Song Y, Cygnar KD, Sagdullaev B, Valley M, Hirsh S, Stephan A, Reisert J, Zhao H (2008) Olfactory CNG channel desensitization by Ca2+/CaM via the B1b subunit affects response termination but not sensitivity to recurring stimulation. Neuron 58:374–386
Wei J, Zhao AZ, Chan GC, Baker LP, Impey S, Beavo JA, Storm DR (1998) Phosphorylation and inhibition of olfactory adenylyl cyclase by CaM kinase II in Neurons: a mechanism for attenuation of olfactory signals. Neuron 21:495–504
Yan C, Zhao AZ, Bentley JK, Loughney K, Ferguson K, Beavo JA (1995) Molecular cloning and characterization of a calmodulin-dependent phosphodiesterase enriched in olfactory sensory neurons. Proc Natl Acad Sci USA 92:9677–9681
Ferguson SS (2001) Evolving concepts in G protein-coupled receptor endocytosis: the role in receptor desensitization and signaling. Pharmacol Rev 53:1–24
Pitcher JA, Freedman NJ, Lefkowitz RJ (1998) G protein-coupled receptor kinases. Annu Rev Biochem 67:653–692
Willets JM, Challiss RA, Nahorski SR (2003) Non-visual GRKs: are we seeing the whole picture? Trends Pharmacol Sci 24:626–633
Benovic JL, Kuhn H, Weyand I, Codina J, Caron MG, Lefkowitz RJ (1987) Functional desensitization of the isolated beta-adrenergic receptor by the beta-adrenergic receptor kinase: potential role of an analog of the retinal protein arrestin (48-kDa protein). Proc Natl Acad Sci USA 84:8879–8882
Lohse MJ, Benovic JL, Codina J, Caron MG, Lefkowitz RJ (1990) beta-Arrestin: a protein that regulates beta-adrenergic receptor function. Science 248:1547–1550
Hausdorff WP, Bouvier M, O’Dowd BF, Irons GP, Caron MG, Lefkowitz RJ (1989) Phosphorylation sites on two domains of the beta 2-adrenergic receptor are involved in distinct pathways of receptor desensitization. J Biol Chem 264:12657–12665
Dawson TM, Arriza JL, Jaworsky DE, Borisy FF, Attramadal H, Lefkowitz RJ, Ronnett GV (1993) Beta-adrenergic receptor kinase-2 and beta-arrestin-2 as mediators of odorant-induced desensitization. Science 259:825–829
Boekhoff I, Inglese J, Schleicher S, Koch WJ, Lefkowitz RJ, Breer H (1994) Olfactory desensitization requires membrane targeting of receptor kinase mediated by beta gamma-subunits of heterotrimeric G proteins. J Biol Chem 269:37–40
Peppel K, Boekhoff I, McDonald P, Breer H, Caron MG, Lefkowitz RJ (1997) G protein-coupled receptor kinase 3 (GRK3) gene disruption leads to loss of odorant receptor desensitization. J Biol Chem 272:25425–25428
Mashukova A, Spehr M, Hatt H, Neuhaus EM (2006) Beta-arrestin2-mediated internalization of mammalian odorant receptors. J Neurosci 26:9902–9912
Neuhaus EM, Mashukova A, Barbour J, Wolters D, Hatt H (2006) Novel function of beta-arrestin2 in the nucleus of mature spermatozoa. J Cell Sci 119:3047–3056
Levai O, Feistel T, Breer H, Strotmann J (2006) Cells in the vomeronasal organ express odorant receptors but project to the accessory olfactory bulb. J Comp Neurol 498:476–490
Dulac C, Axel R (1995) A novel family of genes encoding putative pheromone receptors in mammals. Cell 83:195–206
Herrada G, Dulac C (1997) A novel family of putative pheromone receptors in mammals with a topographically organized and sexually dimorphic distribution. Cell 90:763–773
Matsunami H, Buck LB (1997) A multigene family encoding a diverse array of putative pheromone receptors in mammals. Cell 90:775–784
Ryba NJ, Tirindelli R (1997) A new multigene family of putative pheromone receptors. Neuron 19:371–379
Juilfs DM, Fulle HJ, Zhao AZ, Houslay MD, Garbers DL, Beavo JA (1997) A subset of olfactory neurons that selectively express cGMP-stimulated phosphodiesterase (PDE2) and guanylyl cyclase-D define a unique olfactory signal transduction pathway. Proc Natl Acad Sci USA 94:3388–3395
Meyer MR, Angele A, Kremmer E, Kaupp UB, Muller F (2000) A cGMP-signaling pathway in a subset of olfactory sensory neurons. Proc Natl Acad Sci USA 97:10595–10600
Reisert J, Lai J, Yau KW, Bradley J (2005) Mechanism of the excitatory Cl-response in mouse olfactory receptor neurons. Neuron 45:553–561
Author information
Authors and Affiliations
Corresponding author
Rights and permissions
About this article
Cite this article
Kato, A., Touhara, K. Mammalian olfactory receptors: pharmacology, G protein coupling and desensitization. Cell. Mol. Life Sci. 66, 3743–3753 (2009). https://doi.org/10.1007/s00018-009-0111-6
Received:
Revised:
Accepted:
Published:
Issue Date:
DOI: https://doi.org/10.1007/s00018-009-0111-6