576
Views
32
CrossRef citations to date
0
Altmetric
Review Article

Nasal odorant metabolism: enzymes, activity and function in olfaction

, &
Pages 224-245 | Received 10 Apr 2019, Accepted 10 Jun 2019, Published online: 09 Jul 2019

References

  • Aceto A, Di Ilio C, Angelucci S, Longo V, Gervasi PG, Federici G. 1989. Glutathione transferases in human nasal mucosa. Arch Toxicol. 63:427–431.
  • Al-Ghabeish M, Scheetz T, Assem M, Donovan MD. 2015. Microarray Determination of the Expression of Drug Transporters in Humans and Animal Species Used for the Investigation of Nasal Absorption. Mol Pharm. 12(8):2742–2754.
  • Andersen M, Sarangapani R, Gentry R, Clewell H, Covington T, Frederick CB. 2000. Application of a hybrid CFD-PBPK nasal dosimetry model in an inhalation risk assessment: an example with acrylic acid. Toxicol Sci. 57:312–325.
  • Andersen ME, Green T, Frederick CB, Bogdanffy MS. 2002. Physiologically based pharmacokinetic (PBPK) models for nasal tissue dosimetry of organic esters: assessing the state-of-knowledge and risk assessment applications with methyl methacrylate and vinyl acetate. Regul Toxicol Pharmacol. 36:234–245.
  • Asakawa M, Fukutani Y, Savangsuksa A, Noguchi K, Matsunami H, Yohda M. 2017. Modification of the response of olfactory receptors to acetophenone by CYP1a2. Sci Rep. 7:10167.
  • Banger KK, Foster JR, Lock EA, Reed CJ. 1994. Immunohistochemical localisation of six glutathione S-transferases within the nasal cavity of the rat. Arch Toxicol. 69:91–98.
  • Ben-Arie N, Khen M, Lancet D. 1993. Glutathione S-transferases in rat olfactory epithelium: purification, molecular properties and odorant biotransformation. Biochem J. 292:379–384.
  • Bogdanffy MS. 1990. Biotransformation enzymes in the rodent nasal mucosa: the value of a histochemical approach. Environ Health Perspect. 85:177–186.
  • Bogdanffy MS, Kee CR, Hinchman CA, Trela BA. 1991. Metabolism of dibasic esters by rat nasal mucosal carboxylesterase. Drug Metab Dispos. 19:124–129.
  • Bogdanffy MS, Randall HW, Morgan KT. 1986. Histochemical localization of aldehyde dehydrogenase in the respiratory tract of the Fischer-344 rat. Toxicol Appl Pharmacol. 82:560–567.
  • Bogdanffy MS, Sarangapani R, Kimbell JS, Frame SR, Plowchalk DR. 1998. Analysis of vinyl acetate metabolism in rat and human nasal tissues by an in vitro gas uptake technique. Toxicol Sci. 46:235–246.
  • Bogdanffy MS, Taylor ML. 1993. Kinetics of nasal carboxylesterase-mediated metabolism of vinyl acetate. Drug Metab Dispos. 21:1107–1111.
  • Bond JA, Martin OS, Birnbaum LS, Dahl AR, Melnick RL, Henderson RF. 1988. Metabolism of 1,3-butadiene by lung and liver microsomes of rats and mice repeatedly exposed by inhalation to 1,3-butadiene. Toxicol Lett. 44:143–151.
  • Borst P, Elferink RO. 2002. Mammalian ABC transporters in health and disease. Annu Rev Biochem. 71:537–592.
  • Brittebo E, Brandt I. 1984. Metabolism of chlorobenzene in the mucosa of the murine respiratory tract. Lung. 162:79–88.
  • Brittebo E, Löfberg B, Tjälve H. 1981. Extrahepatic sites of metabolism of N-nitrosopyrrolidine in mice and rats. Xenobiotica. 11:619–625.
  • Brittebo EB. 1982. N-Demethylation of aminopyrine by the nasal mucosa in mice and rats. Acta Pharmacol Toxicol. 51:227–232.
  • Brittebo EB. 1987. Metabolic activation of phenacetin in rat nasal mucosa: dose-dependent binding to the glands of Bowman. Cancer Res. 47:1449–1456.
  • Brittebo EB. 1997. Metabolism-dependent activation and toxicity of chemicals in nasal glands. Mutat Res. 380:61–75.
  • Bush ML, Frederick CB, Kimbell JS, Ultman JS. 1998. A CFD-PBPK hybrid model for simulating gas and vapor uptake in the rat nose. Toxicol Appl Pharmacol. 150:133–145.
  • Campbell JL, Andersen ME, Clewell HJ. 2014. A hybrid CFD-PBPK model for naphthalene in rat and human with IVIVE for nasal tissue metabolism and cross-species dosimetry. Inhal Toxicol. 26:333–344.
  • Carr WE, Gleeson RA, Trapido-Rosenthal HG. 1990. The role of perireceptor events in chemosensory processes. Trends Neurosci. 13:212–215.
  • Chougnet A, Woggon WD, Locher E, Schilling B. 2009. Synthesis and in vitro activity of heterocyclic inhibitors of CYP2A6 and CYP2A13, two cytochrome P450 enzymes present in the respiratory tract. Chembiochem. 10:1562–1567.
  • Coureaud G, Langlois D, Sicard G, Schaal B. 2004. Newborn rabbit responsiveness to the mammary pheromone is concentration-dependent. Chem Senses. 29:341–350.
  • Crowe TP, Greenlee MHW, Kanthasamy AG, Hsu WH. 2018. Mechanism of intranasal drug delivery directly to the brain. Life Sci. 195:44–52.
  • Dahl AR. 1982. The inhibition of rat nasal cytochrome P-450-dependent mono-oxygenase by the essence heliotropin (piperonal). Drug Metab Dispos. 10:553–554.
  • Dahl AR. 1986. Activation of nitrosamines to mutagens by rat and rabbit nasal, lung and liver S-9 homogenates. Adv Exp Med Biol. 197:367–372.
  • Dahl AR, Bond JA, Petridou-Fischer J, Sabourin PJ, Whaley SJ. 1988. Effects of the respiratory tract on inhaled materials. Toxicol Appl Pharmacol. 93:484–492.
  • Dahl AR, Brezinski DA. 1985. Inhibition of rabbit nasal and hepatic cytochrome P-450-dependent hexamethylphosphoramide (HMPA) N-demethylase by methylenedioxyphenyl compounds. Biochem Pharmacol. 34:631–636.
  • Dahl AR, Coslett DS, Bond JA, Hesseltine GR. 1985. Metabolism of benzo[a]pyrene on the nasal mucosa of Syrian hamsters: comparison to metabolism by other extrahepatic tissues and possible role of nasally produced metabolites in carcinogenesis. J Natl Cancer Inst. 75:135–139.
  • Dahl AR, Hadley WM. 1983. Formaldehyde production promoted by rat nasal cytochrome P-450-dependent monooxygenases with nasal decongestants, essences, solvents, air pollutants, nicotine, and cocaine as substrates. Toxicol Appl Pharmacol. 67:200–205.
  • Dahl AR, Hadley WM. 1991. Nasal cavity enzymes involved in xenobiotic metabolism: effects on the toxicity of inhalants. Crit Rev Toxicol. 21:345–372.
  • Dahl AR, Hadley WM, Hahn FF, Benson JM, McClellan RO. 1982. Cytochrome P-450-dependent monooxygenases in olfactory epithelium of dogs: possible role in tumorigenicity. Science. 216:57–59.
  • Dahl AR, Miller SC, Petridou-Fischer J. 1987. Carboxylesterases in the respiratory tracts of rabbits, rats and Syrian hamsters. Toxicol Lett. 36:129–136.
  • Debat H, Eloit C, Blon F, Sarazin B, Henry C, Huet JC, Trotier D, Pernollet JC. 2007. Identification of human olfactory cleft mucus proteins using proteomic analysis. J Proteome Res. 6:1985–1996.
  • Dhuria SV, Hanson LR, Frey WH. 2010. Intranasal delivery to the central nervous system: mechanisms and experimental considerations. J Pharm Sci. 99:1654–1673.
  • Ding X, Peng HM, Coon MJ. 1992. Cytochromes P450 NMa, NMb (2G1), and LM4 (1A2) are differentially expressed during development in rabbit olfactory mucosa and liver. Mol Pharmacol. 42:1027–1032.
  • Ding XX, Coon MJ. 1991. Purification and characterization of cytochromes P450 in rabbit nasal microsomes. Meth Enzymol. 206:603–612.
  • Ding XX, Porter TD, Peng HM, Coon MJ. 1991. cDNA and derived amino acid sequence of rabbit nasal cytochrome P450NMb (P450IIG1), a unique isozyme possibly involved in olfaction. Arch Biochem Biophys. 285:120–125.
  • Doring B, Petzinger E. 2014. Phase 0 and phase III transport in various organs: combined concept of phases in xenobiotic transport and metabolism. Drug Metab Rev. 46(3):261–282.
  • Durand N, Carot-Sans G, Bozzolan F, Rosell G, Siaussat D, Debernard S, Chertemps T, Maibeche-Coisne M. 2011. Degradation of pheromone and plant volatile components by a same odorant-degrading enzyme in the cotton leafworm, Spodoptera littoralis. PLoS One. 6:e29147.
  • Eisenbrandt DL, Nitschke KD. 1989. Inhalation toxicity of sulfuryl fluoride in rats and rabbits. Fundam Appl Toxicol. 12:540–557.
  • Faure P, Legendre A, Hanser HI, Andriot I, Artur Y, Guichard E, Coureaud G, Heydel JM. 2016. Odorant metabolism analysis by an automated ex vivo headspace gas-chromatography method. Chem Senses. 41:15–23.
  • Frederick CB, Bush ML, Lomax LG, Black KA, Finch L, Kimbell JS, Morgan KT, Subramaniam RP, Morris JB, Ultman JS. 1998. Application of a hybrid computational fluid dynamics and physiologically based inhalation model for interspecies dosimetry extrapolation of acidic vapors in the upper airways. Toxicol Appl Pharmacol. 152:211–231.
  • Frederick CB, Lomax LG, Black KA, Finch L, Scribner HE, Kimbell JS, Morgan KT, Subramaniam RP, Morris JB. 2002. Use of a hybrid computational fluid dynamics and physiologically based inhalation model for interspecies dosimetry comparisons of ester vapors. Toxicol Appl Pharmacol. 183:23–40.
  • Getchell TV, Margolis FL, Getchell ML. 1984. Perireceptor and receptor events in vertebrate olfaction. Prog Neurobiol. 23:317–345.
  • Gloede E, Cichocki JA, Baldino JB, Morris JB. 2011. A validated hybrid computational fluid dynamics-physiologically based pharmacokinetic model for respiratory tract vapor absorption in the human and rat and its application to inhalation dosimetry of diacetyl. Toxicol Sci. 123:231–246.
  • Hada N, Netzer WJ, Belhassan F, Wennogle LP, Gizurarson S. 2017. Nose-to-brain transport of imatinib mesylate: A pharmacokinetic evaluation. Eur J Pharm Sci. 102:46–54.
  • Hadley K, Orlandi RR, Fong KJ. 2004. Basic anatomy and physiology of olfaction and taste. Otolaryngol Clin North Am. 37:1115–1126.
  • Hadley WM, Dahl AR. 1982. Cytochrome P-450 dependent monooxygenase activity in rat nasal epithelial membranes. Toxicol Lett. 10:417–422.
  • Hadley WM, Dahl AR. 1983. Cytochrome P-450-dependent monooxygenase activity in nasal membranes of six species. Drug Metab Dispos. 11:275–276.
  • Hadley WM, Dahl AR, Benson JM, Hahn FF, McClellan RO. 1982. Cytochrome P450 dependent monooxygenases in nasal epithelial membranes: effect of phenobarbital and benzo(A)pyrene. Proc West Pharmacol Soc. 25:197–199.
  • Hanser HI, Faure P, Robert-Hazotte A, Artur Y, Duchamp-Viret P, Coureaud G, Heydel JM. 2017. Odorant-odorant metabolic interaction, a novel actor in olfactory perception and behavioral responsiveness. Sci Rep. 7:10219.
  • Harkema JR, Carey SA, Wagner JG. 2006. The nose revisited: a brief review of the comparative structure, function, and toxicologic pathology of the nasal epithelium. Toxicol Pathol. 34:252–269.
  • He P, Zhang YN, Li ZQ, Yang K, Zhu JY, Liu SJ, Dong SL. 2014. An antennae-enriched carboxylesterase from Spodoptera exigua displays degradation activity in both plant volatiles and female sex pheromones. Insect Mol Biol. 23:475–486.
  • Heydel JM, Coelho A, Thiebaud N, Legendre A, Le Bon AM, Faure P, Neiers F, Artur Y, Golebiowski J, Briand L. 2013. Odorant-binding proteins and xenobiotic metabolizing enzymes: implications in olfactory perireceptor events. Anat Rec. 296:1333–1345.
  • Heydel JM, Hanser HI, Faure P, Neiers F. 2016. Odorant metabolizing enzymes in the peripheral olfactory process flavour: from food to perception. London (UK): Wiley Blackwell; p. 1333–1345.
  • Heydel JM, Holsztynska EJ, Legendre A, Thiebaud N, Artur Y. 2010. UDP-Glucuronosyltransferases (UGTs) in neuro-olfactory tissues: expression, regulation, and function. Drug Metab Rev. 42:71–94.
  • Hu J, Sheng L, Li L, Zhou X, Xie F, D'Agostino J, Li Y, Ding X. 2014. Essential role of the cytochrome P450 enzyme CYP2A5 in olfactory mucosal toxicity of naphthalene. Drug Metab Dispos. 42:23–27.
  • Ishida Y, Leal WS. 2005. Rapid inactivation of a moth pheromone. Proc Natl Acad Sci U S A. 102:14075–14079.
  • Ishida Y, Leal WS. 2008. Chiral discrimination of the Japanese beetle sex pheromone and a behavioral antagonist by a pheromone-degrading enzyme. PNAS. 105:9076–9080.
  • Jedlitschky G, Cassidy AJ, Sales M, Pratt N, Burchell B. 1999. Cloning and characterization of a novel human olfactory UDP-glucuronosyltransferase. Biochem J. 340(Pt 3):837–843.
  • Jeffrey AM, Iatropoulos MJ, Williams GM. 2006. Nasal cytotoxic and carcinogenic activities of systemically distributed organic chemicals. Toxicol Pathol. 34:827–852.
  • Kaler G, Truong DM, Khandelwal A, Nagle M, Eraly SA, Swaan PW, Nigam SK. 2007. Structural variation governs substrate specificity for organic anion transporter (OAT) homologs. Potential remote sensing by OAT family members. J Biol Chem. 282:23841–23853.
  • Kaler G, Truong DM, Sweeney DE, Logan DW, Nagle M, Wu W, Eraly SA, Nigam SK. 2006. Olfactory mucosa-expressed organic anion transporter, Oat6, manifests high affinity interactions with odorant organic anions. Biochem Biophys Res Commun. 351:872–876.
  • Kamisaka K, Listowsky I, Gatmaitan Z, Arias IM. 1975. Interactions of bilirubin and other ligands with ligandin. Biochemistry. 14:2175–2180.
  • Kang N, Koo J. 2012. Olfactory receptors in non-chemosensory tissues. BMB Rep. 45:612–622.
  • Kida H, Fukutani Y, Mainland JD, de March CA, Vihani A, Li YR, Chi Q, Toyama A, Liu L, Kameda M, et al. 2018. Vapor detection and discrimination with a panel of odorant receptors. Nat Commun. 9:4556.
  • Kirsch F, Beauchamp J, Buettner A. 2012. Time-dependent aroma changes in breast milk after oral intake of a pharmacological preparation containing 1,8-cineole. Clin Nutr. 31:682–692.
  • Kirsch F, Buettner A. 2013. Characterisation of the metabolites of 1,8-cineole transferred into human milk: concentrations and ratio of enantiomers. Metabolites. 3:47–71.
  • Krishna NS, Getchell TV, Dhooper N, Awasthi YC, Getchell ML. 1995. Age- and gender-related trends in the expression of glutathione S-transferases in human nasal mucosa. Ann Otol Rhinol Laryngol. 104:812–822.
  • Krishna NS, Getchell TV, Getchell ML. 1994. Differential expression of alpha, mu, and pi classes of glutathione S-transferases in chemosensory mucosae of rats during development. Cell Tissue Res. 275:435–450.
  • Kuhlmann K, Tschapek A, Wiese H, Eisenacher M, Meyer HE, Hatt HH, Oeljeklaus S, Warscheid B. 2014. The membrane proteome of sensory cilia to the depth of olfactory receptors. Mol Cell Proteomics. 13:1828–1843.
  • Kuntova B, Stopkova R, Stopka P. 2018. Transcriptomic and proteomic profiling revealed high proportions of odorant binding and antimicrobial defense proteins in olfactory tissues of the house mouse. Front Genet. 9:26.
  • Lazard D, Zupko K, Poria Y, Net P, Lazarovits J, Horn S, Khen M, Lancet D. 1991. Odorant signal termination by olfactory UDP glucuronosyl transferase. Nature. 349:790–793.
  • Leclerc S, Heydel J-M, Amossé V, Gradinaru D, Cattarelli M, Artur Y, Goudonnet H, Magdalou J, Netter P, Pelczar H, et al. 2002. Glucuronidation of odorant molecules in the rat olfactory system: activity, expression and age-linked modifications of UDP-glucuronosyltransferase isoforms, UGT1A6 and UGT2A1, and relation to mitral cell activity. Brain Res Mol Brain Res. 107:201–213.
  • Legendre A, Faure P, Tiesset H, Potin C, Jakob I, Sicard G, Schaal B, Artur Y, Coureaud G, Heydel JM. 2014. When the nose must remain responsive: glutathione conjugation of the mammary pheromone in the newborn rabbit. Chem Senses. 39:425–437.
  • Malnic B, Hirono J, Sato T, Buck LB. 1999. Combinatorial receptor codes for odors. Cell. 96:713–723.
  • Mannervik B, Board PG, Hayes JD, Listowsky I, Pearson WR. 2005. Nomenclature for mammalian soluble glutathione transferases. Meth Enzymol. 401:1–8.
  • Mayer U, Ungerer N, Klimmeck D, Warnken U, Schnolzer M, Frings S, Mohrlen F. 2008. Proteomic analysis of a membrane preparation from rat olfactory sensory cilia. Chem Senses. 33:145–162.
  • Minn A, Leclerc S, Heydel J-M, Minn A-L, Denizot C, Cattarelli M, Netter P, Gradinaru D. 2002. Drug transport into the mammalian brain: the nasal pathway and its specific metabolic barrier. J Drug Target. 10:285–296.
  • Minn AL, Pelczar H, Denizot C, Martinet M, Heydel JM, Walther B, Minn A, Goudonnet H, Artur Y. 2005. Characterization of microsomal cytochrome P450-dependent monooxygenases in the rat olfactory mucosa. Drug Metab Dispos: Biol Fate Chem. 33:1229–1237.
  • Molinas A, Sicard G, Jakob I. 2012. Functional evidence of multidrug resistance transporters (MDR) in rodent olfactory epithelium. PLoS One. 7(5):e36167.
  • Morris JB, Hassett DN, Blanchard KT. 1993. A physiologically based pharmacokinetic model for nasal uptake and metabolism of nonreactive vapors. Toxicol Appl Pharmacol. 123:120–129.
  • Nagashima A, Touhara K. 2010. Enzymatic conversion of odorants in nasal mucus affects olfactory glomerular activation patterns and odor perception. J Neurosci. 30:16391–16398.
  • Nakagawa J, Ishikura S, Asami J, Isaji T, Usami N, Hara A, Sakurai T, Tsuritani K, Oda K, Takahashi M, et al. 2002. Molecular characterization of mammalian dicarbonyl/L-xylulose reductase and its localization in kidney. J Biol Chem. 277:17883–17891.
  • Nebert DW. 1994. Drug-metabolizing enzymes in ligand-modulated transcription. Biochem Pharmacol. 47:25–37.
  • Nef P, Heldman J, Lazard D, Margalit T, Jaye M, Hanukoglu I, Lancet D. 1989. Olfactory-specific cytochrome P-450. cDNA cloning of a novel neuroepithelial enzyme possibly involved in chemoreception. J Biol Chem. 264:6780–6785.
  • Neuhaus EM, Mashukova A, Zhang W, Barbour J, Hatt H. 2006. A specific heat shock protein enhances the expression of mammalian olfactory receptor proteins. Chem Senses. 31:445–452.
  • Neuser F, Zorn H, Berger RG. 2000. Generation of odorous acyloins by yeast pyruvate decarboxylases and their occurrence in sherry and soy sauce. J Agric Food Chem. 48(12):6191–6195.
  • Nigam SK, Bush KT, Martovetsky G, Ahn SY, Liu HC, Richard E, Bhatnagar V, Wu W. 2015. The organic anion transporter (OAT) family: a systems biology perspective. Physiol Rev. 95(1):83–123.
  • Niimura Y, Matsui A, Touhara K. 2014. Extreme expansion of the olfactory receptor gene repertoire in African elephants and evolutionary dynamics of orthologous gene groups in 13 placental mammals. Genome Res. 24:1485–1496.
  • Oliveira P, Fortuna A, Alves G, Falcao A. 2016. Drug-metabolizing enzymes and efflux transporters in nasal epithelium: influence on the bioavailability of intranasally administered drugs. Curr Drug Metab. 17:628–647.
  • Patel RM, Pinto JM. 2014. Olfaction: anatomy, physiology, and disease. Clin Anat. 27:54–60.
  • Pelosi P. 1996. Perireceptor events in olfaction. J Neurobiol. 30:3–19.
  • Pereira ME, Macri NP, Creasy DM. 2011. Evaluation of the rabbit nasal cavity in inhalation studies and a comparison with other common laboratory species and man. Toxicol Pathol. 39:893–900.
  • Reed CJ. 1993. Drug metabolism in the nasal cavity: relevance to toxicology. Drug Metab Rev. 25:173–205.
  • Robert-Hazotte A, Faure P, Neiers F, Potin C, Artur Y, Coureaud G, Heydel JM. 2019a. Nasal mucus glutathione transferase activity and impact on olfactory perception and neonatal behavior. Sci Rep. 9:3104.
  • Robert-Hazotte A, Schoumacker R, Semon E, Briand L, Guichard E, Le Quere JL, Faure P, Heydel JM. 2019b. Ex vivo real-time monitoring of volatile metabolites resulting from nasal odorant metabolism. Sci Rep. 9:2492.
  • Robert-Hazotte A, Thomas-Danguin T, Fèvre T, Potin C, Heydel JM, Faure P. 2018. Odorants' metabolism in human: a critical role in odor perception revealed. 43(7): E240-E240 in Senses Proceedings of The 40th Annual Meeting – Association for Chemoreception Sciences (AChemS), 16 and 17 April 2018, Florida (USA): Bonita Springs.
  • Rybczynski R, Reagan J, Lerner MR. 1989. A pheromone-degrading aldehyde oxidase in the antennae of the moth Manduca sexta. J Neurosci. 9:1341–1353.
  • Sabourin PJ, Tynes RE, Philpot RM, Winquist S, Dahl AR. 1988. Distribution of microsomal monooxygenases in the rabbit respiratory tract. Drug Metab Dispos. 16:557–562.
  • Sarangapani R, Teeguarden JG, Gentry PR, Clewell HJ 3rd, Barton HA, Bogdanffy MS. 2004. Interspecies dose extrapolation for inhaled dimethyl sulfate: a PBPK model-based analysis using nasal cavity N7-methylguanine adducts. Inhal Toxicol. 16:593–605.
  • Sarkar MA. 1992. Drug metabolism in the nasal mucosa. Pharm Res. 9:1–9.
  • Schaal B, Coureaud G, Langlois D, Ginies C, Semon E, Perrier G. 2003. Chemical and behavioural characterization of the rabbit mammary pheromone. Nature. 424:68–72.
  • Schilling B. 2017. Perireceptor processes in the nose - biochemical events beyond olfactory receptor activation. In: Handbook of Odors (Buettner A ed), Springer.
  • Schilling B, Kaiser R, Natsch A, Gautschi M. 2010. Investigation of odors in the fragrance industry [review]. Chemoecology. 20:135–147.
  • Schoumacker R, Robert-Hazotte A, Heydel JM, Faure P, Le Quere JL. 2016. Real-time monitoring of the metabolic capacity of ex vivo rat olfactory mucosa by proton transfer reaction mass spectrometry (PTR-MS). Anal Bioanal Chem. 408(6):1539–1543.
  • Scott JW, Scott-Johnson PE. 2002. The electroolfactogram: a review of its history and uses. Microsc Res Tech. 58:152–160.
  • Stott WT, Gollapudi BB, Rao KS. 2001. Mammalian toxicity of 1,3-dichloropropene. Rev Environ Contam Toxicol. 168:1–42.
  • Sweeney LM, Kirman CR, Gannon SA, Thrall KD, Gargas ML, Kinzell JH. 2009. Development of a physiologically based pharmacokinetic (PBPK) model for methyl iodide in rats, rabbits, and humans. Inhal Toxicol. 21:552–582.
  • Szyszka P, Gerkin RC, Galizia CG, Smith BH. 2014. High-speed odor transduction and pulse tracking by insect olfactory receptor neurons. Proc Natl Acad Sci U S A. 111:16925–16930.
  • Tamura H, Miyawaki A, Inoh N, Harada Y, Mikoshiba K, Matsui M. 1997. High sulfotransferase activity for phenolic aromatic odorants present in the mouse olfactory organ. Chem Biol Interact. 104:1–9.
  • Teeguarden JG, Bogdanffy MS, Covington TR, Tan C, Jarabek AM. 2008. A PBPK model for evaluating the impact of aldehyde dehydrogenase polymorphisms on comparative rat and human nasal tissue acetaldehyde dosimetry. Inhal Toxicol. 20:375–390.
  • Thiebaud N, Sigoillot M, Chevalier J, Artur Y, Heydel JM, Le Bon AM. 2010. Effects of typical inducers on olfactory xenobiotic-metabolizing enzyme, transporter, and transcription factor expression in rats. Drug Metab Dispos. 38:1865–1875.
  • Thiebaud N, Veloso Da Silva S, Jakob I, Sicard G, Chevalier J, Menetrier F, Berdeaux O, Artur Y, Heydel JM, Le Bon AM. 2013. Odorant metabolism catalyzed by olfactory mucosal enzymes influences peripheral olfactory responses in rats. PLoS One. 8:e59547.
  • Thomas-Danguin T, Sinding C, Romagny S, El Mountassir F, Atanasova B, Le Berre E, Le Bon AM, Coureaud G. 2014. The perception of odor objects in everyday life: a review on the processing of odor mixtures. Front Psychol. 5:504.
  • Thornton-Manning JR, Dahl AR. 1997. Metabolic capacity of nasal tissue interspecies comparisons of xenobiotic-metabolizing enzymes. Mutat Res. 380:43–59.
  • Vogt RG, Riddiford LM, Prestwich GD. 1985. Kinetic properties of a sex pheromone-degrading enzyme: the sensillar esterase of Antheraea polyphemus. Proc Natl Acad Sci U S A. 82:8827–8831.
  • Wallace BD, Redinbo MR. 2013. Xenobiotic-sensing nuclear receptors involved in drug metabolism: a structural perspective. Drug Metab Rev. 45:79–100.
  • Walliczek-Dworschak U, Hummel T. 2017. The human sense of olfaction. Facial Plast Surg. 33:396–404.
  • Wang Q, Titlow WB, McClintock DA, Stromberg AJ, McClintock TS. 2017. Activity-dependent gene expression in the mammalian olfactory epithelium. Chem Senses. 42:611–624.
  • Werner S, Nies E. 2018. Olfactory dysfunction revisited: a reappraisal of work-related olfactory dysfunction caused by chemicals. J Occup Med Toxicol. 13:28.
  • Werner S, Nies E. 2018. Olfactory dysfunction revisited: a reappraisal of work-related olfactory dysfunction caused by chemicals. J Occup Med Toxicol. 13:28.
  • Wu W, Bush KT, Liu HC, Zhu C, Abagyan R, Nigam SK. 2015. Shared Ligands Between Organic Anion Transporters (OAT1 and OAT6) and Odorant Receptors. Drug Metab Dispos. 43(12):1855–1863.
  • Wu W, Dnyanmote AV, Nigam SK. 2011. Remote communication through solute carriers and ATP binding cassette drug transporter pathways: an update on the remote sensing and signaling hypothesis. Mol Pharmacol. 79:795–805.
  • Yoshikawa K, Wang H, Jaen C, Haneoka M, Saito N, Nakamura J, Adappa ND, Cohen NA, Dalton P. 2018. The human olfactory cleft mucus proteome and its age-related changes. Sci Rep. 8:17170.
  • Youngentob SL, Mozell MM, Sheehe PR, Hornung DE. 1987. A quantitative analysis of sniffing strategies in rats performing odor detection tasks. Physiol Behav. 41:59–69.
  • Zaccone EJ, Goldsmith WT, Shimko MJ, Wells JR, Schwegler-Berry D, Willard PA, Case SL, Thompson JA, Fedan JS. 2015. Diacetyl and 2,3-pentanedione exposure of human cultured airway epithelial cells: ion transport effects and metabolism of butter flavoring agents. Toxicol Appl Pharmacol. 289:542–549.
  • Zhang X, Zhang QY, Liu D, Su T, Weng Y, Ling G, Chen Y, Gu J, Schilling B, Ding X. 2005. Expression of cytochrome p450 and other biotransformation genes in fetal and adult human nasal mucosa. Drug Metab Dispos. 33:1423–1428.
  • Zufall F, Nilius B, Flockerzi V. 2014. TRPs in Olfaction. Springer International Publishing. Mammalian Transient Receptor Potential (TRP) Cation Channels: Volume II:917–933.

Reprints and Corporate Permissions

Please note: Selecting permissions does not provide access to the full text of the article, please see our help page How do I view content?

To request a reprint or corporate permissions for this article, please click on the relevant link below:

Academic Permissions

Please note: Selecting permissions does not provide access to the full text of the article, please see our help page How do I view content?

Obtain permissions instantly via Rightslink by clicking on the button below:

If you are unable to obtain permissions via Rightslink, please complete and submit this Permissions form. For more information, please visit our Permissions help page.