Extrahepatic Microsomal Forms: Olfactory Cytochrome P450

  • X. Ding
  • M. J. Coon
Part of the Handbook of Experimental Pharmacology book series (HEP, volume 105)


The olfactory epithelium, which covers the nasal ethmoturbinates and the rear, upper portion of the nasal septum in mammals (cf. Rhodin 1974; Young 1986), has three major cell types: olfactory receptor cells (neurons), sustentacular cells (supporting cells), and the undifferentiated basal cells. Beneath the epithelium is a highly cellular lamina propria that is rich in blood vessels, connective tissue cells, nerve bundles, and Bowman’s glands. These glands are unique for the olfactory region, continuously secrete a serous fluid onto the olfactory surface, and, together with the supporting cells in the epithelium, constantly renew the surface fluid that overlays the olfactory mucosa (cf. Sorokin 1988; Getchell et al. 1988). Inevitably, the olfactory mucosa, which forms a barrier between the external environment in the nasal cavity and the subjacent brain tissues, is directly exposed to numerous inhaled foreign substances, such as odor ants, environmental pollutants, allergens, and pheromones, which readily reach the mucous layer and are absorbed into the subjacent cellular structures. Most of the absorbed compounds, particularly those that are lipophilic, undergo biotransformation to metabolites that are more hydrophilic before being excreted into the nasal cavity or cleared into the bloodstream.


Olfactory Epithelium Olfactory Mucosa Cytochrome P450 Isoforms Untreated Rabbit Undifferentiated Basal Cell 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.


Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.


  1. Adams DR, Jones AM, Plopper CG, Serabjit-Singh CJ, Philpot RM (1991) Distribution of cytochrome P-450 monooxygenase enzymes in the nasal mucosa of hamster and rat. Am J Anat 190: 291–298PubMedCrossRefGoogle Scholar
  2. Baron J, Voigt JM, Whitter TB, Kawabata TT, Knapp SA, Guengerich FP, Jakoby WB (1986) Identification of intratissue sites for xenobiotic activation and detoxication. Adv Exp Med Biol 197: 119–144PubMedGoogle Scholar
  3. Buchheit K, Walters E, Maruniak J (1991) Cytochrome P-450-like immunoreactivity in normal and naris closure mice. Abstracts of the 13th annual meeting of the Association for Chemoreception Sciences, Abstr No 45, April 17–21, Sarasota, FL, USAGoogle Scholar
  4. Dahl AR (1985) Activation of carcinogens and other xenobiotics by nasal cytochromes P-450. In: Boobis AR, Caldwell J, deMatteis F, Elcombe CR (eds) Microsomes and drug oxidations. Taylor and Francis, Philadelphia, p 299Google Scholar
  5. Dahl AR (1988) The effect of cytochrome P-450-dependent metabolism and other enzyme activities on olfaction. In: Margolis FL, Getchell TV (eds) Molecular neurobiology of the olfactory system. Plenum, New York, p 51CrossRefGoogle Scholar
  6. Dahl AR, Brezinski DA (1985) Inhibition of rabbit nasal and hepatic cytochrome P-450-dependent hexamethylphosphoramide ( HMPA) Af-demethylase by methylenedioxyphenyl compounds. Biochem Pharmacol 34: 631–636PubMedCrossRefGoogle Scholar
  7. Dahl AR, Hadley WM (1991) Nasal cavity enzymes involved in xenobiotic metabolism: effects on the toxicity of inhalants. Crit Rev Toxicol 21: 345–372PubMedCrossRefGoogle Scholar
  8. Ding X, Coon MJ (1988a) Cytochrome P-450-dependent formation of ethylene from TV-nitrosoethylamines. Drug Metab Dispos 16: 265–269PubMedGoogle Scholar
  9. Ding X, Coon MJ (1988b) Purification and characterization of two unique forms of cytochrome P-450 from rabbit nasal microsomes. Biochemistry 27: 8330–8337PubMedCrossRefGoogle Scholar
  10. Ding X, Coon MJ (1990a) Induction of cytochrome P-450 isozyme 3a (P-450IIE1) in rabbit olfactory mucosa by ethanol and acetone. Drug Metab Dispos 18: 742–745PubMedGoogle Scholar
  11. Ding X, Coon MJ (1990b) Immunochemical characterization of multiple forms of cytochrome P-450 in rabbit nasal microsomes and evidence for tissue-specific expression of P450s NMa and NMb. Mol Pharmacol 37: 489–496PubMedGoogle Scholar
  12. Ding X, Coon MJ (1991) Interaction of odorants and endogenous substrates with olfactory monooxygenases: possible role of cytochrome P-450 in the maintenance of steroid and fatty acid homeostasis in rabbit olfactory mucosa. FASEB J 5: A1519Google Scholar
  13. Ding X, Koop DR, Crump BL, Coon MJ (1986) Immunochemical identification of cytochrome P-450 isozyme 3a (P-450alc) in rabbit nasal and kidney microsomes and evidence for differential induction by alcohol. Mol Pharmacol 30: 370–378PubMedGoogle Scholar
  14. Ding X, Porter TD, Peng H-M, 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: 120–125Google Scholar
  15. Foster JR, Elcombe CR, Boobis AR, Davies DS, Sesardic D, McQuade J, Robson RT, Hayward C, Lock EA (1986) Immunochemical localization of cytochrome P-450 in hepatic and extrahepatic tissues of the rat with a monoclonal antibody against cytochrome P-450 c. Biochem Pharmacol 35: 4543–4554PubMedCrossRefGoogle Scholar
  16. Getchell ML, Zielinski B, Getchell TV (1988) Odorant and autonomic regulation of secretion in the olfactory mucosa. In: Margolis FL, Getchell TV (eds) Molecular neurobiology of the olfactory system. Plenum, New York, p 71CrossRefGoogle Scholar
  17. Gillner M, Brittebo EB, Brandt I, Söderkvist P, Appelgren L-E, Gustafsson J-A (1987) Uptake and specific binding of 2,3,7,8-tetrachlorodibenzo-p-dioxin in the olfactory mucosa of mice and rats. Cancer Res 47: 4150–4159PubMedGoogle Scholar
  18. Hong J-Y, Ding X, Smith T, Coon MJ, Yang CS (1991a) Metabolism of tobacco-specific carcinogen 4-(methylnitrosamino)-l-(3-pyridyl)-l-butanone (NNK) by rabbit nasal microsomes and P450s NMa and NMb. Proc Am Assoc Cancer Res 32: 120Google Scholar
  19. Hong J-Y, Smith T, Lee M-J, Li W, Ma B-L, Ning SM, Brady JF, Thomas PE, Yang CS (1991b) Metabolism of carcinogenic nitrosamines by rat nasal mucosa and the effect of diallyl sulfide. Cancer Res 51: 1509–1514PubMedGoogle Scholar
  20. Jayyosi Z, Thomas PE (1990) Identification of cytochrome P-450 isozymes and characterization of testosterone oxidation pathways in rat nasal epithelium. FASEB J 4: A1971Google Scholar
  21. Jenner J, Dodd GH (1988) Xenobiotic metabolism in the nasal epithelia. Drug Metabol Drug Interact 6: 123–148PubMedCrossRefGoogle Scholar
  22. Khani SC, Porter TP, Fujita VS, Coon MJ (1988) Organization and differential expression of two highly similar genes in the rabbit alcohol-inducible cytochrome P-450 subfamily. J Biol Chem 263: 7170–7175PubMedGoogle Scholar
  23. Kimura S, Kozak CA, Gonzalez FJ (1989) Identification of a novel P450 expressed in rat lung: cDNA cloning and sequence, chromosome mapping, and induction by 3-methylcholanthrene. Biochemistry 28: 3798–3803PubMedCrossRefGoogle Scholar
  24. Larsson P, Pettersson H, Tjlve H (1989) Metabolism of aflatoxin B1 in the bovine olfactory mucosa. Carcinogenesis 10: 1113–1118PubMedCrossRefGoogle Scholar
  25. Lazard D, Nathan T, Rubinstein M, Khen M, Lancet D, Zupko K (1990) Identification and biochemical analysis of novel olfactory-specific cytochrome P-450IIA and UDP-glucuronosyl transferase. Biochemistry 29: 7433–7440PubMedCrossRefGoogle Scholar
  26. Lazard D, Zupko K, Poria Y, Nef P, Lazarovits J, Horn S, Khen M, Lancet D (1991) Odorant signal termination by olfactory UDP glucuronosyl transferase. Nature 349: 790–793PubMedCrossRefGoogle Scholar
  27. Nebert DW, Nelson DR, Coon MJ, Estabrook RW, Feyereisen R, Fujii-Kuriyama Y, Gonzalez FJ, Guengerich FP, Gunsalus IC, Johnson EF, Loper JC, Sato R, Waterman MR, Waxman DJ (1991) The P450 superfamily: update on new sequences, gene mapping, and recommended nomenclature. DNA Cell Biol 10: 1–14PubMedCrossRefGoogle Scholar
  28. Nef P, Heldman J, Lazard D, Margalit T, Jaye M, Hanukoglu I, Lancet D (1989) Olfactory-specific cytochrome P-450. J Biol Chem 264: 6780–6785PubMedGoogle Scholar
  29. Nef P, Larabee TM, Kagimoto K, Meyer UA (1990a) Olfactory-specific cytochrome P-450 (P-450olfl; IIG1): gene structure and developmental regulation. J Biol Chem 265: 2903–2907PubMedGoogle Scholar
  30. Nef P, Kempf A, Fruh F, Meyer UA (1990b) Olfactory cytochrome P-450: molecular biology of P-450olfl (IIG) and P-450olf2 (IIIB), two novel olfactory specific cytochromes P-450 possibly involved in olfaction. In: Ingelman-Sundberg M, Gustafsson J-A, Orrenius S (eds) Proceedings of the 8th international symposium on microsomes and drug oxidations, Stockholm, Karolinska Institutet, Stockholm, p 10Google Scholar
  31. Porter TD, Khani SC, Coon MJ (1989) Induction and tissue-specific expression of rabbit cytochrome P450IIE1 and IIE2 genes. Mol Pharmacol 36: 61–65PubMedGoogle Scholar
  32. Reddy SL, Kim SG, States JC, Dahl AR, Hotchkiss J, Novak RF (1991) RT-PCR detection of CYP1A1, 1A2 and 2E1 mRNAs in rat nasal tissue. FASEB J 5: A1162Google Scholar
  33. Reed CJ, Lock EA, De Matteis F (1986) NADPH: cytochrome P-450 reductase in olfactory epithelium. Biochem J 240: 585–592PubMedGoogle Scholar
  34. Rhodin JAG (1974) Histology, a text and atlas. Oxford University Press, New York, p 608Google Scholar
  35. Roberts ES, Vaz ADN, Coon MJ (1991a) Metabolism of retinoids by rabbit P-450 cytochromes. FASEB J 5: A1514Google Scholar
  36. Roberts ES, Vaz ADN, Coon MJ (1991b) Catalysis by cytochrome P-450 of an oxidative reaction in xenobiotic aldehyde metabolism: deformylation with olefin formation. Proc Natl Acad Sci USA 88: 8963–8966PubMedCrossRefGoogle Scholar
  37. Sabourin PJ, Tynes RE, Philpot RM, Winquist S, Dahl AR (1988) Distribution of microsomal monooxygenases in the rabbit respiratory tract. Drug Metab Dispos 16: 557–562PubMedGoogle Scholar
  38. Schwab GE, Johnson EF (1987) Enzymology of rabbit cytochrome P-450. In: Guengerich FP (ed) Mammalian cytochromes P-450. CRC Press, Boca Raton, p 55Google Scholar
  39. Sorokin SP (1988) The respiratory system. In: Weiss L (ed) Cell and tissue biology, a textbook of histology. Urban and Schwarzenberg, Baltimore, p 752Google Scholar
  40. Voigt JM, Guengerich FP, Baron J (1985) Localization of a cytochrome P-450 isozyme (cytochrome P-450 PB-B) and NADPH-cytochrome P-450 reductase in rat nasal mucosa. Cancer Lett 27: 241–247PubMedCrossRefGoogle Scholar
  41. Williams DE, Ding X, Coon MJ (1990) Rabbit nasal cytochrome P-450 NMa has high activity as a nicotine oxidase. Biochem Biophys Res Commun 166: 945–952PubMedCrossRefGoogle Scholar
  42. Young JT (1986) Light microscopic examination of the rat nasal passages: preparation and morphologic features. In: Barrow CS (ed) Toxicology of the nasal passages. Hemisphere, Washington, p 27Google Scholar
  43. Zupko K, Poria Y, Lancet D (1991) Immunolocalization of cytochrome P-450olfl and P-450olf2 in rat olfactory mucosa. Eur J Biochem 196: 51–58PubMedCrossRefGoogle Scholar

Copyright information

© Springer-Verlag Berlin Heidelberg 1993

Authors and Affiliations

  • X. Ding
  • M. J. Coon

There are no affiliations available

Personalised recommendations