Skip to main content
Log in

Theophylline induces changes in the electro-olfactogram of the mouse

  • Rhinology
  • Published:
European Archives of Oto-Rhino-Laryngology Aims and scope Submit manuscript

Abstract

Options for the treatment of hyposmia are limited; available therapies do not provide a long-lasting effect. A recent study suggests that an unspecific phosphodiesterase inhibitor (PDE-I) increases olfactory sensitivity due to interaction with the signal transduction in the olfactory epithelium. The aim of the present study was to investigate whether theophylline, an unspecific PDE-I, evokes changes in the electro-olfactogram (EOG) which would support the hypothesis of a drug-related impact on signal transduction. In addition, the uptake of topically administered theophylline in the olfactory epithelium should be investigated. EOG was obtained in 29 samples of supravital mouse olfactory epithelia. Olfactory stimulation (phenylethyl alcohol, PEA and hydrogen sulfide, H2S) was performed using an air-dilution olfactometer. Theophylline concentration in the olfactory epithelium of five samples was measured by means of high pressure liquid chromatography. Administration of theophylline resulted in a tendency towards smaller EOG amplitudes (p = 0.055), being reduced by 13 and 25% in response to stimulation with PEA or H2S, respectively. In comparison to the application of Ringer’s solution, theophylline resulted in a significant (p = 0.031) decrease of the EOG amplitude. Latency was not significantly (p = 0.10) influenced by drug administration. The theophylline concentration in the olfactory epithelium ranged from 0.21 to 1.53 μg/mg. Theophylline seems to be taken up into the olfactory epithelium of supravital mice and to interact with the olfactory signal transduction.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Fig. 1

Similar content being viewed by others

References

  1. Vennemann MM, Hummel T, Berger K (2008) The association between smoking and smell and taste impairment in the general population. J Neurol 255(8):1121–1126

    Article  PubMed  Google Scholar 

  2. Santos DV, Reiter ER, DiNardo LJ, Costanzo RM (2004) Hazardous events associated with impaired olfactory function. Arch Otolaryngol Head Neck Surg 130(3):317–319

    Article  PubMed  Google Scholar 

  3. Temmel AF, Quint C, Schickinger-Fischer B, Klimek L, Stoller E, Hummel T (2002) Characteristics of olfactory disorders in relation to major causes of olfactory loss. Arch Otolaryngol Head Neck Surg 128:635–641

    PubMed  Google Scholar 

  4. Miwa T, Furukawa M, Tsukatani T, Costanzo RM, DiNardo LJ, Reiter ER (2001) Impact of olfactory impairment on quality of life and disability. Arch Otorhinolaryngol Head Neck Surg 127:497–503

    CAS  Google Scholar 

  5. Blomqvist EH, Lundblad L, Bergstedt H, Stjarne P (2003) Placebo-controlled, randomized, double-blind study evaluating the efficacy of fluticasone propionate nasal spray for the treatment of patients with hyposmia/anosmia. Acta Otolaryngol 123(7):862–868

    Article  CAS  PubMed  Google Scholar 

  6. Gudziol V, Hummel T (2009) Effects of pentoxifylline on olfactory sensitivity: a postmarketing surveillance study. Arch Otolaryngol Head Neck Surg 135(3):291–295

    Article  PubMed  Google Scholar 

  7. Nakamura T (2000) Cellular and molecular constituents of olfactory sensation in vertebrates. Comp Biochem Physiol 126(1):17–32

    CAS  Google Scholar 

  8. Ottoson D (1956) Analysis of the electrical activity of the olfactory epithelium. Acta Physiol Scand 35:1–83

    Google Scholar 

  9. Knecht M, Hummel T (2004) Recording of the human electro-olfactogram. Physiol Behav 83(1):13–19

    CAS  PubMed  Google Scholar 

  10. Scott JW, Davis LM, Shannon D, Kaplan C (1996) Relation of chemical structure to spatial distribution of sensory responses in rat olfactory epithelium. J Neurophysiol 75(5):2036–2049

    CAS  PubMed  Google Scholar 

  11. Mackay-Sim A, Kesteven S (1994) Topographic patterns of responsiveness to odorants in the rat olfactory epithelium. J Neurophysiol 71:150–160

    CAS  PubMed  Google Scholar 

  12. Scott JW, Brierley T, Schmidt FH (2000) Chemical determinants of the rat electro-olfactogram. J Neurosci 20(12):4721–4731

    CAS  PubMed  Google Scholar 

  13. Gesteland RC, Lettvin JY, Pitts WH (1965) Chemical transmission in the nose of the frog. J Physiol 181(3):525–559

    CAS  PubMed  Google Scholar 

  14. Henkin RI, Velicu I, Schmidt L (2009) An open-label controlled trial of theophylline for treatment of patients with hyposmia. Am J Med Sci 337(6):396–406

    Article  PubMed  Google Scholar 

  15. Levy LM, Henkin RI, Lin CS, Hutter A, Schellinger D (1998) Increased brain activation in response to odors in patients with hyposmia after theophylline treatment demonstrated by fMRI. J Comput Assist Tomogr 22:760–770

    Article  CAS  PubMed  Google Scholar 

  16. Mozell MM (1962) Olfactory mucosal and neural responses in the frog. Am J Physiol 203:353–358

    CAS  PubMed  Google Scholar 

  17. Mackay-Sim A, Kubie J (1981) The salamander nose: a model system for the study of spatial coding of olfactory quality. Chem Senses 6:249–257

    Article  Google Scholar 

  18. Wong ST, Trinh K, Hacker B, Chan GC, Lowe G, Gaggar A et al (2000) Disruption of the type III adenylyl cyclase gene leads to peripheral and behavioral anosmia in transgenic mice. Neuron 27(3):487–497

    Article  CAS  PubMed  Google Scholar 

  19. Michalakis S, Reisert J, Geiger H, Wetzel C, Zong X, Bradley J et al (2006) Loss of CNGB1 protein leads to olfactory dysfunction and subciliary cyclic nucleotide-gated channel trapping. J Biol Chem 281(46):35156–35166

    Article  CAS  PubMed  Google Scholar 

  20. Cygnar KD, Zhao H (2009) Phosphodiesterase 1C is dispensable for rapid response termination of olfactory sensory neurons. Nat Neurosci 12(4):454–462

    Article  CAS  PubMed  Google Scholar 

Download references

Conflict of interest statement

The authors declare that they have no conflict of interest.

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to Volker Gudziol.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Gudziol, V., Pietsch, J., Witt, M. et al. Theophylline induces changes in the electro-olfactogram of the mouse. Eur Arch Otorhinolaryngol 267, 239–243 (2010). https://doi.org/10.1007/s00405-009-1076-7

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s00405-009-1076-7

Keywords

Navigation