title: Theophylline induces changes in the electro-olfactogram  of the mouse.
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 microg/mg. Theophylline seems to be taken up into the olfactory epithelium of supravital mice and to interact with the olfactory signal transduction.
authors.affiliation: Department of Otorhinolaryngology, University of Dresden Medical School, Fetscherstr. 74,01307 Dresden, Germany.Volker.Gudziol@uniklinikum-dresden.de
authors.forename: Volker
authors.initials: V
authors.lastname: Gudziol
authors.forename: Jorg
authors.initials: J
authors.lastname: Pietsch
authors.forename: Martin
authors.initials: M
authors.lastname: Witt
authors.forename: Thomas
authors.initials: T
authors.lastname: Hummel
mesh_terms: D000281:Administration, Intranasal; D000818:Animals; D002851:Chromatography, High Pressure Liquid; D004195:Disease Models, Animal; D004585:Electrooculography / Q000187:drug effects*; D005260:Female; D051379:Mice; D000857:Olfaction Disorders / Q000188:drug therapy* / Q000378:metabolism / Q000503:physiopathology; D009831:Olfactory Mucosa / Q000187:drug effects / Q000378:metabolism / Q000503:physiopathology; D010726:Phosphodiesterase Inhibitors / Q000008:administration & dosage* / Q000493:pharmacokinetics; D015398:Signal Transduction / Q000187:drug effects / Q000502:physiology; D012903:Smell / Q000187:drug effects*; D013806:Theophylline / Q000008:administration & dosage* / Q000493:pharmacokinetics; D016896:Treatment Outcome
chemical_list: D010726:Phosphodiesterase Inhibitors; D013806:Theophylline