title: 2,4,6-trichloroanisole is a potent suppressor of olfactory signal transduction.
abstract: We investigated the sensitivity of single olfactory receptor cells to 2,4,6-trichloroanisole (TCA), a compound known for causing cork taint in wines. Such off-flavors have been thought to originate from unpleasant odor qualities evoked by contaminants. However, we here show that TCA attenuates olfactory transduction by suppressing cyclic nucleotide-gated channels, without evoking odorant responses. Surprisingly, suppression was observed even at extremely low (i.e., attomolar) TCA concentrations. The high sensitivity to TCA was associated with temporal integration of the suppression effect. We confirmed that potent suppression by TCA and similar compounds was correlated with their lipophilicity, as quantified by the partition coefficient at octanol/water boundary (pH 7.4), suggesting that channel suppression is mediated by a partitioning of TCA into the lipid bilayer of plasma membranes. The rank order of suppression matched human recognition of off-flavors: TCA equivalent to 2,4,6-tribromoanisole, which is much greater than 2,4,6-trichlorophenol. Furthermore, TCA was detected in a wide variety of foods and beverages surveyed for odor losses. Our findings demonstrate a potential molecular mechanism for the reduction of flavor.
authors.affiliation: Department of Biophysical Dynamics, Graduate School of Frontier Biosciences, Osaka University, Osaka 560-8531, Japan.
authors.forename: Hiroko
authors.initials: H
authors.lastname: Takeuchi
authors.forename: Hiroyuki
authors.initials: H
authors.lastname: Kato
authors.forename: Takashi
authors.initials: T
authors.lastname: Kurahashi
mesh_terms: D000818:Animals; D000840:Anisoles / Q000494:pharmacology*; D054815:Cyclic Nucleotide-Gated Cation Channels / Q000037:antagonists & inhibitors*; D004305:Dose-Response Relationship, Drug; D008401:Gas Chromatography-Mass Spectrometry; D000442:Octanols; D009812:Odorants / Q000032:analysis*; D018034:Olfactory Receptor Neurons / Q000378:metabolism; D018408:Patch-Clamp Techniques; D012455:Salamandridae; D015398:Signal Transduction / Q000187:drug effects* / Q000502:physiology; D012903:Smell / Q000502:physiology*; D013268:Stimulation, Chemical; D014920:Wine / Q000032:analysis
chemical_list: D000840:Anisoles; D054815:Cyclic Nucleotide-Gated Cation Channels; D000442:Octanols; C110228:2,4,6-trichloroanisole
keywords: ion channel; olfactory masking; patch-clamp
references.citation: Nature. 1997 Feb 20;385(6618):725-9
references.pmid: 9034189
references.citation: J Neurosci. 2005 Apr 6;25(14):3586-92
references.pmid: 15814789
references.citation: J Physiol. 1989 Dec;419:177-92
references.pmid: 2621628
references.citation: J Biosci Bioeng. 2005 Aug;100(2):178-83
references.pmid: 16198261
references.citation: J Neurosci. 2008 Jan 16;28(3):766-75
references.pmid: 18199776
references.citation: Proc Natl Acad Sci U S A. 2009 Jul 14;106(28):11776-81
references.pmid: 19561302
references.citation: J Physiol. 2010 Nov 1;588(Pt 21):4189-204
references.pmid: 20837642
references.citation: Proc Natl Acad Sci U S A. 1995 Aug 15;92(17):7864-8
references.pmid: 7544007
references.citation: J Physiol. 2002 Jun 15;541(Pt 3):825-33
references.pmid: 12068043
references.citation: J Theor Biol. 1978 Mar 7;71(1):39-48
references.pmid: 642521
references.citation: J Gen Physiol. 2003 Nov;122(5):557-67
references.pmid: 14581582
references.citation: Science. 2005 Jun 24;308(5730):1931-4
references.pmid: 15976304
references.citation: J Biol Chem. 2011 Aug 12;286(32):28041-8
references.pmid: 21646359
references.citation: Cell. 1991 Apr 5;65(1):175-87
references.pmid: 1840504
references.citation: Proc Natl Acad Sci U S A. 1987 Jan;84(2):585-9
references.pmid: 2432613
references.citation: Nature. 1972 Jan 28;235(5335):222-3
references.pmid: 4551127
references.citation: BMC Neurosci. 2013 Apr 08;14:45
references.pmid: 23565900
references.citation: Biophys J. 1997 Mar;72(3):1193-203
references.pmid: 9138566
references.citation: Neuroreport. 1991 Jan;2(1):5-8
references.pmid: 1722719
references.citation: J Gen Physiol. 2006 Sep;128(3):365-71
references.pmid: 16940558
references.citation: Nature. 1995 Feb 2;373(6513):435-7
references.pmid: 7830795
references.citation: J Neurosci. 1991 Nov;11(11):3624-9
references.pmid: 1941099
references.citation: J Gen Physiol. 2003 Sep;122(3):349-63
references.pmid: 12939394
references.citation: Science. 1994 Jul 1;265(5168):118-20
references.pmid: 8016645
references.citation: J Gen Physiol. 2009 Jun;133(6):583-601
references.pmid: 19433623
references.citation: J Hazard Mater. 2009 Aug 30;168(1):246-52
references.pmid: 19272699
references.citation: Brain Res. 1985 Dec 16;359(1-2):97-103
references.pmid: 4075164
references.citation: Science. 1966 Oct 14;154(3746):270-1
references.pmid: 5914760
references.citation: J Neurosci. 2005 Nov 30;25(48):11084-91
references.pmid: 16319308
references.citation: Pflugers Arch. 1981 Aug;391(2):85-100
references.pmid: 6270629
references.citation: Nature. 1993 May 6;363(6424):71-4
references.pmid: 7683113
references.citation: Nature. 1993 Nov 18;366(6452):283-6
references.pmid: 8232590
references.citation: J Physiol. 1993 Jul;466:287-302
references.pmid: 8410695
references.citation: Nihon Seirigaku Zasshi. 1995;57(3):127-33
references.pmid: 7666378
references.citation: J Physiol Sci. 2011 May;61(3):231-45
references.pmid: 21431980
references.citation: Chem Senses. 2010 Sep;35(7):533-9
references.pmid: 20519266