title: Human trace amine-associated receptor TAAR5 can be activated by trimethylamine.
abstract: In addition to the canonical olfactory receptors, TAARs were currently suggested to be a second class of chemosensory receptors in the olfactory epithelium of vertebrates. In contrast to several deorphanized murine TAARs, agonists for the intact human TAAR genes 2, 5, 6, 8 and 9 that are potentially expressed in the human olfactory epithelium have not been determined so far. Moreover, the physiological relevance of TAARs still remains elusive. We present the first successful functional expression of a human TAAR and agonists of human TAAR5. We performed a ligand screening using recombinantly expressed human TAAR5 in HANA3A cells and Xenopus laevis oocytes. In order to measure receptor activity, we used a cAMP-dependent reporter gene assay and two-electrode voltage clamp technique. As a result, human TAAR5 can be activated in a concentration-dependent manner by trimethylamine and with less efficacy by dimethylethylamine. It could neither be activated by any other of the tested single amines with a related chemical structure (42 in total), nor by any of the tested odorant mixtures. The hypothesis that Single Nucleotide Polymorphisms (SNP) within the reading frame of an olfactory receptor gene can cause a specific anosmia, formed the basis for clarifying the question, if anosmia for trimethylamine is caused by a SNP in a TAAR coding sequence. All functional human TAAR gene reading frames of subjects with specific anosmia for trimethylamine were amplified and products analyzed regarding SNP distribution. We demonstrated that the observed specific anosmia for trimethylamine is not correlated with a SNP in the coding sequence of one of the putatively functional human TAAR genes.
authors: Department of Cell Physiology, Ruhr-University Bochum, Bochum, Germany. Ivonne.Wallrabenstein@rub.de
authors: Ivonne
authors: I
authors: Wallrabenstein
authors: Jonas
authors: J
authors: Kuklan
authors: Lea
authors: L
authors: Weber
authors: Sandra
authors: S
authors: Zborala
authors: Markus
authors: M
authors: Werner
authors: Janine
authors: J
authors: Altmüller
authors: Christian
authors: C
authors: Becker
authors: Anna
authors: A
authors: Schmidt
authors: Hanns
authors: H
authors: Hatt
authors: Thomas
authors: T
authors: Hummel
authors: Günter
authors: G
authors: Gisselmann
mesh_terms: D002460:Cell Line; D005021:Ethylamines / Q000494:pharmacology; D006801:Humans; D008744:Methylamines / Q000494:pharmacology*; D009831:Olfactory Mucosa / Q000187:drug effects / Q000378:metabolism; D018034:Olfactory Receptor Neurons / Q000378:metabolism; D016366:Open Reading Frames / Q000235:genetics; D043562:Receptors, G-Protein-Coupled / Q000187:drug effects* / Q000378:metabolism*
chemical_list: D005021:Ethylamines; D008744:Methylamines; D043562:Receptors, G-Protein-Coupled; C047305:N,N-dimethylethylamine; C023336:trimethylamine
references: Drug Metab Dispos. 2001 Apr;29(4 Pt 2):517-21
references: 11259343
references: J Neurochem. 2006 Jun;97(5):1506-18
references: 16606354
references: Nat Protoc. 2008;3(9):1402-13
references: 18772867
references: J Neurosci. 1999 Sep 1;19(17):7426-33
references: 10460249
references: Nature. 2007 Sep 27;449(7161):468-72
references: 17873857
references: Proc Natl Acad Sci U S A. 2012 Aug 14;109(33):13410-5
references: 22837392
references: J Biol Chem. 2007 May 18;282(20):15284-93
references: 17387175
references: Science. 1982 Feb 26;215(4536):1127-9
references: 7063846
references: J Biol Chem. 2008 Apr 18;283(16):10470-5
references: 18281286
references: Hum Mutat. 2013 Jan;34(1):32-41
references: 22936402
references: Proc Natl Acad Sci U S A. 2001 Jul 31;98(16):8966-71
references: 11459929
references: Cell. 2004 Nov 24;119(5):679-91
references: 15550249
references: J Proteome Res. 2006 Feb;5(2):378-84
references: 16457604
references: Bioinformatics. 2009 Aug 15;25(16):2078-9
references: 19505943
references: PLoS One. 2010 Jun 15;5(6):e11133
references: 20559446
references: Br J Pharmacol. 2006 Dec;149(8):967-78
references: 17088868
references: Genome Biol. 2009;10(3):R25
references: 19261174
references: Mol Pharmacol. 2001 Dec;60(6):1181-8
references: 11723224
references: Proc Natl Acad Sci U S A. 2011 Jul 5;108(27):11235-40
references: 21690383
references: BMC Med Genet. 2007 Jan 27;8:2
references: 17257434
references: ACS Chem Biol. 2012 Jul 20;7(7):1184-9
references: 22545963
references: Cell Rep. 2012 Jul 26;2(1):76-88
references: 22840399
references: Ann N Y Acad Sci. 2009 Jul;1170:168-72
references: 19686131
references: Sci Signal. 2009 Mar 03;2(60):ra9
references: 19261596
references: PLoS Biol. 2007 Oct 30;5(11):e284
references: 17973576
references: Biol Psychol. 2003 Jul;63(3):269-79
references: 12853171
references: J Exp Zool. 1989 Sep;251(3):300-5
references: 2769207
references: Nature. 2006 Aug 10;442(7103):645-50
references: 16878137
references: Proc Natl Acad Sci U S A. 2006 Jun 13;103(24):9310-4
references: 16754875
references: PLoS One. 2011 Mar 30;6(3):e18353
references: 21479135
references: Pharmacol Biochem Behav. 1985 Mar;22(3):497-500
references: 4039452
references: J Biochem. 2011 Sep;150(3):257-66
references: 21771869
references: Curr Biol. 2013 Jan 7;23(1):11-20
references: 23177478