Human TAAR5 (hTAAR5) is a functional trace amine-associated receptor which acts as an olfactory receptor for tertiary amines.[8][9]Trimethylamine and N,N-dimethylethylamine are full agonists of hTAAR5.[9][10][11] The amber-woody fragrance timberol antagonizes this activity of trimethylamine.[12]3-Iodothyronamine is an inverse agonist of hTAAR5.[13][14] Recent studies highlighted the significant role of TAAR5 in the central nervous system and periphery. Beta-galactosidase mapping of TAAR5 expression showed its localization not only in the glomeruli but also in deeper layers of olfactory bulb projecting to the limbic brain olfactory circuitry. Moreover, TAAR5 knockout mice show increased adult neurogenesis and elevated number of dopamine neurons. Also, it was observed statistically significant changes in osmotic erythrocyte fragility in TAAR5-KO mice.[15]
Mutations in the TAAR5 gene were found to affect human olfaction. Icelanders with a mutation in the gene were less likely to describe fish smell containing trimethylamine as unpleasant, and described licorice odor and cinnamon odor more intensely.[16]
^"Human PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
^"Mouse PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
^Zeng Z, Fan P, Rand E, Kyaw H, Su K, Madike V, et al. (January 1998). "Cloning of a putative human neurotransmitter receptor expressed in skeletal muscle and brain". Biochemical and Biophysical Research Communications. 242 (3): 575–578. doi:10.1006/bbrc.1997.7591. PMID9464258.
^Lindemann L, Ebeling M, Kratochwil NA, Bunzow JR, Grandy DK, Hoener MC (March 2005). "Trace amine-associated receptors form structurally and functionally distinct subfamilies of novel G protein-coupled receptors". Genomics. 85 (3): 372–385. doi:10.1016/j.ygeno.2004.11.010. PMID15718104.
^Wallrabenstein I, Singer M, Panten J, Hatt H, Gisselmann G (2015). "Timberol® Inhibits TAAR5-Mediated Responses to Trimethylamine and Influences the Olfactory Threshold in Humans". PLOS ONE. 10 (12): e0144704. Bibcode:2015PLoSO..1044704W. doi:10.1371/journal.pone.0144704. PMC4684214. PMID26684881. While mice produce gender-specific amounts of urinary TMA levels and were attracted by TMA, this odor is repellent to rats and aversive to humans [19], indicating that there must be species-specific functions. ... Furthermore, a homozygous knockout of murine TAAR5 abolished the attraction behavior to TMA [19]. Thus, it is concluded that TAAR5 itself is sufficient to mediate a behavioral response at least in mice. ... Whether the TAAR5 activation by TMA elicits specific behavioral output like avoidance behavior in humans still needs to be examined.
^Khan MZ, Nawaz W (October 2016). "The emerging roles of human trace amines and human trace amine-associated receptors (hTAARs) in central nervous system". Biomedicine & Pharmacotherapy. 83: 439–449. doi:10.1016/j.biopha.2016.07.002. PMID27424325.
^Gisladottir RS, Ivarsdottir EV, Helgason A, Jonsson L, Hannesdottir NK, Rutsdottir G, et al. (December 2020). "Sequence Variants in TAAR5 and Other Loci Affect Human Odor Perception and Naming". Current Biology. 30 (23): 4643–4653.e3. Bibcode:2020CBio...30E4643G. doi:10.1016/j.cub.2020.09.012. PMID33035477. S2CID222213583.
† References for all endogenous human TAAR1 ligands are provided at List of trace amines
‡ References for synthetic TAAR1 agonists can be found at TAAR1 or in the associated compound articles. For TAAR2 and TAAR5 agonists and inverse agonists, see TAAR for references.
