Trace amine-associated receptor 2 (TAAR2), formerly known as G protein-coupled receptor 58 (GPR58), is a protein that in humans is encoded by the TAAR2gene.[5][6][7][8] TAAR2 is coexpressed with Gα proteins;[8] however, as of February 2017,[update] its signal transduction mechanisms have not been determined.[8]
Using brain histochemistry staining of mice with LacZ insertion into TAAR2 gene histochemical reaction was found in the glomerular layer of the olfactory bulb, but intensive staining was found in the deeper layer as well. The histochemical reaction was observed in the fibers of the olfactory nerve, in the glomeruli of the glomerular layer, several short axon (SA) cells (outer plexiform layer or granular layer) and neuronal projections that were visualized throughout the depth of the olfactory bulb. Furthermore, LacZ staining was observed in the limbic areas of the brain receiving olfactory input, i.e., piriform cortex molecular area, hippocampus (CA1 field, pyramidal layer), hypothalamic lateral zone (zone incerta) and lateral habenula. In addition, a histochemical reaction was found in the midbrain raphe nuclei and primary somatosensory area of the cortex (layer 5). Real-time quantitative PCR with reverse transcription confirmed TAAR2 gene expression in the mouse brain areas such as the frontal cortex, hypothalamus, and brainstem.[12][13]
Involvement in the functioning of monoamine systems
It has been found that TAAR2 knockout mice have an increased number of neuroblast-like and proliferating cells in both subventricular and subgranular zones of the dentate gyrus in comparison to wild type animals. Furthermore, TAAR2 knockout mice have an increased the brain-derived neurotrophic factor (BDNF) level in the striatum.[12]
TCells, B Cells and Peripheral Mononuclear cells express TAAR2 mRNA. Migration toward TAAR1 ligands required both TAAR1 and TAAR2 expression based on siRNA experiments.[11] In T cells, the same stimuli triggered cytokine secretion while in B cells Immunoglobulin secretion is triggered.[11]
Possible Ligands
3‐iodo‐thyronamine(T1AM) was identified as a nonselective ligand for TAAR2.[10]
Additional TAAR1 ligands, p-tyramine and Beta-phenylethylamine(2-PEA) trigger TAAR2 dependant actions, though direct binding has not been demonstrated.[11]
^"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.
^Lee DK, Lynch KR, Nguyen T, Im DS, Cheng R, Saldivia VR, et al. (February 2000). "Cloning and characterization of additional members of the G protein-coupled receptor family". Biochimica et Biophysica Acta (BBA) - Gene Structure and Expression. 1490 (3): 311–23. doi:10.1016/s0167-4781(99)00241-9. PMID10684976.
^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): 372–85. doi:10.1016/j.ygeno.2004.11.010. PMID15718104.
^ abcdeDavenport AP, Alexander S, Sharman JL, Pawson AJ, Benson HE, Monaghan AE, Liew WC, Mpamhanga C, Battey J, Benya RV, Jensen RT, Karnik S, Kostenis E, Spindel E, Storjohann L, Tirupula K, Bonner TI, Neubig R, Pin JP, Spedding M, Harmar A (25 June 2015). "TAAR2". IUPHAR/BPS Guide to PHARMACOLOGY. International Union of Basic and Clinical Pharmacology. Retrieved 22 February 2017.
^ abKhan 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.
^ abCichero E, Tonelli M (May 2017). "New insights into the structure of the trace amine-associated receptor 2: Homology modelling studies exploring the binding mode of 3-iodothyronamine". Chemical Biology & Drug Design. 89 (5): 790–796. doi:10.1111/cbdd.12903. PMID27863038. S2CID21073152.
^ abcdBabusyte A, Kotthoff M, Fiedler J, Krautwurst D (March 2013). "Biogenic amines activate blood leukocytes via trace amine-associated receptors TAAR1 and TAAR2". Journal of Leukocyte Biology. 93 (3): 387–94. doi:10.1189/jlb.0912433. PMID23315425. S2CID206996784.
† 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.
