Abstract
The discovery of a family of G-protein coupled receptors, some of which bind and are activated by biogenic trace amines, has prompted speculation as to the physiological role of these receptors. Observations associated with the distribution of these trace amine associated receptors (TAARs) suggest that they may be involved in depression, attention-deficit hyperactivity disorder, eating disorders, migraine headaches, and Parkinson's disease. Preliminary in vitro data, obtained using cloned receptors, also suggest a role for TAARs in the function of hallucinogens.
Keywords: Trace amine associated receptor, TAAR, mammalian, G-protein coupled receptor, ADHD, hypothyroidism-associated depression, prepulse inhibition
Full Text
The Full Text of this article is available as a PDF (184.1 KB).
References
- 1.Sabelli HC, Mosnaim AD. Phenylethylamine hypothesis of affective behavior. Am J Psychiatry. 1974;131:695–699. doi: 10.1176/ajp.131.6.695. [DOI] [PubMed] [Google Scholar]
- 2.Potkin SG, Karoum F, Chuang LW, Cannon-Spoor HE, Phillips I, Wyatt RJ. Phenylethylamine in paranoid chronic schizophrenia. Science. 1979;206:470–471. doi: 10.1126/science.504988. [DOI] [PubMed] [Google Scholar]
- 3.Davis BA, Boulton AA. The trace amines and their acidic metabolites in depression: an overview. Prog Neuropsychopharmacol Biol Psychiatry. 1994;18:17–45. doi: 10.1016/0278-5846(94)90022-1. [DOI] [PubMed] [Google Scholar]
- 4.Sandler M, Ruthven CR, Goodwin BL, Coppen A. Decreased cerebrospinal fluid concentration of free phenylacetic acid in depressive illness. Clin Chim Acta. 1979;93:169–171. doi: 10.1016/0009-8981(79)90261-4. [DOI] [PubMed] [Google Scholar]
- 5.Altar C, Wasley A, Martin L. Autoradiographic localization and pharmacology of unique 3Htryptamine binding sites in rat brain. Neuroscience. 1986;17:263–273. doi: 10.1016/0306-4522(86)90241-1. [DOI] [PubMed] [Google Scholar]
- 6.Hauger R, Skolnick P, Paul S. Specific 3Hbeta-phenylethylamine binding sites in rat brain. Eur J Pharmacol. 1982;83:147–148. doi: 10.1016/0014-2999(82)90301-6. [DOI] [PubMed] [Google Scholar]
- 7.Kellar KJ, Cascio CS. 3HTryptamine: high affinity binding sites in rat brain. Eur J Pharmacol. 1982;78:475–478. doi: 10.1016/0014-2999(82)90492-7. [DOI] [PubMed] [Google Scholar]
- 8.Perry DC. 3Htryptamine autoradiography in rat brain and choroid plexus reveals two distinct sites. J Pharmacol Exp Ther. 1986;236:548–559. [PubMed] [Google Scholar]
- 9.Ungar F, Mosnaim A, Ungar B, Wolf M. Tyramine-binding by synaptosomes from rat brain: effect of centrally active drugs. Biol Psychiatry. 1977;12:661–668. [PubMed] [Google Scholar]
- 10.Roeder T. Octopamine in invertebrates. Prog Neurobiol. 1999;59:533–561. doi: 10.1016/S0301-0082(99)00016-7. [DOI] [PubMed] [Google Scholar]
- 11.Borowsky B, Adham N, Jones KA, et al. Trace amines: identification of a family of mammalian G protein-coupled receptors. Proc Nalt Acad Sci USA. 2001;98:8966–8971. doi: 10.1073/pnas.151105198. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 12.Bunzow JR, Sonders MS, Arttmagangkul S, et al. Amphetamine, 3,4-methylenedioxymethamphetamine, lysergic acid diethylamide, and metabolites of the catecholamine neurotransmitters are agonists of a trace amine receptor. Mol Pharmacol. 2001;60:1181–1188. doi: 10.1124/mol.60.6.1181. [DOI] [PubMed] [Google Scholar]
- 13.Branchek TA, Blackburn TP. Trace amine receptors as targets for novel therapeutics: legend, myth and fact. Curr Opin Pharmacol. 2003;3:90–97. doi: 10.1016/S1471-4892(02)00028-0. [DOI] [PubMed] [Google Scholar]
- 14.Shimazu S, Miklya I. Pharmacological studies with endogenous enhancer substances: β-phenethylamine, tryptamine, and their synthetic derivatives. Prog Neuropsychopharmacol Biol Psychiatry. 2004;28:421–427. doi: 10.1016/j.pnpbp.2003.11.016. [DOI] [PubMed] [Google Scholar]
- 15.Schmidt N, Ferger B. The biogenic trace amine tyramine induces pronounced hydroxyl radical production via monoamine oxidase dependent mechanism: an in vivo microdialysis study in mouse striatum. Brain Res. 2004;1012:101–107. doi: 10.1016/j.brainres.2004.03.036. [DOI] [PubMed] [Google Scholar]
- 16.Davenport AP. Peptide and trace amine orphan receptors: prospects for new therapeutic targets. Curr Opin Pharmacol. 2003;3:127–134. doi: 10.1016/S1471-4892(03)00003-1. [DOI] [PubMed] [Google Scholar]
- 17.Berry MD. Mammalian central nervous system trace amines: pharmacologic amphetamines, physiologic neuromodulators. J Neurochem. 2004;90:257–271. doi: 10.1111/j.1471-4159.2004.02501.x. [DOI] [PubMed] [Google Scholar]
- 18.Geracitano R, Federici M, Prisco S, Bernardi G, Mercuri NB. Inhibitory effects of trace amines on rat midbrain dopaminergic neurons. Neuropharmacology. 2004;46:807–814. doi: 10.1016/j.neuropharm.2003.11.031. [DOI] [PubMed] [Google Scholar]
- 19.Lindemann L, Ebeling M, Kratochwil NA, Bunzow JR, Grandy DK, Hoener MC. Trace amine associated receptors from structurally and functionally distinct subfamilies of novel G protein-coupled receptors. Genomics. 2005;85:372–385. doi: 10.1016/j.ygeno.2004.11.010. [DOI] [PubMed] [Google Scholar]
- 20.Miller GM, Madras BK. A trace amine receptor (TAR1) is a novel amphetamine receptor in primate brain poster. Paper presented at: Sixty-fifth Annual Meeting of the College on Problems of Drug Dependence (CPDD), June 15–19, 2003; Bal Harbour, FL.
- 21.Yin T, Tu Y, Johnstone EM, Little SP. A Characterization of the Trace Amine 1 Receptor (Program No. 961.5). Paper presented at: 2004 Abstract Viewer/Itinerary Planner, 2004 Online; Washington, DC: Society for Neuroscience.
- 22.Premont RT, Gainetdinov RR, Caron MG. Following the trace of elusive amines. Proc Natl Acad Sci USA. 2001;98:9474–9475. doi: 10.1073/pnas.181356198. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 23.Duan J, Martinez M, Sanders AR, et al. Polymorphisms in the trace amine receptor 4 (TRAR4) gene on chromosome 6q23.2 are associated with susceptibility to schizophrenia. Am J Hum Genet. 2004;75:624–638. doi: 10.1086/424887. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 24.Madras BK, Verrico C, Jassen A, Miller GM. Attention Deficit Hyperactivity Disorder (ADHD): New Roles for Old Trace Amines and Monoamine Transporters poster. Paper presented at: The American College of Neuropsychopharmacology (ACNP) 43rd Annual Meeting, December 12–16, 2004; San Juan, Puerto Rico.
- 25.Grandy DK, Scanlan TS. Thyroid Hormone Metabolites and Depression: A New Twist on an Old Tale poster. Paper presented at: The American College of Neuropsychopharmacology (ACNP) 43rd Annual Meeting, December 12–16, 2004; San Juan, Puerto Rico.
- 26.Scanlan TS, Suchland KL, Hart ME, et al. 3-Iodothyronamine is an endogenous and rapid-acting derivative of thyroid hormone. Nat Med. 2004;10:638–642. doi: 10.1038/nm1051. [DOI] [PubMed] [Google Scholar]
- 27.Jones CK, Eberle EL, Shaw DB, McKinzie DL, Shannon HE. Pharmacologic interactions between the muscarinic cholinergic and dopaminergic systems in the modulation of prepulse inhibition in rats. J Pharmacol Exp Ther. 2005;312:1055–1063. doi: 10.1124/jpet.104.075887. [DOI] [PubMed] [Google Scholar]
- 28.Wolinsky TD, Swanson CJ, Zhong H, Smith KE, Branchek TA, Gerald CP. Deficit in Prepulse Inhibition and Enhanced Sensitivity to Amphetamine in Mice Lacking the Trace Amine-1 Receptor poster. Paper presented at: The American College of Neuropsychopharmacology (ACNP) 43rd Annual Meeting; December 12–16, 2004; San Juan, Puerto Rico.
- 29.Hirashima A, Pan C, Shinkai K, et al. Quantitative structure-activity studies of octopaminergic agonists and antagonists against nervous system of Locusta migratoria. Bioorg Med Chem. 1998;6:903–910. doi: 10.1016/S0968-0896(98)00024-8. [DOI] [PubMed] [Google Scholar]
- 30.Hirashima A, Nagata T, Pan C, Kuwano E, Taniguchi E, Eto M. Three-dimensional molecular field analyses of octopaminergic agonists and antagonists for the locust neuronal octopamine receptor class 3. J Mol Graph Model. 1999;17:198–218. doi: 10.1016/S1093-3263(99)00031-5. [DOI] [PubMed] [Google Scholar]
- 31.Hirashima A, Morimoto M, Kuwano E, Taniguchi E, Eto M. Three-dimensional common-feature hypotheses for octopamine agonist 2-(arylimino)imidazolidines. Bioorg Med Chem. 2002;10:117–123. doi: 10.1016/S0968-0896(01)00247-4. [DOI] [PubMed] [Google Scholar]