TY - JOUR
T1 - Trace amine-associated receptor 1-Family archetype or iconoclast?
AU - Grandy, David K.
N1 - Funding Information:
The author gratefully thanks: M.T. Ackermans, S.G. Amara, S. Arttamangkul, J. Axelrod, L.J. Braulke, J.R. Bunzow, A. Carlsson, L. Crawshaw, D.A. Crossley, II, D.C. Dawson, A. DeBarber, T. Darland, J. Douglass, K.P. Doyle, J. Faber, E. Fliers, P. Gmeiner, G. Giraud, D. Hatton, G. Heldmaier, M. Hoener, R. Hohimer, C. Jimenez, A. Kalsbeek, E. Kaufman, M. Kaufmann, T.M. Keck, M.J. Kelly, J.L. Kennedy, L.P. Klieverik, J. Köhrle, P.J. Kruzich, M. Litt, R.E. Magenis, E.K. Morris, S.B. Olson, S. Parameswaran, S.J. Patton, D.I. Quigley, N. Rediske, E.A. Reese, O. Rønnekleiv, B.L. Roth, R.B. Rothman, T.S. Scanlan, S.-L. Shyng, L.L. Simon, G. Smith, K. Smith, A. Snead, M.S. Sonders, M.P. Stenzel-Poore, K.L. Suchland, E. Tan, K. Thornburg, T.J. Visser, W. Woodward, F.-F. Yan, A. Yonkin, M. von Zastrow, G. Zhang, and R. Zucchi for thought-provoking discussions. The author is also very appreciative of the assistance received from C. Jimenez who produced the figure and A. Nilsen for assistance with depicting the structural formulae; W. Wood who helped the author search the early organic chemistry literature; and C. Lorentz who assisted the author with his translation of the original chemistry literature from German into English. Finally, the author wishes to express his heartfelt gratitude to R. Baldessarini and A.D. Mosnaim for sharing their personal recollections about the time when vertebrate non-catecholic phenylethylamines came of age. The author was supported in part by the OHSU Heart Research Center, the Methamphetamine Abuse Research Center of Portland, OR, the National Institute on Drug Abuse, and the National Institute for Mental Health. Dedicated to the memory of Einstein, the cat.
PY - 2007/12
Y1 - 2007/12
N2 - Interest has recently been rekindled in receptors that are activated by low molecular weight, noncatecholic, biogenic amines that are typically found as trace constituents of various vertebrate and invertebrate tissues and fluids. The timing of this resurgent focus on receptors activated by the "trace amines" (TA) β-phenylethylamine (PEA), tyramine (TYR), octopamine (OCT), synephrine (SYN), and tryptamine (TRYP) is the direct result of 2 publications that appeared in 2001 describing the cloning of a novel G protein-coupled receptor (GPCR) referred to by their discoverers Borowsky et al. as TA1 and Bunzow et al. as TA receptor 1 (TAR1). When heterologously expressed in Xenopus laevis oocytes and various eukaryotic cell lines, recombinant rodent and human TAR dose-dependently couple to the stimulation of adenosine 3′,5′-monophosphate (cAMP) production. Structure-activity profiling based on this functional response has revealed that in addition to the TA, other biologically active compounds containing a 2-carbon aliphatic side chain linking an amino group to at least 1 benzene ring are potent and efficacious TA receptor agonists with amphetamine (AMPH), methamphetamine, 3-iodothyronamine, thyronamine, and dopamine (DA) among the most notable. Almost 100 years after the search for TAR began, numerous TA1/TAR1-related sequences, now called TA-associated receptors (TAAR), have been identified in the genome of every species of vertebrate examined to date. Consequently, even though heterologously expressed TAAR1 fits the pharmacological criteria established for a bona fide TAR, a major challenge for those working in the field is to discern the in vivo pharmacology and physiology of each purported member of this extended family of GPCR. Only then will it be possible to establish whether TAAR1 is the family archetype or an iconoclast.
AB - Interest has recently been rekindled in receptors that are activated by low molecular weight, noncatecholic, biogenic amines that are typically found as trace constituents of various vertebrate and invertebrate tissues and fluids. The timing of this resurgent focus on receptors activated by the "trace amines" (TA) β-phenylethylamine (PEA), tyramine (TYR), octopamine (OCT), synephrine (SYN), and tryptamine (TRYP) is the direct result of 2 publications that appeared in 2001 describing the cloning of a novel G protein-coupled receptor (GPCR) referred to by their discoverers Borowsky et al. as TA1 and Bunzow et al. as TA receptor 1 (TAR1). When heterologously expressed in Xenopus laevis oocytes and various eukaryotic cell lines, recombinant rodent and human TAR dose-dependently couple to the stimulation of adenosine 3′,5′-monophosphate (cAMP) production. Structure-activity profiling based on this functional response has revealed that in addition to the TA, other biologically active compounds containing a 2-carbon aliphatic side chain linking an amino group to at least 1 benzene ring are potent and efficacious TA receptor agonists with amphetamine (AMPH), methamphetamine, 3-iodothyronamine, thyronamine, and dopamine (DA) among the most notable. Almost 100 years after the search for TAR began, numerous TA1/TAR1-related sequences, now called TA-associated receptors (TAAR), have been identified in the genome of every species of vertebrate examined to date. Consequently, even though heterologously expressed TAAR1 fits the pharmacological criteria established for a bona fide TAR, a major challenge for those working in the field is to discern the in vivo pharmacology and physiology of each purported member of this extended family of GPCR. Only then will it be possible to establish whether TAAR1 is the family archetype or an iconoclast.
KW - Iodothyronamine
KW - Mental health
KW - Noncatecholic phenylethylamines
KW - Orphan receptor
KW - Phenethylamine
KW - Psychostimulant
KW - Schizophrenia
KW - Trace amine
KW - Tyramine
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U2 - 10.1016/j.pharmthera.2007.06.007
DO - 10.1016/j.pharmthera.2007.06.007
M3 - Review article
C2 - 17888514
AN - SCOPUS:36248952213
SN - 0163-7258
VL - 116
SP - 355
EP - 390
JO - Pharmacology and Therapeutics
JF - Pharmacology and Therapeutics
IS - 3
ER -