Cloning of a Putative Human Neurotransmitter Receptor Expressed in Skeletal Muscle and Brain

Zeng, Zhizhen; Fan, Ping; Rand, Eyal; Kyaw, Hla; Su, Kui; Madike, Victor; Carter, Kenneth C.; Li, Yang

doi:10.1006/bbrc.1997.7591

Cited by 27 publications

(21 citation statements)

References 13 publications

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“…A combined linkage and association analysis of the SCA1 (Spinocerebellar Ataxia 1; 6p23) gene has been performed in a subsample from this study, with results favouring the influence of QTLs in linkage disequilibrium with SCA1 rather than variants at SCA1 itself accounting for variance in arithmetic performance (Luciano et al, in preparation). The Schonell reading test showed linkage on 6q, with a putative neurotransmitter receptor located in this region (Zeng et al, 1998).…”

Section: Discussionmentioning

confidence: 97%

Genome-wide Scan of IQ Finds Significant Linkage to a Quantitative Trait Locus on 2q

et al. 2005

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A genome-wide linkage scan of 795 microsatellite markers (761 autosomal, 34 X chromosome) was performed on Multidimensional Aptitude Battery subtests and verbal, performance and full scale scores, the WAIS-R Digit Symbol subtest, and two word-recognition tests (Schonell Graded Word Reading Test, Cambridge Contextual Reading Test) highly predictive of IQ. The sample included 361 families comprising 2-5 siblings who ranged in age from 15.7 to 22.2 years; genotype, but not phenotype, data were available for 81% of parents. A variance components analysis which controlled for age and sex effects showed significant linkage for the Cambridge reading test and performance IQ to the same region on chromosome 2, with respective LOD scores of 4.15 and 3.68. Suggestive linkage (LOD score>2.2) for various measures was further supported on chromosomes 6, 7, 11, 14, 21 and 22. Where location of linkage peaks converged for IQ subtests within the same scale, the overall scale score provided increased evidence for linkage to that region over any individual subtest. Association studies of candidate genes, particularly those involved in neural transmission and development, will be directed to genes located under the linkage peaks identified in this study.

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Section: Discussionmentioning

confidence: 97%

Genome-wide Scan of IQ Finds Significant Linkage to a Quantitative Trait Locus on 2q

et al. 2005

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“…Liberles and Buck (2006) showed that essentially all TAARs, with the exception of TAAR1, are localized in the olfactory epithelium with little to no expression of any TAAR in the brain or other tissue of the body. This is quite surprising given that multiple labs found TAAR1 in various brain areas and in the periphery (Borowsky et al, 2001;Bunzow et al, 2001;Grandy, 2007;Lindemann et al, 2008), whereas other TAARs, such as TAAR5, TAAR6, and TAAR9, have been detected in human CNS and peripheral organs, with TAAR5 actually being found in human basal ganglia (Zeng et al, 1998;Borowsky et al, 2001). Given the fact that TA2/TAAR4 is a pseudogene in the human genome and relatively little information is currently available on the biochemistry and function of other TAARs, we will focus in this assay on the TAAR1 receptor that is relatively conserved and found in all studied species.…”

Section: Trace Amine-associated Receptorsmentioning

confidence: 96%

Trace Amine-Associated Receptors as Emerging Therapeutic Targets: TABLE 1

2009

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Endogenous trace amines (TAs) of unknown biological function are structurally related to classic monoaminergic neurotransmitters and found at low concentrations in the mammalian brain. Their recently discovered group of G protein-coupled receptors, trace amine-associated receptors (TAARs), may represent putative targets not only for trace and other amines but also for a variety of monoaminergic compounds, including amphetamines and monoamine metabolites. The trace amineassociated receptor 1 (TAAR1), which is in part associated with the monoaminergic neuronal circuitry controlling various functions, including movement, is the best characterized of the class, although little is known about its regulation and function.Here we review the pharmacology and biochemical properties of the TAAR1 and its physiological functions as revealed in studies involving knockout mice lacking this receptor. Potential therapeutic applications of future selective TAAR1 agonists and antagonists are also discussed. Although understanding of biology and functions mediated by other TAARs is still in its infancy, it is expected that further characterization of the functional roles and biochemical properties of TAARs and identification of endogenous and exogenous ligands will eventually promote these receptors as an attractive class of targets to correct monoaminergic processes that could be dysfunctional in a host of disorders of brain and periphery.

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“…In consequence, TAAR are potential new important therapeutic targets for several pathological situations [13], [14]. The first human member of this receptor group (TAAR5) was identified in 1998 [15], [16] and the term TAAR was introduced when TAAR1, TAAR8 and TAAR9 were discovered [17]. Three out of the nine hTAAR members are pseudogenes [18].…”

Section: Introductionmentioning

confidence: 99%

Differential Modulation of Beta-Adrenergic Receptor Signaling by Trace Amine-Associated Receptor 1 Agonists

et al. 2011

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Trace amine-associated receptors (TAAR) are rhodopsin-like G-protein-coupled receptors (GPCR). TAAR are involved in modulation of neuronal, cardiac and vascular functions and they are potentially linked with neurological disorders like schizophrenia and Parkinson's disease. Subtype TAAR1, the best characterized TAAR so far, is promiscuous for a wide set of ligands and is activated by trace amines tyramine (TYR), phenylethylamine (PEA), octopamine (OA), but also by thyronamines, dopamine, and psycho-active drugs. Unfortunately, effects of trace amines on signaling of the two homologous β-adrenergic receptors 1 (ADRB1) and 2 (ADRB2) have not been clarified yet in detail. We, therefore, tested TAAR1 agonists TYR, PEA and OA regarding their effects on ADRB1/2 signaling by co-stimulation studies. Surprisingly, trace amines TYR and PEA are partial allosteric antagonists at ADRB1/2, whereas OA is a partial orthosteric ADRB2-antagonist and ADRB1-agonist. To specify molecular reasons for TAAR1 ligand promiscuity and for observed differences in signaling effects on particular aminergic receptors we compared TAAR, tyramine (TAR) octopamine (OAR), ADRB1/2 and dopamine receptors at the structural level. We found especially for TAAR1 that the remarkable ligand promiscuity is likely based on high amino acid similarity in the ligand-binding region compared with further aminergic receptors. On the other hand few TAAR specific properties in the ligand-binding site might determine differences in ligand-induced effects compared to ADRB1/2. Taken together, this study points to molecular details of TAAR1-ligand promiscuity and identified specific trace amines as allosteric or orthosteric ligands of particular β-adrenergic receptor subtypes.

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Cloning of a Putative Human Neurotransmitter Receptor Expressed in Skeletal Muscle and Brain

Cited by 27 publications

References 13 publications

Genome-wide Scan of IQ Finds Significant Linkage to a Quantitative Trait Locus on 2q

Genome-wide Scan of IQ Finds Significant Linkage to a Quantitative Trait Locus on 2q

Trace Amine-Associated Receptors as Emerging Therapeutic Targets: TABLE 1

Differential Modulation of Beta-Adrenergic Receptor Signaling by Trace Amine-Associated Receptor 1 Agonists

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