Novel Mammalian Catecholmine Receptor Genes and Uses
OHSU # 0557
This invention encompasses expression of the Trace Amine Associated Receptor 1 (TAAR1) receptor gene in cell culture, and an assay to determine activity of the TAAR1 receptor function in the presence of test compounds. Until now, TAAR1 proteins have been difficult to express and assay in-vitro. The clones and associated methods included in this invention offer a valuable way to test the effects of compounds on the prototypical trace amine receptor.
TAAR1 is the first member of a family of G Protein-Coupled Receptor proteins (GPCRs) known as the Trace Amine Associated Receptors (TAARs) and is active in cell signal transmission. The discovery of this new family of receptors, and the novel complement of molecules that bind TAARs, opens up completely new perspectives on the physiology and pharmacology of a variety of diseases. The prototypical TAAR, TAAR1, has a unique pharmacological profile that suggests a role in drug dependence, in particular amphetamine and methamphetamine addiction. OHSU researchers have discovered a novel endogenous ligand to TAAR1 that has demonstrated physiological effects related to temperature regulation and cardiac function, thus providing evidence of the biological significance of the TAAR1.
TAAR1 binds molecules in a class of naturally occurring chemicals, known as trace amines. At naturally low concentrations trace amines have been reported to either increase or decrease a cell’s response to different neurotransmitters. In addition, TAAR1 is activated by a variety of clinically and socially important drugs, including amphetamines, ergot derivatives and adrenaline-associated agents. Activity of TAAR1 has been linked to psychiatric conditions, such as schizophrenia and bipolar disorder.
This technology includes an otherwise difficult to express receptor gene and an associated method for screening compounds that affect cell signaling related to clinically and socially important psychiatric diseases, such as schizophrenia and bipolar disorder, and drug dependence, namely amphetamine and methamphetamine addiction.
Dr. Grandy’s training was in both microbiology and molecular biology. For the last 25 years his research has focused on the cloning and deorphanization of G protein-coupled receptors (GPCRs) and the discovery of novel ligands for these receptors.
Dr. Grandy’s group discovered and deorphanized the GPCR receptor that is now referred to as the trace amine-associated receptor (TAAR1), among other receptors, namely dopamine D2, D4 and the orphanin FQ/nociceptin receptor.During the process of extensive structure activity profiling, in collaboration with Dr. Thomas Scanlan, they predicted that novel decarboxylated derivatives of thyroid hormone, e.g. 3-iodothyronamine (T1AM), would activate TAAR1.
Lindemann L, Ebeling M, Kratochwil NA, Bunzow JR, Grandy DK, Hoener MC. “Trace amine-associated receptors form structurally and functionally distinct subfamilies of novel G protein-coupled receptors.” Genomics. 2005 Mar;85(3):372-85.
Zucchi R, Chiellini G, Scanlan TS, Grandy DK. “Trace amine-associated receptors and their ligands.” Br J Pharmacol. 2006 Dec;149(8):967-78. Epub 2006 Nov 6.
Reese EA, Bunzow JR, Arttamangkul S, Sonders MS, Grandy DK. “Trace amine-associated receptor 1 displays species-dependent stereoselectivity for isomers of methamphetamine, amphetamine, and para-hydroxyamphetamine.” J Pharmacol Exp Ther. 2007 Apr;321(1):178-86.
OHSU #0380 Putative Mammalian Catecholamine Receptor (p-Tyramine-R)(TAR)
- Mark Sonders, VIABR - L474
- James Bunzow, VI.Vollum Institute
- David Grandy, SM.Physiology & Pharmacology
- OHSU # 0380 — Putative Mammalian Catecholamine Receptor (p-Tyramine-R)(TAR)
- Biological Materials - Receptors/Targets
- Research Tools - Screening
- Biological Materials
- Research Tools
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Technology Development Manager