Trace amine-associated receptor 1 (TAAR1)

Trace amine-associated receptor 1 (TAAR1) is a protein that in humans is encoded by the TAAR1 gene. It is an amine-activated Gs-coupled and Gq-coupled G protein-coupled receptor (GPCR). It plays a significant role in regulating neurotransmission in dopamine, norepinephrine, and serotonin neurons in the CNS. It also affects immune system and neuroimmune system function through different mechanisms.

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1043491-54-8
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Background


An Overview of Trace amine-associated receptor 1 (TAAR1)

In 2001, two independent research groups, Borowski et al. and Bunzow et al., firstly discovered trace amine related receptor 1 (TAAR1), which is a trace amine related receptor (TAAR) protein encoded by the TAAR1 gene of humans beings. The structure of TAAR1 is similar to the A-type rhodopsin GPCR subfamily, which has seven transmembrane domains with short N and C terminal extensions. TAAR1 is an intracellular amine-activated Gs-coupled and Gq-coupled G-protein coupled receptor (GPCR). TAAR1 is expressed mainly in the intracellular environment of the presynaptic plasma membrane of several peripheral organs and cells, astrocytes, and monoamine neurons in the central nervous system. TAAR1 plays an important role in regulating the neurotransmission of dopamine, norepinephrine and serotonin neurons in the central nervous system (CNS). In addition, TAAR1 affects the immune system and neuroimmune system function. TAAR1 has a high affinity for amphetamine, methamphetamine, dopamine and trace amines, mediating some of its cellular effects in monoamine neurons in the CNS.

TAAR1 and diseases

It has been reported that low phenethylamine in the brain is associated with disease. Major depression is associated with a low concentration of phenethylamine, and schizophrenia is associated with a high concentration of phenethylamine. Low phenethylamine levels and low activation of TAAR1 can cause attention deficit hyperactivity disorder. Insufficient levels of phenylethylamine lead to inactivation of the transporter TAAR1 and excess monoamine uptake, which may lead to depression. TAAR1 selective ligands may be used in the treatment of addiction to psychostimulants such as cocaine, amphetamine, and methamphetamine. Therefore, TAAR1 has great clinical significance in neurological diseases and will potentially be a biological target for the treatment of obesity and diabetes.

Inhibition of TAAR1

Trace amines, thyronamines, amiodarone derivatives and benzofurans are some specific agonists of TAAR1. Human trace amines include synephrine, phenethylamine, tryptamine, tyramine, m-methylamine, N-methyltyramine, N-methylphenethylamine, p-octopamine, and m-octylamine. 3-iodothyronamine (T1AM) is the most potent TAAR1 agonist ever discovered. The development of drugs based on TAAR1 will provide new targets for neurological disease, obesity and diabetes.

References:

Aaron, N. S., Motonori, M., Edwin, S. T., Thomas, S. S. (2008) Trace amine-associated receptor 1 (TAAR1) is activated by amiodarone metabolites. Bioorg. Med. Chem. Lett. 18: 5920–5922.