Mouse Taar1 blocking peptide

Trace-amines (TAs) are endogenous amines that are implicated in several physiological processes including modulation of aminergic neurotransmission. These compounds exert their effect by activating a class of G protein-coupled receptors termed Trace-Amine Associated Receptors (TAARs), where TAAR1 is the only human receptor that has been shown to bind endogenous TAs. Most of the studies have focused on studying the role of TAAR1 on modulation of the dopamine transmission. These studies indicate that TAAR1 is a negative regulator of dopamine transmission making TAAR1 a novel target for neuropsychiatric disorders that arises from dopamine dysfunction such as schizophrenia. This review discusses the unique pharmacology of TAAR1 with the major focus on the physiological role of TAAR1 and its modulation of dopamine transmission. (C) 2015 Elsevier B.V. All rights reserved.

The molecular targets for trace amines (TAs) such as p-tyramine and beta-phenylethylamine have been recently discovered and have been shown to comprise a family of G-protein-coupled receptors based on DNA sequence homologies. These have been termed trace amine-associated receptors (TAARs) because TAs do not activate all of the identified receptors. Because TA may be involved in modulating a variety of behaviors including mood, cognition, and addiction, it is of interest to discover novel ligands for TAARs to probe the role TAs play in brain function. Pharmacophore development for the G(5)-coupled human TAAR1 (hTAAR1) would be aided by a rapid functional assay amenable to screening libraries of compounds. Accordingly, the authors used RD-HGA16 CHO-1 cells from Molecular Devices, which stably express the promiscuous G(q), G(alpha 16), to create a cell line stably expressing hTAAR1, thereby coupling receptor activation to the mobilization of internal calcium. They used this cell line to develop a homogenous fluorometric imaging plate reader-based assay using the Calcium 3 fluorescent dye. The EC50 and E-max data obtained for known TAs are in close agreement with previous work using transient hTAAR1 expression systems or a chimeric receptor. These data indicate that the hTAAR1 retains its reported pharmacological characteristics when coupled to G(alpha 16).