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A Rapid Functional Assay for the Human Trace Amine-Associated Receptor 1 Based on the Mobilization of Internal Calcium

Center for Organic and Medicinal Chemistry, RTI International, Research Triangle Park, North Carolina

Brian P. Gilmour

Center for Organic and Medicinal Chemistry, RTI International, Research Triangle Park, North Carolina

Anita H. Lewin

Center for Organic and Medicinal Chemistry, RTI International, Research Triangle Park, North Carolina

The molecular targets for trace amines (TAs) such as p-tyramine and ß-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_s-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, G₁₆, 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 G₁₆.

Key Words: human • trace amine • calcium mobilization • G16

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