Amphetamines signal through intracellular TAAR1 receptors coupled to Gα₁₃ and Gα_S in discrete subcellular domains.

ABSTRACT: The extensive use of amphetamines to treat attention deficit hyperactivity disorders in children provides a compelling rationale for understanding the mechanisms of action of amphetamines and amphetamine-related drugs. We have previously shown that acute amphetamine (AMPH) regulates the trafficking of both dopamine and glutamate transporters in dopamine neurons by increasing activation of the small GTPase RhoA and of protein kinase A. Here we demonstrate that these downstream signaling events depend upon the direct activation of a trace amine-associated receptor, TAAR1, an intracellular G-protein coupled receptor (GPCR) that can be activated by amphetamines, trace amines, and biogenic amine metabolites. Using cell lines and mouse lines in which TAAR1 expression has been disrupted, we demon

SUBMITTER: Underhill SM 

PROVIDER: S-EPMC7038576 | biostudies-literature | 2021 Apr

REPOSITORIES: biostudies-literature