TY - GEN
T1 - α2 adrenergic receptor trafficking as a therapeutic target in antidepressant drug action
AU - Cottingham, Christopher
AU - Ferryman, Craig J.
AU - Wang, Qin
N1 - Publisher Copyright:
© 2015 Elsevier Inc. All rights reserved.
PY - 2015
Y1 - 2015
N2 - Antidepressant drugs remain poorly understood, especially with respect to pharmacological mechanisms of action. This lack of knowledge results from the extreme complexity inherent to psychopharmacology, as well as to a corresponding lack of knowledge regarding depressive disorder pathophysiology. While the final analysis is likely to be multifactorial and heterogeneous, compelling evidence exists for upregulation of brain α2 adrenergic receptors (ARs) in depressed patients. This evidence has sparked a line of research into actions of a particular antidepressant drug class, the tricyclic antidepressants (TCAs), as direct ligands at α2AARs. Our findings, as outlined herein, demonstrate that TCAs function as arrestin-biased ligands at α2AARs. Importantly, TCA-induced α2AAR/arrestin recruitment leads to receptor endocytosis and downregulation of α2AAR expression with prolonged exposure. These findings represent a novel mechanism linking α2AR trafficking with antidepressant pharmacology.
AB - Antidepressant drugs remain poorly understood, especially with respect to pharmacological mechanisms of action. This lack of knowledge results from the extreme complexity inherent to psychopharmacology, as well as to a corresponding lack of knowledge regarding depressive disorder pathophysiology. While the final analysis is likely to be multifactorial and heterogeneous, compelling evidence exists for upregulation of brain α2 adrenergic receptors (ARs) in depressed patients. This evidence has sparked a line of research into actions of a particular antidepressant drug class, the tricyclic antidepressants (TCAs), as direct ligands at α2AARs. Our findings, as outlined herein, demonstrate that TCAs function as arrestin-biased ligands at α2AARs. Importantly, TCA-induced α2AAR/arrestin recruitment leads to receptor endocytosis and downregulation of α2AAR expression with prolonged exposure. These findings represent a novel mechanism linking α2AR trafficking with antidepressant pharmacology.
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U2 - 10.1016/bs.pmbts.2015.03.007
DO - 10.1016/bs.pmbts.2015.03.007
M3 - Conference contribution
C2 - 26055060
AN - SCOPUS:84942194517
SN - 9780128029398
T3 - Progress in Molecular Biology and Translational Science
SP - 207
EP - 225
BT - Trafficking of GPCRs, 2015
A2 - Wu, Guangyu
PB - Elsevier B.V.
ER -