α2 Adrenergic Receptor Trafficking as a Therapeutic Target in Antidepressant Drug Action.

Abstract:

: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 α(2A)ARs. Our findings, as outlined herein, demonstrate that TCAs function as arrestin-biased ligands at α(2A)ARs. Importantly, TCA-induced α(2A)AR/arrestin recruitment leads to receptor endocytosis and downregulation of α(2A)AR expression with prolonged exposure. These findings represent a novel mechanism linking α(2)AR trafficking with antidepressant pharmacology.

authors

Cottingham C,Ferryman CJ,Wang Q

doi

10.1016/bs.pmbts.2015.03.007

subject

Has Abstract

pub_date

2015-01-01 00:00:00

pages

207-25

eissn

1877-1173

issn

1878-0814

pii

S1877-1173(15)00060-5

journal_volume

132

pub_type

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