Everything You Always Wanted to Know about β3-AR * (* But Were Afraid to Ask)

Abstract

The beta-3 adrenergic receptor (β₃-AR) is by far the least studied isotype of the beta-adrenergic sub-family. Despite its study being long hampered by the lack of suitable animal and cellular models and inter-species differences, a substantial body of literature on the subject has built up in the last three decades and the physiology of β₃-AR is unraveling quickly. As will become evident in this work, β₃-AR is emerging as an appealing target for novel pharmacological approaches in several clinical areas involving metabolic, cardiovascular, urinary, and ocular disease. In this review, we will discuss the most recent advances regarding β₃-AR signaling and function and summarize how these findings translate, or may do so, into current clinical practice highlighting β₃-AR's great potential as a novel therapeutic target in a wide range of human conditions.

Keywords: G-protein coupled receptors; beta-3 adrenergic receptor; therapeutic target.

Figure 1

Graphic summary of β₃-AR localization. Pathways that have been studied and reported in human tissue/cell lines are in yellow boxes. Pathways studied in mouse but not yet found in humans are in blue boxes. *Alternative cAMP-independent pathway. Trp, tryptophan; 5-HT, 5-hydroxytryptamine; MAPK, mitogen-activated protein kinase; MMPs, metalloproteinases, PKG, protein kinase G; NO, nitric oxide; PKA, protein kinase A.