Functional selectivity of GPCR-directed drug action through location bias.

ABSTRACT: G-protein-coupled receptors (GPCRs) are increasingly recognized to operate from intracellular membranes as well as the plasma membrane. The β₂-adrenergic GPCR can activate G_s-linked cyclic AMP (G_s-cAMP) signaling from endosomes. We show here that the homologous human β₁-adrenergic receptor initiates an internal G_s-cAMP signal from the Golgi apparatus. By developing a chemical method to acutely squelch G-protein coupling at defined membrane locations, we demonstrate that Golgi activation contributes significantly to the overall cellular cAMP response. Golgi signaling utilizes a preexisting receptor pool rather than receptors delivered from the cell surface, requiring separate access of extracellular ligands. Epinephrine, a hydrophilic e

SUBMITTER: Irannejad R 

PROVIDER: S-EPMC5733145 | biostudies-literature | 2017 Jul

REPOSITORIES: biostudies-literature