International Union of Basic and Clinical Pharmacology. Guidelines for
GPCR ligand bias
Abstract
G protein-coupled receptors modulate a plethora of physiological
processes and mediate the effects of one-third of FDA-approved drugs.
Notably, depending on which ligand has activated a particular receptor,
it can engage different intracellular transducers. This paradigm of
ligand-dependent ‘biased signaling’ dictates a need to advance beyond
the level of receptors to consider the combined ligand-receptor pair in
order to understand physiological signaling. Bias signaling also has the
potential to improve medicines by reducing adverse effects. However,
this is challenged by inconsistent interpretation of results and lack of
commonly agreed guidelines. Here, we present recommended terminology and
guidelines to conduct, report and quantify bias in a comparable and
reproducible fashion. We expect these recommendations will facilitate a
common understanding of experiments and findings across basic receptor
research and drug discovery, while the area and the analytical methods
to measure bias are still evolving, especially in complex cellular,
tissue and organismal systems.