Received for publication August 15, 2007.
Revised August 20, 2007.
Accepted for publication August 21, 2007.

Ligand-directed signaling: 50 ways to find a lover (Relates to article by Sato et al., Fast Forward 23 Aug 2007)

Abstract

In contrast to earlier concepts, it appears that distinct ligands acting on the same receptor may elicit qualitative different response patterns, a phenomenon given many names including "functional selectivity," "agonist-directed trafficking," "biased agonism," &"protean agonism" or "ligand-directed signaling." In this issue of Molecular Pharmacology Sato et al. extend this concept to ₃-adrenergic receptors and report that distinct ligands can activate a single distal response via different signaling pathways. Moreover, they demonstrate that expression density can affect how distinct ligands acting on the same receptor differentially induce cellular responses. We discuss the underlying concepts for such findings and their implications for drug discovery.

Key words: Adrenergic, G protein regulation