PT  - JOURNAL ARTICLE
AU  - Michel, Martin C.
AU  - Alewijnse, Astrid E.
TI  - Ligand-Directed Signaling: 50 Ways to Find a Lover
AID  - 10.1124/mol.107.040923
DP  - 2007 Nov 01
TA  - Molecular Pharmacology
PG  - 1097--1099
VI  - 72
IP  - 5
4099  - http://molpharm.aspetjournals.org/content/72/5/1097.short
4100  - http://molpharm.aspetjournals.org/content/72/5/1097.full
SO  - Mol Pharmacol2007 Nov 01; 72
AB  - In contrast to earlier concepts, it seems 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. (p. 1359) extend this concept to β3-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. The American Society for Pharmacology and Experimental Therapeutics