RT Journal Article
SR Electronic
T1 Ligand-Directed Signaling: 50 Ways to Find a Lover
JF Molecular Pharmacology
JO Mol Pharmacol
FD American Society for Pharmacology and Experimental Therapeutics
SP 1097
OP 1099
DO 10.1124/mol.107.040923
VO 72
IS 5
A1 Michel, Martin C.
A1 Alewijnse, Astrid E.
YR 2007
UL http://molpharm.aspetjournals.org/content/72/5/1097.abstract
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