Ligand-directed signaling: 50 ways to find a lover - PubMed (original) (raw)
Comment
doi: 10.1124/mol.107.040923. Epub 2007 Aug 23.
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- PMID: 17717108
- DOI: 10.1124/mol.107.040923
Comment
Ligand-directed signaling: 50 ways to find a lover
Martin C Michel et al. Mol Pharmacol. 2007 Nov.
Abstract
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 beta(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.
Comment on
- Ligand-directed signaling at the beta3-adrenoceptor produced by 3-(2-Ethylphenoxy)-1-[(1,S)-1,2,3,4-tetrahydronapth-1-ylamino]-2S-2-propanol oxalate (SR59230A) relative to receptor agonists.
Sato M, Horinouchi T, Hutchinson DS, Evans BA, Summers RJ. Sato M, et al. Mol Pharmacol. 2007 Nov;72(5):1359-68. doi: 10.1124/mol.107.035337. Epub 2007 Aug 23. Mol Pharmacol. 2007. PMID: 17717109
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