Label-free optical biosensor for ligand-directed functional selectivity acting on β2 adrenoceptor in living cells

被引：64
作者：
Fang, Ye [1 ]
Ferrie, Ann M. [1 ]
机构：
[1] Corning Inc, Biochem Technol Sci & Technol Div, Corning, NY 14831 USA
来源：
FEBS LETTERS | 2008年 / 582卷 / 05期
关键词：
optical biosensor; G protein-coupled receptor; beta(2)-adrenoceptor; ligand-directed functional selectivity;
D O I：
10.1016/j.febslet.2008.01.021
中图分类号：
Q5 [生物化学]; Q7 [分子生物学];
学科分类号：
071010 ; 081704 ;
摘要：
Recent realization of ligand-directed functional selectivity demands high-resolution tools for studying receptor biology and ligand pharmacology. Here we use label-free optical biosensor to examine the dynamic mass redistribution of human epidermoid A431 cells in response to diverse beta(2)-adrenoceptor ligands. Multi-parameter analysis reveals distinct patterns in activation and signaling of the receptor induced by different agonists. Sequential and co-stimulation assays categorize various ligands for their ability to modulate signaling induced by catechol, a structural component of catecholamines. This study documents multiple ligand-specific states of the beta(2)-adrenoceptor and highlights the power of the biosensor assays for screening pathway-biased ligands. (C) 206 Federation of European Biochemical Societies. Published by Elsevier B.V. All rights reserved.
引用
收藏
页码：558 / 564
页数：7
相关论文
共 28 条
[11]   Non-invasive optical biosensor for probing cell signaling [J].
Fang, Ye .
SENSORS, 2007, 7 (10) :2316-2329
[12]  
Fang Ye, 2007, Journal of Pharmacological and Toxicological Methods, V55, P314, DOI 10.1016/j.vascn.2006.11.001
[13]  
Fang Y, 2006, BIOPHYS J, V91, P1925, DOI [10.1529/biophysj.105.077818, 10.1529/biophysj.105.007818]
[14]   The evasive nature of drug efficacy:: implications for drug discovery [J].
Galandrin, Segolene ;
Oligny-Longpre, Genevieve ;
Bouvier, Michel .
TRENDS IN PHARMACOLOGICAL SCIENCES, 2007, 28 (08) :423-430
[15]   Biochemical and pharmacological control of the multiplicity of coupling at G-protein-coupled receptors [J].
Hermans, E .
PHARMACOLOGY & THERAPEUTICS, 2003, 99 (01) :25-44
[16]   New concepts in drug discovery: Collateral efficacy and permissive antagonism [J].
Kenakin, T .
NATURE REVIEWS DRUG DISCOVERY, 2005, 4 (11) :919-927
[17]   Transduction of receptor signals by β-arrestins [J].
Leftowitz, RJ ;
Shenoy, SK .
SCIENCE, 2005, 308 (5721) :512-517
[18]   Synergistic contributions of the functional groups of epinephrine to its affinity and efficacy at the β2 adrenergic receptor [J].
Liapakis, G ;
Chan, WC ;
Papadokostaki, M ;
Javitch, JA .
MOLECULAR PHARMACOLOGY, 2004, 65 (05) :1181-1190
[19]   GPCR functional selectivity has therapeutic impact [J].
Mailman, Richard B. .
TRENDS IN PHARMACOLOGICAL SCIENCES, 2007, 28 (08) :390-396
[20]   High-content assays for ligand regulation of G-protein-coupled receptors [J].
Milligan, G .
DRUG DISCOVERY TODAY, 2003, 8 (13) :579-585
123