Label-free optical biosensor for ligand-directed functional selectivity acting on beta(2) adrenoceptor in living cells.
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.
Fang
Ye
Y
Biochemical Technologies, Science and Technology Division, Corning Incorporated, Sullivan Park, Corning, NY 14831, USA. fangy2@corning.com
Ferrie
Ann M
AM
D058672:Adrenergic beta-2 Receptor Antagonists; D000319:Adrenergic beta-Antagonists / Q000494:pharmacology; D000420:Albuterol / Q000031:analogs & derivatives / Q000494:pharmacology; D015374:Biosensing Techniques / Q000295:instrumentation*; D002396:Catechols / Q000494:pharmacology; D002460:Cell Line; D002470:Cell Survival / Q000187:drug effects; D004837:Epinephrine / Q000494:pharmacology; D006801:Humans; D007700:Kinetics; D008024:Ligands; D055095:Optics and Photonics / Q000295:instrumentation*; D018343:Receptors, Adrenergic, beta-2 / Q000378:metabolism*; D000068299:Salmeterol Xinafoate; D015398:Signal Transduction / Q000187:drug effects
D058672:Adrenergic beta-2 Receptor Antagonists; D000319:Adrenergic beta-Antagonists; D002396:Catechols; D008024:Ligands; D018343:Receptors, Adrenergic, beta-2; D000068299:Salmeterol Xinafoate; C034221:catechol; D000420:Albuterol; D004837:Epinephrine