title: Real time differentiation of G-protein coupled receptor (GPCR) agonist and antagonist by two photon fluorescence laser microscopy.
abstract: Receptor-based signaling mechanisms are the primary source of cellular regulation. The superfamily of G protein-coupled receptors (GPCR) is the largest and most ubiquitous of the receptor-mediated processes. Desensitization of G-protein-coupled receptors is a fundamental mechanism regulating the cellular response to agonists. We have recently studied the agonist and antagonist of the human melanocortin receptors (hMC1, hMC3, hMC4, and hMC5 receptors), the human delta opioid receptor, and the human gluacagon receptor with the help of synthetic fluorescent labeled ligands and fluorescent protein-labeled beta-arrestin-receptors that shed new insight on cellular signaling and rapid screening of drugs in real time. It was demonstrated that stimulation of these receptors by the cognate agonist triggers the rapid internalization of ligand-receptor complexes, while the interaction of the receptor with antagonists does not follow this pathway. Furthermore, receptor internalization is dependent upon beta-arrestin, which has been shown to be responsible for the rapid desensitization of cAMP-signaling processes.
authors.affiliation: Department of Chemistry, University of Arizona, 1306 East University, Tucson, Arizona 85721, USA.
authors.forename: Minying
authors.initials: M
authors.lastname: Cai
authors.forename: Magda
authors.initials: M
authors.lastname: Stankova
authors.forename: Stephanie J K
authors.initials: SJ
authors.lastname: Pond
authors.forename: Alexander V
authors.initials: AV
authors.lastname: Mayorov
authors.forename: Joseph W
authors.initials: JW
authors.lastname: Perry
authors.forename: Henry I
authors.initials: HI
authors.lastname: Yamamura
authors.forename: Dev
authors.initials: D
authors.lastname: Trivedi
authors.forename: Victor J
authors.initials: VJ
authors.lastname: Hruby
mesh_terms: D002460:Cell Line; D006801:Humans; D009074:Melanocyte-Stimulating Hormones / Q000737:chemistry / Q000494:pharmacology*; D018613:Microscopy, Confocal; D036641:Microscopy, Fluorescence, Multiphoton; D015394:Molecular Structure; D044101:Receptors, Melanocortin / Q000819:agonists* / Q000037:antagonists & inhibitors* / Q000378:metabolism; D012235:Rhodamines / Q000737:chemistry
chemical_list: D044101:Receptors, Melanocortin; D012235:Rhodamines; D009074:Melanocyte-Stimulating Hormones