TY - JOUR
T1 - Real time differentiation of G-protein coupled receptor (GPCR) agonist and antagonist by two photon fluorescence laser microscopy
AU - Cai, Minying
AU - Stankova, Magda
AU - Pond, Stephanie J.K.
AU - Mayorov, Alexander V.
AU - Perry, Joseph W.
AU - Yamamura, Henry I.
AU - Trivedi, Dev
AU - Hruby, Victor J.
PY - 2004/6/16
Y1 - 2004/6/16
N2 - 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 β-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 β-arrestin, which has been shown to be responsible for the rapid desensitization of cAMP-signaling processes.
AB - 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 β-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 β-arrestin, which has been shown to be responsible for the rapid desensitization of cAMP-signaling processes.
UR - http://www.scopus.com/inward/record.url?scp=2942620138&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=2942620138&partnerID=8YFLogxK
U2 - 10.1021/ja049473m
DO - 10.1021/ja049473m
M3 - Article
C2 - 15186137
AN - SCOPUS:2942620138
VL - 126
SP - 7160
EP - 7161
JO - Journal of the American Chemical Society
JF - Journal of the American Chemical Society
SN - 0002-7863
IS - 23
ER -