Vascular signaling through G protein-coupled receptors: new concepts.
OBJECTIVE
G protein-coupled receptor (GPCR) signaling machinery can serve as a direct target of reactive oxygen species (ROS), including superoxide (O2-), hydrogen peroxide (H2O2) as well as reactive nitrogen species, including nitric oxide and S-nitrosothiols (SNOs). Nicotinamide adenine dinucleotide phosphate (NADPH) oxidase is one of the major sources of O2- produced following GPCR activation in vasculature. Nitric oxide is generated by three isoforms of nitric oxide synthase (NOS). This review will summarize the recent progress on GPCR signaling modulation by NADPH oxidase-derived ROS and NOS-derived SNOs.


RESULTS
ROS and reactive nitrogen species play an important role in GPCR signaling involved in various physiological functions such as cell growth, migration, gene expression as well as pathophysiologies. NADPH oxidase-derived ROS activate specific redox signaling events involved in cardiovascular diseases. SNOs can modulate GPCR signaling and internalization through S-nitrosylation of the scaffolding protein beta-arrestin, the GPCR kinases, and dynamin, a guanosine triphosphatase responsible for endocytosis.


CONCLUSIONS
NADPH oxidase-derived ROS and NOS-derived SNOs are now recognized as important second messengers to regulate GPCR signaling, thereby contributing to various biological and pathophysiological functions. Understanding the molecular mechanism of how ROS, nitric oxide, and SNOs might modulate GPCR signaling is essential for development of novel therapeutic approaches.
Ushio-Fukai
Masuko
M
Department of Pharmacology, Center for Lung and Vascular Biology, Center for Cardiovascular Research, University of Illinois at Chicago, Chicago, Illinois 60612, USA. mfukai@uic.edu
D000818:Animals; D019390:Arrestins / Q000378:metabolism; D034281:Dynamins / Q000378:metabolism; D054769:G-Protein-Coupled Receptor Kinase 2 / Q000378:metabolism; D006801:Humans; D009131:Muscle, Smooth, Vascular / Q000166:cytology / Q000502:physiology*; D019001:Nitric Oxide Synthase / Q000502:physiology; D017382:Reactive Oxygen Species / Q000378:metabolism; D044140:Receptor, Angiotensin, Type 1 / Q000502:physiology; D043562:Receptors, G-Protein-Coupled / Q000502:physiology*; D026403:S-Nitrosothiols / Q000378:metabolism; D015398:Signal Transduction / Q000502:physiology*; D000071557:beta-Arrestins
D019390:Arrestins; D017382:Reactive Oxygen Species; D044140:Receptor, Angiotensin, Type 1; D043562:Receptors, G-Protein-Coupled; D026403:S-Nitrosothiols; D000071557:beta-Arrestins; D019001:Nitric Oxide Synthase; C496567:GRK2 protein, human; D054769:G-Protein-Coupled Receptor Kinase 2; D034281:Dynamins