Vascular signaling through G protein-coupled receptors: New concepts

Research output: Contribution to journalArticle

45 Scopus citations

Abstract

Purpose of review G protein-coupled receptor (GPCR) signaling machinery can serve as a direct target of reactive oxygen species (ROS), including superoxide (02-), hydrogen peroxide (H202) 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 02- 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. Recent findings 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 β-arrestin, the GPCR kinases, and dynamin, a guanosine triphosphatase responsible for endocytosis. Summary 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.

Original languageEnglish (US)
Pages (from-to)153-159
Number of pages7
JournalCurrent opinion in nephrology and hypertension
Volume18
Issue number2
DOIs
StatePublished - Mar 1 2009
Externally publishedYes

Keywords

  • Endothelial cells
  • G protein-coupled receptor
  • Nicotinamide adenine dinucleotide phosphate oxidase
  • Nitric oxide
  • Reactive oxygen species
  • Redox signaling
  • S-nitrosothiols
  • S-nitrosylation
  • Vascular smooth muscle cells

ASJC Scopus subject areas

  • Internal Medicine
  • Nephrology

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