Differential regulation of inducible and endothelial nitric oxide synthase by kinin B1 and B2 receptors.
Kinins are vasoactive peptides that play important roles in cardiovascular homeostasis, pain and inflammation. After release from their precursor kininogens, kinins or their C-terminal des-Arg metabolites activate two distinct G protein-coupled receptors (GPCR), called B2 (B2R) or B1 (B1R). The B2R is expressed constitutively with a wide tissue distribution. In contrast, the B1R is not expressed under normal conditions but is upregulated by tissue insult or inflammatory mediators. The B2R is considered to mediate many of the acute effects of kinins while the B1R is more responsible for chronic responses in inflammation. Both receptors can couple to Galphai and Galphaq families of G proteins to release mediators such as nitric oxide (NO), arachidonic acid, prostaglandins, leukotrienes and endothelium-derived hyperpolarizing factor and can induce the release of other inflammatory agents. The focus of this review is on the different transduction events that take place upon B2R and B1R activation in human endothelial cells that leads to generation of NO via activation of different NOS isoforms. Importantly, B2R-mediated eNOS activation leads to a transient ( approximately 5min) output of NO in control endothelial cells whereas in cytokine-treated endothelial cells, B1R activation leads to very high and prolonged ( approximately 90min) NO production that is mediated by a novel signal transduction pathway leading to post-translational activation of iNOS.
Kuhr
F
F
Department of Pharmacology, University of Illinois at Chicago, College of Medicine, 835 South Wolcott, (M/C 868), Chicago, IL 60612, United States.
Lowry
J
J
Zhang
Y
Y
Brovkovych
V
V
Skidgel
R A
RA
D042783:Endothelial Cells / Q000378:metabolism*; D006801:Humans; D052247:Nitric Oxide Synthase Type II / Q000378:metabolism*; D052250:Nitric Oxide Synthase Type III / Q000378:metabolism*; D043783:Receptor, Bradykinin B1 / Q000378:metabolism*; D043782:Receptor, Bradykinin B2 / Q000378:metabolism*; D015398:Signal Transduction / Q000502:physiology
D043783:Receptor, Bradykinin B1; D043782:Receptor, Bradykinin B2; D052247:Nitric Oxide Synthase Type II; D052250:Nitric Oxide Synthase Type III