title: Rapid increase in endothelial nitric oxide production by bradykinin is mediated by protein kinase A signaling pathway.
abstract: Bradykinin (BK) acutely increases endothelial nitric oxide (NO) production by activating endothelial NO synthase (eNOS), and this increase is in part correlated with enhanced phosphorylation/dephosphorylation of eNOS by several protein kinases and phosphatases. However, the signaling mechanisms producing this increase are still controversial. In an attempt to delineate the acute effect of BK on endothelial NO production, confluent bovine aortic endothelial cells were incubated with BK, and NO production was measured by NO-specific chemiluminescence. Significant increase in NO levels was detected as early as 1 min after BK treatment, with concomitant increase in the phosphorylation of Ser(1179) (bovine sequence) site of eNOS (eNOS-Ser(1179)). This acute effect of BK on both increases was blocked only by treatment of protein kinase A inhibitor H-89, but not by the inhibitors of calmodulin-dependent kinase II and protein kinase B, suggesting that the rapid increase in NO production by BK is mediated by the PKA-dependent phosphorylation of eNOS-Ser(1179).
authors.affiliation: Department of Biomedical Sciences, National Institute of Health, 5 Nokbun-dong, Eunpyung-gu, Seoul 122-701, South Korea.
authors.forename: Sung Won
authors.initials: SW
authors.lastname: Bae
authors.forename: Hye Sue
authors.initials: HS
authors.lastname: Kim
authors.forename: Young Nam
authors.initials: YN
authors.lastname: Cha
authors.forename: Yoon Shin
authors.initials: YS
authors.lastname: Park
authors.forename: Sangmee Ahn
authors.initials: SA
authors.lastname: Jo
authors.forename: Inho
authors.initials: I
authors.lastname: Jo
mesh_terms: D000818:Animals; D001011:Aorta / Q000166:cytology; D015153:Blotting, Western; D001920:Bradykinin / Q000378:metabolism*; D002417:Cattle; D002478:Cells, Cultured; D017868:Cyclic AMP-Dependent Protein Kinases / Q000378:metabolism*; D004727:Endothelium / Q000378:metabolism*; D004730:Endothelium, Vascular / Q000166:cytology; D004791:Enzyme Inhibitors / Q000494:pharmacology; D007546:Isoquinolines / Q000494:pharmacology; D008163:Luminescent Measurements; D009569:Nitric Oxide / Q000096:biosynthesis*; D019001:Nitric Oxide Synthase / Q000378:metabolism; D052250:Nitric Oxide Synthase Type III; D010766:Phosphorylation; D015398:Signal Transduction; D013449:Sulfonamides; D013997:Time Factors
chemical_list: D004791:Enzyme Inhibitors; D007546:Isoquinolines; D013449:Sulfonamides; D009569:Nitric Oxide; D019001:Nitric Oxide Synthase; D052250:Nitric Oxide Synthase Type III; D017868:Cyclic AMP-Dependent Protein Kinases; C063509:N-(2-(4-bromocinnamylamino)ethyl)-5-isoquinolinesulfonamide; D001920:Bradykinin