Bradykinin mediates phosphorylation of eNOS in odontoblasts.
While the activation of eNOS by Akt/PKB-dependent phosphorylation, leading to NO release, and the inhibition of enzyme activity by bradykinin (BK)-mediated phosphorylation of eNOS in endothelial cells are established, the phosphorylation of eNOS in odontoblasts is unknown. To clarify the regulation of eNOS in odontoblasts by BK, we examined the phosphorylation of eNOS, Akt/PKB, and ERK1/2 in odontoblasts of rat molars. BK (10(-7) M) transiently induced the phosphorylation of eNOS at Ser1177, Akt/PKB in odontoblasts, while it induced the phosphorylation of eNOS at Thr495 throughout the entire period of BK treatment. BK receptor 2 antagonist HOE 140 (10(-6) M) significantly reduced signal intensities of phosphorylated-eNOS at Ser1177, Thr495, and phosphorylated-Akt/PKB. These results suggest that BK has dual effects on the activation of eNOS in odontoblasts, the Akt/PKB-dependent up-regulation of eNOS by the transient phosphorylation at Ser1177, and the ERK1/2-independent down-regulation of eNOS by the phosphorylation at Thr495.
Korkmaz
Y
Y
Department of Operative and Preventive Dentistry and Endodontics, Heinrich-Heine-University, Moorenstr. 5, 40225 Düsseldorf, Germany. yueksel.korkmaz@uni-duesseldorf.de
Bloch
W
W
Steinritz
D
D
Baumann
M A
MA
Addicks
K
K
Schneider
K
K
Raab
W H-M
WH
D000818:Animals; D001920:Bradykinin / Q000031:analogs & derivatives / Q000378:metabolism* / Q000494:pharmacology; D065168:Bradykinin Receptor Antagonists; D015536:Down-Regulation; D004789:Enzyme Activation / Q000187:drug effects; D020536:Enzyme Activators / Q000494:pharmacology; D005455:Fluorescent Antibody Technique; D007150:Immunohistochemistry; D008297:Male; D018613:Microscopy, Confocal; D048052:Mitogen-Activated Protein Kinase 3 / Q000378:metabolism; D052250:Nitric Oxide Synthase Type III / Q000378:metabolism*; D009804:Odontoblasts / Q000378:metabolism*; D010766:Phosphorylation; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar; D012694:Serine / Q000378:metabolism; D013912:Threonine / Q000378:metabolism; D015854:Up-Regulation
D065168:Bradykinin Receptor Antagonists; D020536:Enzyme Activators; D013912:Threonine; D012694:Serine; C065679:icatibant; D052250:Nitric Oxide Synthase Type III; D051057:Proto-Oncogene Proteins c-akt; D048052:Mitogen-Activated Protein Kinase 3; D001920:Bradykinin