Bradykinin Mediates Phosphorylation of eNOS in Odontoblasts

Abstract

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.

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