Prostaglandin E₂ Increases the Expression of B-Type Natriuretic Peptide Receptor through EP1 Receptor, Ca²⁺ Mobilization and Protein Kinase C Signaling Pathway in Rat Calvarial Osteoblasts

Abstract

The C-type natriuretic peptide stimulates osteoblastic functions through the B-type natriuretic receptor (NPR-B). In this study, we examined the signaling pathway behind the regulation of NPR-B expression through the prostaglandin E₂ (PGE₂) receptor, EP1 subtype using rat calvarial osteoblasts. A23187 as a Ca²⁺ ionophore increased NPR-B expression dose-dependently. PGE₂ or 17-phenyl-ω-trinor PGE₂ (EP1A), an EP1 agonist, increased NPR-B expression, and the potentiating effects were blocked by treating with BAPTA-AM as an intracellular Ca²⁺ chelator. Activators of protein kinase C (PKC), 1-oleoyl-2-acetyl-sn-glycerol, a membrane-permeable diacylglycerol, and 12-o-tetradecanoyl-phorbol-13-acetate, also increased NPR-B expression, and the potentiating effects were blocked by treating with BAPTA-AM. The treatment of cells with GF109203X, a PKC inhibitor, blocked the PGE₂- and EP1A-induced increase in NPR-B expression. From these results, we concluded that EP1-mediated increase in the expression of NPR-B requires not only Ca²⁺ mobilization but also PKC activation through the activation of phosphatidylinositol-specific phospholipase C.