Prostaglandin E sub(2) Increases the Expression of B-Type Natriuretic Peptide Receptor through EP1 Receptor, Ca super(2+) Mobilization and Protein Kinase C Signaling Pathway in Rat Calvarial Osteoblasts

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 E sub(2) (PGE sub(2)) receptor, EP1 subtype using rat calvarial osteoblasts. A23187 as a Ca super(2+) ionophore increased NPR-B expression dose-dependently. PGE sub(2) or 17-phenyl- omega -trinor PGE sub(2) (EP1A), an EP1 agonist, increased NPR-B expression, and the potentiating effects were blocked by treating with BAPTA-AM as an intracellular Ca super(2+) 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 PGE sub(2)- 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 Ca super(2+) mobilization but also PKC activation through the activation of phosphatidylinositol-specific phospholipase C.