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J.Health Sci., 55(2), 226-232, 2009
Prostaglandin E2 Enhances B-Type Natriuretic Peptide Receptor Expression in Calvarial Osteoblasts through EP1 Subtype of Prostaglandin E2 Receptor
Hiroyuki Kaneki,*, a Maki Kurokawa-Nagai,a
Yuri Sugano,a Gaku Ishi-i,a
Minoru Kurokawa,b and Hayao Idea
aFaculty of Pharmaceutical Sciences, Toho University, 2-2-1 Miyama, Funabashi, Chiba 274-8510, Japan and
bDepartment of Pharmacy, University of Toho Medical Center, Omori Hospital, 6-11-1 Omori-Nishi, Ota-ku, Tokyo 143-8541, Japan
The B-type natriuretic peptide receptor (NPR-B) is a specific receptor for the C-type natriuretic peptide (CNP) and the binding of the peptide to NPR-B stimulates the bone formation by osteoblasts. However, the mechanism behind the regulation of NPR-B expression in osteoblasts remains unknown. In this study, we examined the role of prostaglandin E2 (PGE2) through the PGE2 receptor subtypes, EP1, EP2, EP3 and EP4, in the regulation of NPR-B expression using calvarial osteoblasts from rats of various ages. Reverse Transcription-PCR (RT-PCR) and Western blotting analyses revealed that PGE2 or 17-phenyl-ω-trinor PGE2, an EP1 agonist, increased the expression of NPR-B of calvarial osteoblasts from 25-week-old rats in a time- and dose-dependent manner. The PGE2- and EP1 agonist-induced increase in NPR-B expression was blocked by treating with SC19220, an EP1 antagonist. By contrast, agonists for EP2, EP3, and EP4 failed to affect the NPR-B expression. The basal mRNA level of NPR-B and EP1 continuously decreased with the age of cell donors between 10 to 60 weeks and remained constant over 60 weeks. The degree of EP1 agonist-induced increase in NPR-B mRNA level gradually decreased with age of cell donors between 10 to 60 weeks, and no significant effect of EP1 agonist on the NPR-B mRNA level was observed over 60 weeks. From these results, we concluded that PGE2 acts as a regulator of NPR-B expression through the EP1 receptor in osteoblasts and age-related decrease in EP1 expression causes a decrease in NPR-B expression.
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