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This Article Accepted manuscript (PDF) All Versions of this Article: JOE-08-0551v1 201/2/287    most recent Alert me when this article is cited Alert me if a correction is posted Services Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via Google Scholar Google Scholar Articles by Kita, S. Articles by Yamada, Y. Search for Related Content PubMed PubMed Citation Articles by Kita, S. Articles by Yamada, Y.

S Kita, Pharmacology Research Laboratories I, Takeda Pharmaceutical Company limited, Osaka, 532-8686, Japan
I Shimomura, Department of Metabolic Medicine, Graduate School of Medicine, Osaka University, Osaka, Japan
H Nishizawa, Department of Metabolic Medicine, Graduate School of Medicine, Osaka University, Osaka, Japan
Y Okuno, Department of Metabolic Medicine, Graduate School of Medicine, Osaka University, Osaka, Japan
M Tanaka, Department of Medicine and Pathophysiology, Graduate School of Frontier Bioscience, Osaka University, Osaka, Japan
A Yasui, Department of Medicine and Pathophysiology, Graduate School of Frontier Bioscience, Osaka University, Osaka, Japan
M Matsuda, Department of Metabolic Medicine, Graduate School of Medicine, Osaka University, Osaka, Japan
Y Yamada, Pharmacology Research Laboratories I, Takeda Pharmaceutical Company limited, Osaka, Japan

Correspondence: Shunbun Kita, Email: Kita_Shunbun{at}takeda.co.jp

Abstract

Musclin is a novel skeletal muscle-derived secretory factor that was isolated by our group. Musclin contains a region homologous to natriuretic peptides. This study investigated the interaction between musclin and NP receptors. Musclin specifically bound to natriuretic peptide receptor 3, but not to natriuretic peptide receptor 1 or natriuretic peptide receptor 2. Musclin and atrial natriuretic peptide competed for binding to natriuretic peptide receptor 3. We conducted binding assays using various synthetic musclin peptides and mutant musclin proteins. The first natriuretic peptide-homologous region in musclin (88LDRL91) and the second homologous region (117MDRI120) were responsible cooperatively for high-affinity binding to natriuretic peptide receptor 3. The first natriuretic peptide-homologous region was more importantly associated with binding to natriuretic peptide receptor 3, than the second homologous region. The competitive nature of musclin with atrial natriuretic peptide for the natriuretic clearance receptor natriuretic peptide receptor 3 was also confirmed in vivo. We conclude that musclin binds to natriuretic peptide receptor 3 competitively with atrial natriuretic peptide and may affect atrial natriuretic peptide concentrations in local or systemic manner.