Genetic models reveal that brain natriuretic peptide can signal through different tissue-specific receptor-mediated pathways

H. Chusho, Y. Ogawa, N. Tamura, M. Suda, A. Yasoda, T. Miyazawa, I. Kishimoto, Y. Komatsu, H. Itoh, K. Tanaka, Y. Saito, D. L. Garbers, K. Nakao

研究成果: ジャーナルへの寄稿学術誌査読

35 被引用数 (Scopus)

抄録

Brain natriuretic peptide (BNP), a hormone produced primarily by the cardiac ventricle, is thought to be involved in a variety of homeostatic processes through its cognate receptor, guanylyl cyclase A (GC-A). We previously created transgenic mice overexpressing BNP under the control of the liver-specific human serum amyloid P component promoter (BNP-transgenic mice) and demonstrated that they exhibit reduced blood pressure and cardiac weight accompanied by an elevation of plasma cGMP concentrations and marked skeletal overgrowth through the activation of endochondral ossification. To address whether BNP exerts its biological effects solely through GC-A, we produced BNP-transgenic mice lacking GC-A (BNP-Tg/GC-A(-/-) mice) and examined their cardiovascular and skeletal phenotypes. The GC-A(-/-) mice are hypertensive with cardiac hypertrophy relative to wild-type littermates, which is not alleviated by overexpression of BNP in BNP-Tg/GC-A(-/-) mice. The BNP-Tg/GC-A(-/-) mice, however, continue to exhibit marked longitudinal growth of vertebrae and long bones comparably to BNP-Tg mice. This study provides genetic evidence that BNP reduces blood pressure and cardiac weight through GC-A, whereas it dramatically alters endochondral ossification in the absence of this receptor. Therefore, the BNP-Tg/GC-A(-/-) mice provide the first experimental model demonstrating that this natriuretic peptide can signal in a tissue-specific manner through a receptor other than GC-A.

本文言語英語
ページ(範囲)3807-3813
ページ数7
ジャーナルEndocrinology
141
10
DOI
出版ステータス出版済み - 2000
外部発表はい

!!!All Science Journal Classification (ASJC) codes

  • 内分泌学

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