Natriuretic peptide C receptor in the developing sheep lung: Role in perinatal transition

Bobby Mathew, Christopher A. D'angelis, Satyanarayana Lakshminrusimha, Peter A. Nickerson, June J. Sokolowski, Vasantha H.S. Kumar, Huamei Wang, Karen A. Wynn, Bruce A. Holm, Rita M. Ryan

Research output: Contribution to journalArticle

1 Scopus citations

Abstract

BackgroundAt birth, the release of surfactant from alveolar type II cells (ATIIs) is stimulated by increased activity of the beta-adrenergic/adenylyl cyclase/cyclic 3′-5′ adenosine monophosphate-signaling cascade. Atrial natriuretic peptide (ANP) stimulates surfactant secretion through natriuretic peptide receptor A (NPR-A). ANP inhibits adenylyl cyclase activity through its binding to NPR-C. We wished to further understand the role of the NPR-C in perinatal transition.MethodsWe studied ATII expression of NPR-C in fetal and newborn sheep using immunohistochemistry, and surfactant secretion in isolated ATIIs by measuring 3 [H] choline release into the media.ResultsANP induced surfactant secretion, and, at higher doses, it inhibits the stimulatory effect of the secretagogue terbutaline. ATII NPR-C expression decreased significantly after birth. Premature delivery also markedly decreased ANP and NPR-C in ATIIs. Co-incubation of terbutaline (10 -4 M) with ANP (10 -6 M) significantly decreased 3 [H] choline release from isolated newborn ATII cells when compared with terbutaline alone; this inhibitory effect was mimicked by the specific NPR-C agonist, C-ANP (10 -10 M).ConclusionANP may act as an important epithelial-derived inhibitor of surfactant release in the fetal lung, and downregulation of ANP and NPR-C following birth may sensitize ATII cells to the effects of circulating catecholamines, thus facilitating surfactant secretion.

Original languageEnglish (US)
Pages (from-to)349-355
Number of pages7
JournalPediatric Research
Volume82
Issue number2
DOIs
StatePublished - Aug 1 2017
Externally publishedYes

ASJC Scopus subject areas

  • Pediatrics, Perinatology, and Child Health

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    Mathew, B., D'angelis, C. A., Lakshminrusimha, S., Nickerson, P. A., Sokolowski, J. J., Kumar, V. H. S., Wang, H., Wynn, K. A., Holm, B. A., & Ryan, R. M. (2017). Natriuretic peptide C receptor in the developing sheep lung: Role in perinatal transition. Pediatric Research, 82(2), 349-355. https://doi.org/10.1038/pr.2017.40