title: Natriuretic peptide C receptor in the developing sheep lung: role in perinatal transition.
abstract: Background: At 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. Methods: We studied ATII expression of NPR-C in fetal and newborn sheep using immunohistochemistry, and surfactant secretion in isolated ATIIs by measuring3[H] choline release into the media. Results: ANP 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 (10-4M) with ANP (10-6M) significantly decreased3[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 (10-10M). Conclusion: ANP 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.
authors.affiliation: Department of Pediatrics, State University of New York at Buffalo School of Medicine and Biomedical Sciences, Buffalo, New York.
authors.forename: Bobby
authors.initials: B
authors.lastname: Mathew
authors.affiliation: Department of Pediatrics, State University of New York at Buffalo School of Medicine and Biomedical Sciences, Buffalo, New York.
authors.forename: Christopher A
authors.initials: CA
authors.lastname: D'Angelis
authors.affiliation: Department of Pediatrics, State University of New York at Buffalo School of Medicine and Biomedical Sciences, Buffalo, New York.
authors.forename: Satyan
authors.initials: S
authors.lastname: Lakshminrusimha
authors.affiliation: Department of Pathology, State University of New York at Buffalo School of Medicine and Biomedical Sciences, Buffalo, New York, Posthumously.
authors.forename: Peter A
authors.initials: PA
authors.lastname: Nickerson
authors.affiliation: Department of Pediatrics, State University of New York at Buffalo School of Medicine and Biomedical Sciences, Buffalo, New York.
authors.forename: June J
authors.initials: JJ
authors.lastname: Sokolowski
authors.affiliation: Department of Pediatrics, State University of New York at Buffalo School of Medicine and Biomedical Sciences, Buffalo, New York.
authors.forename: Vasantha H S
authors.initials: VHS
authors.lastname: Kumar
authors.affiliation: Department of Pediatrics, State University of New York at Buffalo School of Medicine and Biomedical Sciences, Buffalo, New York.
authors.forename: Huamei
authors.initials: H
authors.lastname: Wang
authors.affiliation: Department of Pediatrics, State University of New York at Buffalo School of Medicine and Biomedical Sciences, Buffalo, New York.
authors.forename: Karen A
authors.initials: KA
authors.lastname: Wynn
authors.affiliation: Department of Pharmacology, State University of New York at Buffalo School of Medicine and Biomedical Sciences, Buffalo, New York, Posthumously.
authors.forename: Bruce A
authors.initials: BA
authors.lastname: Holm
authors.affiliation: Department of Pediatrics, Medical University of South Carolina, Charleston, South Carolina.
authors.forename: Rita M
authors.initials: RM
authors.lastname: Ryan
mesh_terms: D000818:Animals; D000831:Animals, Newborn; D007150:Immunohistochemistry; D008168:Lung / Q000378:metabolism*; D020098:Natriuretic Peptide, C-Type / Q000378:metabolism*; D037342:Pertussis Toxin / Q000494:pharmacology; D011663:Pulmonary Surfactants / Q000378:metabolism; D012756:Sheep / Q000196:embryology*; D013726:Terbutaline / Q000494:pharmacology
chemical_list: D011663:Pulmonary Surfactants; D020098:Natriuretic Peptide, C-Type; D037342:Pertussis Toxin; D013726:Terbutaline