title: Ontogeny of atrial natriuretic peptide and its receptor in the lung: effects on perinatal surfactant release.
abstract: During the transition at birth to air breathing, regulation of surfactant release from alveolar type II (ATII) cells is critical. Atrial natriuretic peptide (ANP) stimulates natriuretic peptide receptor-A (NPR-A) and increases intracellular cGMP. We examined the changes in ANP and NPR-A in respiratory epithelium during the perinatal period using immunohistochemistry and studied the effect of ANP on surfactant release from ATII cells isolated from fetal and newborn lambs. NPR-A mRNA was detected in the fetal lung by Northern Blot and RT-PCR. At 100 d gestation (term 145 d), ANP staining was absent and NPR-A staining was weak in cuboidal epithelial cells. ANP and NPR-A staining was prominent in ATII cells at 136 d gestation and was undetectable postnatally. ANP stimulated (maximal effect at 10(-10)M) surfactant release from both late gestation fetal and neonatal ATII cells. Protein kinase G inhibition significantly blocked this release. We conclude that ANP stimulates surfactant release in isolated perinatal ATII cells by a cGMP-dependent mechanism. ANP and NPR-A expression in ATII cells is greatest in late gestation and declines sharply postnatally. We speculate that increased activity of the ANP/NPR-A pathway in late gestation may prime the surfactant system, preparing the lung for air breathing.
authors.affiliation: Department of Pathology and Anatomical Sciences, State University of New York at Buffalo School of Medicine and Biomedical Sciences, Buffalo, New York 14214, USA.
authors.forename: Christopher A
authors.initials: CA
authors.lastname: D'Angelis
authors.forename: Bruce A
authors.initials: BA
authors.lastname: Holm
authors.forename: Satyan
authors.initials: S
authors.lastname: Lakshminrusimha
authors.forename: Peter A
authors.initials: PA
authors.lastname: Nickerson
authors.forename: Daniel D
authors.initials: DD
authors.lastname: Swartz
authors.forename: June
authors.initials: J
authors.lastname: Sokolowski
authors.forename: Lori C
authors.initials: LC
authors.lastname: Nielsen
authors.forename: Rita M
authors.initials: RM
authors.lastname: Ryan
mesh_terms: D000818:Animals; D000831:Animals, Newborn; D009320:Atrial Natriuretic Factor / Q000378:metabolism*; D015152:Blotting, Northern; D002478:Cells, Cultured; D006152:Cyclic GMP / Q000031:analogs & derivatives / Q000494:pharmacology; D017869:Cyclic GMP-Dependent Protein Kinases / Q000037:antagonists & inhibitors / Q000378:metabolism; D005865:Gestational Age; D006162:Guanylate Cyclase / Q000235:genetics / Q000378:metabolism*; D007150:Immunohistochemistry; D008168:Lung / Q000187:drug effects / Q000196:embryology / Q000201:enzymology / Q000254:growth & development / Q000378:metabolism*; D010713:Phosphatidylcholines / Q000378:metabolism; D047428:Protein Kinase Inhibitors / Q000494:pharmacology; D011663:Pulmonary Surfactants / Q000378:metabolism*; D012333:RNA, Messenger / Q000378:metabolism; D017461:Receptors, Atrial Natriuretic Factor / Q000235:genetics / Q000378:metabolism*; D020545:Respiratory Mucosa / Q000187:drug effects / Q000196:embryology / Q000201:enzymology / Q000254:growth & development / Q000378:metabolism*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D012756:Sheep; D015398:Signal Transduction / Q000187:drug effects; D013873:Thionucleotides / Q000494:pharmacology; D013997:Time Factors
chemical_list: D010713:Phosphatidylcholines; D047428:Protein Kinase Inhibitors; D011663:Pulmonary Surfactants; D012333:RNA, Messenger; D013873:Thionucleotides; C098740:8-bromo-beta-phenyl-1,N(2)-ethenoguanosine 3',5'-cyclic monophosphorothioate; D009320:Atrial Natriuretic Factor; D017869:Cyclic GMP-Dependent Protein Kinases; D006162:Guanylate Cyclase; D017461:Receptors, Atrial Natriuretic Factor; C091715:atrial natriuretic factor receptor A; D006152:Cyclic GMP