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.
Publication types
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Research Support, N.I.H., Extramural
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Research Support, Non-U.S. Gov't
MeSH terms
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Animals
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Animals, Newborn
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Atrial Natriuretic Factor / metabolism*
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Blotting, Northern
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Cells, Cultured
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Cyclic GMP / analogs & derivatives
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Cyclic GMP / pharmacology
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Cyclic GMP-Dependent Protein Kinases / antagonists & inhibitors
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Cyclic GMP-Dependent Protein Kinases / metabolism
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Gestational Age
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Guanylate Cyclase / genetics
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Guanylate Cyclase / metabolism*
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Immunohistochemistry
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Lung / drug effects
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Lung / embryology
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Lung / enzymology
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Lung / growth & development
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Lung / metabolism*
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Phosphatidylcholines / metabolism
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Protein Kinase Inhibitors / pharmacology
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Pulmonary Surfactants / metabolism*
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RNA, Messenger / metabolism
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Receptors, Atrial Natriuretic Factor / genetics
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Receptors, Atrial Natriuretic Factor / metabolism*
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Respiratory Mucosa / drug effects
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Respiratory Mucosa / embryology
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Respiratory Mucosa / enzymology
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Respiratory Mucosa / growth & development
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Respiratory Mucosa / metabolism*
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Reverse Transcriptase Polymerase Chain Reaction
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Sheep
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Signal Transduction* / drug effects
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Thionucleotides / pharmacology
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Time Factors
Substances
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Phosphatidylcholines
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Protein Kinase Inhibitors
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Pulmonary Surfactants
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RNA, Messenger
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Thionucleotides
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8-bromo-beta-phenyl-1,N(2)-ethenoguanosine 3',5'-cyclic monophosphorothioate
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Atrial Natriuretic Factor
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Cyclic GMP-Dependent Protein Kinases
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Guanylate Cyclase
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Receptors, Atrial Natriuretic Factor
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atrial natriuretic factor receptor A
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Cyclic GMP