Ontogeny of atrial natriuretic peptide and its receptor in the lung: effects on perinatal surfactant release.
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.
D'Angelis
Christopher A
CA
Department of Pathology and Anatomical Sciences, State University of New York at Buffalo School of Medicine and Biomedical Sciences, Buffalo, New York 14214, USA.
Holm
Bruce A
BA
Lakshminrusimha
Satyan
S
Nickerson
Peter A
PA
Swartz
Daniel D
DD
Sokolowski
June
J
Nielsen
Lori C
LC
Ryan
Rita M
RM
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
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