Bombesin-like peptides and receptors in normal fetal baboon lung: roles in lung growth and maturation.
Previously, we have shown that bombesin-like peptide (BLP) promotes fetal lung development in rodents and humans but mediates postnatal lung injury in hyperoxic baboons. The present study analyzed the normal ontogeny of BLP and BLP receptors as well as the effects of BLP on cultured normal fetal baboon lungs. Transcripts encoding gastrin-releasing peptide (GRP), a pulmonary BLP, were detectable on gestational day 60 (ED60), peaked on approximately ED90, and then declined before term (ED180). Numbers of BLP-immunopositive neuroendocrine cells peaked from ED80 to ED125 and declined by ED160, preceding GRP-receptor mRNAs detected from ED125 until birth. BLP (0.1-10 nM) stimulated type II cell differentiation in organ cultures as assessed by [(3)H]choline incorporation into surfactant phospholipids, electron microscopy, and increased surfactant protein (SP) A- and/or SP-C-immunopositive cells and SP-A mRNA. BLP also induced neuroendocrine differentiation on ED60. Cell proliferation was induced by GRP, peaking on ED90. Similarly, blocking BLP degradation stimulated lung growth and maturation, which was completely reversed by a BLP-specific antagonist. The dissociation between GRP and GRP-receptor gene expression during ontogeny suggests that novel BLP receptors and/or peptides might be implicated in these responses.
Emanuel
R L
RL
Department of Medicine, Children's Hospital and Harvard Medical School, Boston, Massachusetts 02115, USA.
Torday
J S
JS
Mu
Q
Q
Asokananthan
N
N
Sikorski
K A
KA
Sunday
M E
ME
D000595:Amino Acid Sequence; D029845:Amphibian Proteins; D000818:Animals; D000893:Anti-Inflammatory Agents / Q000494:pharmacology; D023181:Antimicrobial Cationic Peptides; D002454:Cell Differentiation / Q000187:drug effects; D002455:Cell Division / Q000187:drug effects; D002794:Choline / Q000378:metabolism / Q000494:pharmacology; D017931:DNA Primers; D003907:Dexamethasone / Q000494:pharmacology; D004151:Dipeptides / Q000494:pharmacology; D004815:Epidermal Growth Factor / Q000494:pharmacology; D005333:Fetus / Q000166:cytology; D019886:Gastrin-Releasing Peptide / Q000032:analysis / Q000235:genetics*; D018507:Gene Expression Regulation, Developmental; D017403:In Situ Hybridization; D008168:Lung / Q000737:chemistry* / Q000166:cytology / Q000196:embryology*; D008969:Molecular Sequence Data; D015260:Neprilysin / Q000494:pharmacology; D009842:Oligopeptides / Q000494:pharmacology; D009924:Organ Culture Techniques; D010215:Papio; D010446:Peptide Fragments / Q000032:analysis / Q000235:genetics / Q000494:pharmacology; D010455:Peptides / Q000032:analysis / Q000235:genetics* / Q000494:pharmacology; D011480:Protease Inhibitors / Q000494:pharmacology; D011510:Proteolipids / Q000032:analysis / Q000235:genetics; D037662:Pulmonary Surfactant-Associated Protein A; D037661:Pulmonary Surfactant-Associated Proteins; D011663:Pulmonary Surfactants / Q000032:analysis / Q000235:genetics; D011761:Pyrrolidonecarboxylic Acid / Q000031:analogs & derivatives; D012333:RNA, Messenger / Q000032:analysis; D018004:Receptors, Bombesin / Q000032:analysis / Q000235:genetics*; D014316:Tritium
D029845:Amphibian Proteins; D000893:Anti-Inflammatory Agents; D023181:Antimicrobial Cationic Peptides; D017931:DNA Primers; D004151:Dipeptides; D009842:Oligopeptides; D010446:Peptide Fragments; D010455:Peptides; D011480:Protease Inhibitors; D011510:Proteolipids; D037662:Pulmonary Surfactant-Associated Protein A; D037661:Pulmonary Surfactant-Associated Proteins; D011663:Pulmonary Surfactants; D012333:RNA, Messenger; D018004:Receptors, Bombesin; D014316:Tritium; D004815:Epidermal Growth Factor; D003907:Dexamethasone; D019886:Gastrin-Releasing Peptide; C041922:gastrin releasing peptide (14-27); C062344:SCH 32615; C043155:phyllolitorin; D015260:Neprilysin; D002794:Choline; D011761:Pyrrolidonecarboxylic Acid