Fetal alveolar epithelial cells contain [D-Ala(2)]-deltorphin I-like immunoreactivity: delta- and mu-opiate receptors mediate opposite effects in developing lung.
Opiate-like peptides can regulate many cellular functions. We now map [D-Ala(2)]deltorphin I (DADTI)-like immunoreactivity (DADTI-LI) in developing mouse lung and analyze potential functional roles. Most DADTI-LI-positive cells were alveolar cells negative for prosurfactant protein (proSP)-C immunoreactivity. Peak numbers of DADTI-LI-positive cells occurred on embryonic Day 18, decreasing postnatally. To analyze developmental effects of DADTI, e17-18 lung explants were treated with [D-Ala(2)]deltorphin II (DADTII, soluble DADTI analogue, delta-receptor-specific) versus dermorphin (mu-receptor-specific). Type II pneumocyte differentiation, assessed by [(3)H]choline incorporation into saturated phosphatidylcholine and proSP-C immunostaining, was inhibited by DADTII but stimulated by dermorphin. Cell proliferation, measured as [(3)H]-thymidine incorporation and proliferating cell nuclear antigen immunostaining, was stimulated by DADTII and inhibited by dermorphin. All effects were dose-dependent. DADTII-inhibited choline incorporation was reversed by the delta-blocker, naltrindole. Unexpectedly, DADTII-stimulated thymidine incorporation was augmented by naltrindole and reversed by naloxone (mu-blocker). Although dermorphin-stimulated choline incorporation was appropriately blocked by binaltorphimine, dermorphin-inhibited thymidine incorporation was reversed by delta, kappa-, or mu-blockers. The delta- and mu-receptor messenger RNAs occurred pre- and postnatally, whereas kappa-receptor transcripts occurred mainly prenatally. All three receptor proteins were present in epithelial and mesenchymal cells in e18 lung. Thus, DADTI-LI from proSP-C-immunonegative alveolar cells could regulate development via both direct and indirect effects involving multiple opiate receptors.
Sunday
M E
ME
Department of Pathology, Children's Hospital, Enders 909, 300 Longwood Ave., Boston, MA 02115, USA.
Haley
K J
KJ
Emanuel
R L
RL
Torday
J S
JS
Asokananthan
N
N
Sikorski
K A
KA
Tooyama
I
I
Kimura
H
H
Renda
T
T
Erspamer
V
V
D000818:Animals; D002794:Choline / Q000378:metabolism; D005260:Female; D018507:Gene Expression Regulation, Developmental; D036341:Intercellular Signaling Peptides and Proteins; D008168:Lung / Q000187:drug effects / Q000196:embryology; D051379:Mice; D009842:Oligopeptides / Q000276:immunology* / Q000494:pharmacology; D009924:Organ Culture Techniques; D010455:Peptides / Q000276:immunology; D011247:Pregnancy; D018809:Proliferating Cell Nuclear Antigen / Q000276:immunology; D011650:Pulmonary Alveoli / Q000166:cytology / Q000196:embryology* / Q000276:immunology; D037721:Pulmonary Surfactant-Associated Protein C; D011663:Pulmonary Surfactants / Q000276:immunology; D011957:Receptors, Opioid / Q000235:genetics*; D020545:Respiratory Mucosa / Q000187:drug effects / Q000196:embryology* / Q000276:immunology*; D013936:Thymidine / Q000493:pharmacokinetics
D036341:Intercellular Signaling Peptides and Proteins; D009842:Oligopeptides; D010455:Peptides; D018809:Proliferating Cell Nuclear Antigen; D037721:Pulmonary Surfactant-Associated Protein C; D011663:Pulmonary Surfactants; D011957:Receptors, Opioid; C489680:Sftpc protein, mouse; C060209:deltorphin II, Ala(2)-; D002794:Choline; D013936:Thymidine