Fetal alveolar epithelial cells contain [D-Ala(2)]-deltorphin I-like immunoreactivity: delta- and mu-opiate receptors mediate opposite effects in developing lung

• Published in: American journal of respiratory cell and molecular biology Vol. 25; no. 4; pp. 447 - 456
• Main Authors: Sunday, M E, Haley, K J, Emanuel, R L, Torday, J S, Asokananthan, N, Sikorski, K A, Tooyama, I, Kimura, H, Renda, T, Erspamer, V
• Format: Journal Article
• Language: English
• Published: United States 01-10-2001
• Subjects: Animals; Choline - metabolism; Female; Gene Expression Regulation, Developmental; Lung - drug effects; Lung - embryology; Mice; Oligopeptides - immunology; Oligopeptides - pharmacology; Organ Culture Techniques; Peptides - immunology; Pregnancy; Proliferating Cell Nuclear Antigen - immunology; Pulmonary Alveoli - cytology; Pulmonary Alveoli - embryology; Pulmonary Alveoli - immunology; Pulmonary Surfactants - immunology; Receptors, Opioid - genetics; Respiratory Mucosa - drug effects; Respiratory Mucosa - embryology; Respiratory Mucosa - immunology; Thymidine - pharmacokinetics
• ISSN: 1044-1549; 1535-4989
• DOI: 10.1165/ajrcmb.25.4.4072

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.