Atrial natriuretic peptide modulates alveolar type 2 cell adenylyl and guanylyl cyclases and inhibits surfactant secretion

• Published in: Biochimica et biophysica acta 1998-05, Vol.1403 (1), p.115-125
• Main Authors: Panchenko, Mikhail P, Joyce-Brady, Martin, Starikova, Marina G, Oakes, Sean M, Adachi, Roberto, Brody, Jerome S, Dickey, Burton F
• Format: Article
• Language: English
• Subjects: Adenylate Cyclase Toxin; Adenylyl cyclase; Adenylyl Cyclases - drug effects; Adenylyl Cyclases - metabolism; Animals; Atrial Natriuretic Factor - administration & dosage; Atrial Natriuretic Factor - pharmacology; Atrial natriuretic peptide; Bronchodilator Agents - pharmacology; Cell Membrane - drug effects; Cell Membrane - enzymology; Cyclic AMP - metabolism; Cyclic GMP - metabolism; Dose-Response Relationship, Drug; Epithelial Cells - cytology; Epithelial Cells - drug effects; Epithelial Cells - enzymology; GTP-Binding Proteins - drug effects; GTP-Binding Proteins - metabolism; Guanylate Cyclase - drug effects; Guanylate Cyclase - metabolism; Guanylyl cyclase; Isoproterenol - pharmacology; Ligands; Lung epithelial type 2 cell; Pertussis Toxin; Phosphatidylcholines - metabolism; Pulmonary Alveoli - cytology; Pulmonary Alveoli - drug effects; Pulmonary Alveoli - enzymology; Rats; Secretion; Surface-Active Agents - metabolism; Surfactant; Virulence Factors, Bordetella - pharmacology
• ISSN: 0167-4889; 0006-3002; 1879-2596
• DOI: 10.1016/S0167-4889(98)00023-8

Alveolar epithelial type 2 (T2) cells isolated from the lungs of adult rats responded to exogenous atrial natriuretic peptide (ANP) by two signalling mechanisms. First, ANP induced a dose-dependent reduction of ligand-stimulated adenylyl cyclase activity and cAMP accumulation. This effect was inhibited by the addition of GDP βS or by pretreatment with pertussis toxin (PT), consistent with mediation by a Gi protein(s). PT-catalyzed [ 32 P ]ADP-ribosylation, immunoblots with specific antisera, and Northern blot analysis demonstrated that T2 cells contain the G-proteins Gi 2 and Gi 3 which could transduce this signal. ANP also promoted PT-insensitive, dose-dependent accumulation of cGMP, consistent with activation of a receptor guanylyl cyclase. Isoproterenol-stimulated phosphatidylcholine secretion was markedly attenuated by ANP, and this effect was inhibited by PT pretreatment, consistent with mediation by a Gi protein(s). These data indicate that in addition to the lung being a major clearance organ for circulating ANP, lung parenchymal cells are targets of ANP action.