Lipoprotein-stimulated surfactant secretion in alveolar type II cells: mediation by heterotrimeric G proteins.
Low- and high-density lipoproteins (LDL and HDL, respectively) stimulate alveolar type II cells to secrete surfactant. Increases in phosphoinositide hydrolysis, cytosolic Ca2+, and membrane-associated protein kinase C activity precede LDL- and HDL-stimulated secretion. We report three lines of evidence supporting the hypothesis that Gi mediates LDL- and HDL-stimulated surfactant secretion and signal transduction in type II cells. First, pertussis toxin (PTX) inhibited secretion stimulated by the apolipoprotein ligands for either the LDL receptor or the HDL binding protein. Second, PTX inhibited protein kinase C activity in cell membranes stimulated by LDL or HDL. Third, treatment of cell membranes with LDL or HDL inhibited PTX-catalyzed labeling of substrates corresponding in molecular mass to Gi alpha. These observations suggest that receptor-mediated activation of Gi is required for LDL- and HDL-stimulated secretion and that LDL and HDL activate Gi. These studies in type II cells are the first to support the hypothesis that Gi mediates the effects of LDL or HDL on important phenotype-specific functions of differentiated cells.
Pian
M S
MS
Department of Pediatrics, University of California, San Francisco 94143-0130, USA.
Dobbs
L G
LG
D000818:Animals; D016632:Apolipoprotein A-I / Q000494:pharmacology; D001057:Apolipoproteins E / Q000494:pharmacology; D002352:Carrier Proteins; D002478:Cells, Cultured; D019204:GTP-Binding Proteins / Q000096:biosynthesis / Q000502:physiology*; D008075:Lipoproteins, HDL / Q000494:pharmacology*; D008077:Lipoproteins, LDL / Q000494:pharmacology*; D046911:Macromolecular Substances; D008297:Male; D037342:Pertussis Toxin; D010713:Phosphatidylcholines / Q000378:metabolism; D011493:Protein Kinase C / Q000378:metabolism; D011650:Pulmonary Alveoli / Q000187:drug effects / Q000378:metabolism / Q000502:physiology*; D011663:Pulmonary Surfactants / Q000378:metabolism*; D016601:RNA-Binding Proteins; D051381:Rats; D017207:Rats, Sprague-Dawley; D011973:Receptors, LDL / Q000187:drug effects / Q000502:physiology*; D018110:Receptors, Lipoprotein / Q000187:drug effects / Q000502:physiology*; D010566:Virulence Factors, Bordetella / Q000494:pharmacology
D016632:Apolipoprotein A-I; D001057:Apolipoproteins E; D002352:Carrier Proteins; D008075:Lipoproteins, HDL; D008077:Lipoproteins, LDL; D046911:Macromolecular Substances; D010713:Phosphatidylcholines; D011663:Pulmonary Surfactants; D016601:RNA-Binding Proteins; D011973:Receptors, LDL; D018110:Receptors, Lipoprotein; D010566:Virulence Factors, Bordetella; C031616:high density lipoprotein receptors; C075197:high density lipoprotein binding protein; D037342:Pertussis Toxin; D011493:Protein Kinase C; D019204:GTP-Binding Proteins