LIPOPROTEIN-STIMULATED SURFACTANT SECRETION IN ALVEOLAR TYPE-II CELLS- MEDIATION BY HETEROTRIMERIC G-PROTEINS

Low- and high-density lipoproteins (LDL and HDL, respectively) stimula te alveolar type II cells to secrete surfactant. Increases in phosphoi nositide hydrolysis, cytosolic Ca2+, and membrane-associated protein k inase C activity precede LDL-and HDL-stimulated secretion. We report t hree lines of evidence supporting the hypothesis that Gi mediates LDL- and HDL-stimulated surfactant secretion and signal transduction in typ e II cells. First, pertussis toxin (PTX) inhibited secretion stimulate d by the apolipoprotein Ligands for either the LDL receptor or the HDL binding protein. Second, PTX inhibited protein kinase C activity in c ell membranes stimulated by LDL or HDL. Third, treatment of cell membr anes with LDL or HDL inhibited PTX-catalyzed labeling of substrates co rresponding in molecular mass to G(i) alpha. These observations sugges t that receptor-mediated activation of G(i) is required for LDL-and HD L-stimulated secretion and that LDL and HDL activate G(i). These studi es in type II cells are the first to support the hypothesis that G(i) mediates the effects of LDL or HDL on important phenotype-specific fun ctions of differentiated cells.