PROTEIN-KINASE-C IN ATP REGULATION OF LUNG SURFACTANT SECRETION IN TYPE-II CELLS

Previous studies provided indirect evidence for a role for protein kin ase C (PKC) in ATP stimulation of surfactant secretion. The present st udy demonstrates that ATP increases PKC activity in the membrane fract ion and decreases PKC activity in the cytosol fraction of alveolar typ e II cells, indicating translocation of PKC to the membranes. The kine tics of ATP concentration dependence of increases in phosphatidylcholi ne secretion and diacylglycerol content were similar, suggesting a dir ect correlation between these two parameters. ATP also increased membr ane PKC activity in a concentration-dependent manner. Almost one-half of the PKC activity in the cytosol and membrane fractions was Ca2+ ind ependent. The ATP-induced increase was greater in membrane-associated Ca2+-dependent enzyme (233%) than in Ca2+-independent enzyme (121%). D esensitization of PKC by exposure of cells to phorbol esters decreased PKC activity in the membrane and cytosol fractions. In cells pretreat ed for 3 h with phorbol esters, PKC activity was near minimum, and ATP -stimulated secretion was lowest (<40% of that observed in untreated c ells). These results indicate that a major part of ATP-stimulated surf actant secretion in type II cells is mediated via activation of PKC.