Interaction between beta-adrenergic signaling and protein kinase C increases cytoplasmic Ca2+ in alveolar type II cells

The interaction between beta -adrenergic signaling and the activation of pr otein kinase C in alveolar type II cell plays an important role in the regu lation of surfactant secretion because the combined application of beta -ad renergic agonist with protein kinase C activator to the cells stimulates th e secretion synergistically. However, the mechanisms underlying the interac tion are not clear. In the present study, we examined the combined effect o f terbutaline with phorbol 12-myristate 13-acetate (PMA) on cytoplasmic fre e Ca2+ concentration ([Ca2+](i)) in rat alveolar type II cells. The combine d application of terbutaline with PMA to the cells rapidly increased [Ca2+] (i), although neither of them affected it by itself. Similar increases of [ Ca2+](i) were observed in other combinations, such as terbutaline with 1-ol eoyl-2-acetyl-sn-glycerol, and forskolin with PMA. Either the removal of ex tracellular Ca2+ or the addition of Co2+ remarkably suppressed the increase of [Ca2+](i) induced by the combination of terbutaline with PMA. In additi on, Co2+ inhibited the phosphatidylcholine secretion induced by the combina tion of terbutaline and PMA. These results suggested that the [Ca2+](i) inc reased as a result of the interaction between formation of cyclic AMP and a ctivation of protein kinase C in alveolar type II cells, and that the incre ase in [Ca2+](i) was mediated by the Ca2+ influx through the plasma membran e. This mechanism to modulate [Ca2+](i) may play a role in the regulation o f surfactant secretion by alveolar type II cells. (C) 2001 Elsevier Science Inc. All rights reserved.