Interaction between β-adrenergic signaling and protein kinase C increases cytoplasmic Ca 2+ in alveolar type II cells

Abstract

The interaction between β-adrenergic signaling and the activation of protein kinase C in alveolar type II cell plays an important role in the regulation of surfactant secretion because the combined application of β-adrenergic agonist with protein kinase C activator to the cells stimulates the secretion synergistically. However, the mechanisms underlying the interaction are not clear. In the present study, we examined the combined effect of terbutaline with phorbol 12-myristate 13-acetate (PMA) on cytoplasmic free Ca 2+ concentration ([Ca 2+] i) in rat alveolar type II cells. The combined application of terbutaline with PMA to the cells rapidly increased [Ca 2+] i, although neither of them affected it by itself. Similar increases of [Ca 2+] i were observed in other combinations, such as terbutaline with 1-oleoyl-2-acetyl-sn-glycerol, and forskolin with PMA. Either the removal of extracellular Ca 2+ or the addition of Co 2+ remarkably suppressed the increase of [Ca 2+] i induced by the combination of terbutaline with PMA. In addition, Co 2+ inhibited the phosphatidylcholine secretion induced by the combination of terbutaline and PMA. These results suggested that the [Ca 2+] i increased as a result of the interaction between formation of cyclic AMP and activation of protein kinase C in alveolar type II cells, and that the increase in [Ca 2+] i was mediated by the Ca 2+ influx through the plasma membrane. This mechanism to modulate [Ca 2+] i may play a role in the regulation of surfactant secretion by alveolar type II cells.