Inhibition of lung surfactant secretion by KN-62, a specific inhibitor of the calcium- and calmodulin-dependent protein kinase II

Abstract

A role of Ca2+- and calmodulin-dependent protein kinase II (CaMK II in lung surfactant secretion was evaluated using KN-62, a specific inhibitor of CaMK II. KN-62 caused a dose-dependent inhibition of Ca2+ iononphore A23187-stimulated phosphatidylcholine (PC) secretion from cultured alveolar type II cells. Concentration effecting 50% inhibition was ~ 4 μM. However, KN-62 only slightly influenced PC secretion from type II cells stimulated by phorbol 12-myristate 13-acetate, terbutaline and ATP that are known to increase surfactant secretion via the protein kinase C and protein kinase A pathways. KN-62 also inhibited the activity of CaMK II in type II cells. A 55 kDa protein was detected in type II cells by Western blot analysis using an antibody against the β-subunit of CaMK II. The results suggest that CaMK II participates in A23187-stimulated lung surfactant secretion.