Inhibition of lung surfactant secretion by KN-62, a specific inhibitor of the calcium- and calmodulin-dependent protein kinase II.
A role of Ca(2+)- 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 approximately 4 microM. 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 beta-subunit of CaMK II. The results suggest that CaMK II participates in A23187-stimulated lung surfactant secretion.
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Department of Physiology, East Carolina University School of Medicine, Greenville, NC 27858, USA.
D019307:1-(5-Isoquinolinesulfonyl)-2-Methylpiperazine / Q000031:analogs & derivatives* / Q000494:pharmacology; D000255:Adenosine Triphosphate / Q000494:pharmacology; D000818:Animals; D000001:Calcimycin / Q000494:pharmacology; D054732:Calcium-Calmodulin-Dependent Protein Kinase Type 2; D017871:Calcium-Calmodulin-Dependent Protein Kinases / Q000037:antagonists & inhibitors / Q000378:metabolism*; D002478:Cells, Cultured; D004305:Dose-Response Relationship, Drug; D004791:Enzyme Inhibitors / Q000494:pharmacology; D007476:Ionophores / Q000494:pharmacology; D008297:Male; D010713:Phosphatidylcholines / Q000378:metabolism*; D011650:Pulmonary Alveoli / Q000166:cytology / Q000201:enzymology / Q000378:metabolism*; D051381:Rats; D017207:Rats, Sprague-Dawley; D013726:Terbutaline / Q000494:pharmacology; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology
D004791:Enzyme Inhibitors; D007476:Ionophores; D010713:Phosphatidylcholines; D000001:Calcimycin; C063302:KN 62; D019307:1-(5-Isoquinolinesulfonyl)-2-Methylpiperazine; D000255:Adenosine Triphosphate; D054732:Calcium-Calmodulin-Dependent Protein Kinase Type 2; D017871:Calcium-Calmodulin-Dependent Protein Kinases; D013726:Terbutaline; D013755:Tetradecanoylphorbol Acetate