Glucagon-like peptide-1-(7-36)amide increases pulmonary surfactant secretion through a cyclic adenosine 3',5'-monophosphate-dependent protein kinase mechanism in rat type II pneumocytes.
Glucagon-like peptide-1 (GLP-1) receptor messenger RNA has been identified in cells considered type II pneumocytes that are involved in the synthesis and secretion of the pulmonary surfactant. In an attempt to open new insights into the control of surfactant secretion, we studied the effects of glucagon-related peptides in this process. Accordingly, type II pneumocytes were isolated from Wistar rat lungs and cultured overnight with [methyl-14C]choline, and then the basal and stimulated secretions of [14C]phosphatidylcholine were measured. GLP-1(7-36)amide stimulated phosphatidylcholine secretion in a concentration-dependent manner in the 1-100 nM range; the concentration of the peptide that produced a half-maximal response was 10 nM. Exendin-4 induced similar effects. No changes were observed when GLP-1-(1-37), GLP-2, or exendin-(9-39) was added to the medium. However, the latter reversed the stimulatory effects of GLP-1-(7-36)amide and exendin-4. A study of the mechanism through which GLP-1-(7-36)amide exerts its stimulatory effect was carried out using different agents that are well known stimulants of phosphatidylcholine secretion. GLP-1-(7-36)amide did not produce any change in the stimulatory effect observed with terbutaline or 8-bromo-cAMP, suggesting the involvement of a cAMP-dependent protein kinase in the stimulatory effect of this peptide on phosphatidylcholine secretion. It was further supported by the use of inhibitors of protein kinases and by the stimulation of cAMP production in type II pneumocytes incubated with either GLP-1-(7-36)amide or exendin-4.
Benito
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Department of Biochemistry and Molecular Biology I, Faculty of Chemistry, Universidad Complutense, Madrid, Spain.
Blazquez
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Bosch
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MA
D000318:Adrenergic beta-Agonists / Q000494:pharmacology; D000818:Animals; D000001:Calcimycin / Q000494:pharmacology; D000252:Calcium-Transporting ATPases / Q000037:antagonists & inhibitors; D002478:Cells, Cultured; D054746:Cyclic AMP-Dependent Protein Kinase Type II; D017868:Cyclic AMP-Dependent Protein Kinases / Q000378:metabolism*; D004789:Enzyme Activation / Q000187:drug effects; D004791:Enzyme Inhibitors / Q000494:pharmacology; D005934:Glucagon; D052216:Glucagon-Like Peptide 1; D004763:Glucagon-Like Peptides; D007700:Kinetics; D008168:Lung / Q000187:drug effects* / Q000378:metabolism*; D008297:Male; D010446:Peptide Fragments / Q000494:pharmacology*; D010713:Phosphatidylcholines / Q000378:metabolism; D011663:Pulmonary Surfactants / Q000378:metabolism*; D051381:Rats; D017208:Rats, Wistar; D013726:Terbutaline / Q000494:pharmacology; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology; D019284:Thapsigargin / Q000494:pharmacology
D000318:Adrenergic beta-Agonists; D004791:Enzyme Inhibitors; D010446:Peptide Fragments; D010713:Phosphatidylcholines; D011663:Pulmonary Surfactants; C055453:glucagon-like peptide 1 (7-36)amide; D000001:Calcimycin; D004763:Glucagon-Like Peptides; D019284:Thapsigargin; D052216:Glucagon-Like Peptide 1; D005934:Glucagon; D054746:Cyclic AMP-Dependent Protein Kinase Type II; D017868:Cyclic AMP-Dependent Protein Kinases; D000252:Calcium-Transporting ATPases; D013726:Terbutaline; D013755:Tetradecanoylphorbol Acetate