Glucagon-like peptide-1(7-36) amide stimulates surfactant secretion in human type II pneumocytes.
To determine the influence of glucagon-like peptides on the secretion of human pulmonary surfactant, we used human type II pneumocytes. In these cells, GLP-1(7-36) amide and exendin-4 stimulated phosphatidylcholine secretion (PC) and cAMP formation in a concentration-dependent manner; these effects were reversed by exendin(9-39). No changes were observed with other related peptides. The mechanism by which GLP-1(7-36) amide exerts its stimulatory effect was investigated with various agents that are well known to be stimulators or inhibitors of PC secretion. Thus, 8-bromo-cAMP increased and both Rp-cAMPS and H-89, the latter an inhibitor of protein kinase A (PKA), reduced pulmonary surfactant secretion in type II pneumocytes. Also, GLP-1(7-36) amide and TPA exerted additive effects in stimulating PC secretion, and Calph C, a potent inhibitor of protein kinase C (PKC), blocked most of the effect of GLP-1(7-36) amide. By contrast, both the calcium ionophore A23187 and GLP-1(7-36) amide had additive effects in increasing PC secretion, and the specific inhibitor of Ca(2+)-calmodulin-dependent protein kinase (Ca-CM-PK), KN-62, inhibited the effect of A23187 but did not alter the stimulatory action of GLP-1(7-36) amide. Our findings suggest that both PKA and PKC are involved in the stimulatory effects of GLP-1(7-36) amide on PC secretion, whereas this peptide has no effect on PC secretion through a Ca-CM-PK mechanism.
Vara
E
E
Department of Biochemistry and Molecular Biology, Faculty of Medicine, Complutense University, Madrid, Spain.
Arias-Díaz
J
J
Garcia
C
C
Balibrea
J L
JL
Blázquez
E
E
D000328:Adult; D002478:Cells, Cultured; D004305:Dose-Response Relationship, Drug; D005260:Female; D005934:Glucagon; D052216:Glucagon-Like Peptide 1; D004763:Glucagon-Like Peptides; D006801:Humans; D008168:Lung / Q000166:cytology / Q000378:metabolism*; D008297:Male; D008875:Middle Aged; D010446:Peptide Fragments / Q000378:metabolism* / Q000494:pharmacology; D010713:Phosphatidylcholines / Q000032:analysis; D011663:Pulmonary Surfactants / Q000187:drug effects / Q000378:metabolism*; D012016:Reference Values; D012680:Sensitivity and Specificity
D010446:Peptide Fragments; D010713:Phosphatidylcholines; D011663:Pulmonary Surfactants; C055453:glucagon-like peptide 1 (7-36)amide; D004763:Glucagon-Like Peptides; D052216:Glucagon-Like Peptide 1; D005934:Glucagon