Am. J. Respir. Crit. Care Med., Volume 163, Number 4, March 2001, 840-846

Glucagon-like Peptide-1(7-36) Amide Stimulates Surfactant Secretion in Human Type II Pneumocytes

ELENA VARA, JAVIER ARIAS-DÍAZ, CRUZ GARCIA, JOSÉ LUIS BALIBREA, and ENRIQUE BLÁZQUEZ

Department of Biochemistry and Molecular Biology, Faculty of Medicine, Complutense University, Madrid, Spain; Department of Surgery, Hospital Clínico San Carlos, Faculty of Medicine, Complutense University, Madrid, Spain; and Clinical Biochemistry Service, Hospital Clínico San Carlos Pabellón 8, Madrid, Spain

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 Ca²⁺-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.

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