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 identi fied 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-C-14] choline, and then the basal and stimulat ed secretions of [C-14]phosphatidylcholine were measured. GLP-1(7-36)a mide stimulated phosphatidylcholine secretion in a concentration-depen dent manner in the 1-100 nM range; the concentration of the peptide th at produced a half-maximal response was 10 nM. Exendin-4 induced simil ar effects. No changes were observed when GLP-1-(1-37), GLP-2, or exen din-(9-39) was added to the medium. However, the latter reversed the s timulatory 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 effec t was carried out using different agents that are well known stimulant s of phosphatidylcholine secretion. GLP-1-(7-36)amide did not produce any change in the stimulatory effect observed with terbutaline or 8-br omo-cAMP, suggesting the involvement of a CAMP-dependent protein kinas e in the stimulatory effect of this peptide on phosphatidylcholine sec retion. It was further supported by the use of inhibitors of protein k inases and by the stimulation of CAMP production in type TT pneumocyte s incubated with either GLP-1-(7-36)amide or exendin-4.