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
E. Benito et al., 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, Endocrinology, 139(5), 1998, pp. 2363-2368
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.