REGULATION OF LUNG SURFACTANT SECRETION BY PHOSPHOLIPASE A(2)

Authors
Citation
L. Liu, REGULATION OF LUNG SURFACTANT SECRETION BY PHOSPHOLIPASE A(2), Journal of cellular biochemistry, 72(1), 1999, pp. 103-110
Citations number
43
Language
INGLESE
art.tipo
Article
Categorie Soggetti
Biology,"Cell Biology
ISSN journal
0730-2312
Volume
72
Issue
1
Year of publication
1999
Pages
103 - 110
Database
ISI
SICI code
0730-2312(1999)72:1<103:ROLSSB>2.0.ZU;2-3
Abstract
Arachidonic acid has been shown to stimulate lung surfactant secretion from alveolar epithelial type II cells. To identify the (phospho)lipa ses responsible for generating arachidonic acid during lung surfactant secretion, the effects of various (phospho)lipase inhibitors on phosp hatidylcholine (PC) secretion from rat alveolar type II cells were inv estigated. N-(p-amylcinnamoyl)anthranilic acid (ACA), a general inhibi tor of phospholipase A(2) (PLA(2)), inhibited ATP-stimulated PC secret ion in a dose-dependent manner. ACA also blocked PC secretion from typ e II cells stimulated by other secretagogues including phorbol 12-myri state 13-acetate, Ca2+ ionophore A23187 and terbutaline, indicating th at PLA(2) acts at a late step distal to the generation of second messe ngers. To determine which PLA(2) isoform(s) is involved in lung surfac tant secretion, selective inhibitors to different types of PLA(2) were used to inhibit PLA(2) activity in type II cells. The cytosolic PLA(2 ) (cPLA(2)) inhibitor, arachidonyl trifluoromethyl ketone, was found t o inhibit ATP-stimulated PC secretion, whereas the secretory PLA(2) in hibitors, oleoyloxyethylphosphocholine, aristolochic acid, or p-bromop henacyl bromide, and the Ca2+-independent PLA(2) inhibitors, palmitoyl trifluoromethyl ketone, or haloenol lactone suicide substrate, had no effect. In addition to PLA(2), arachidonic acid is released from diac ylglycerol (DAG) by DAG and monoacylglycerol lipases. The DAG lipase i nhibitor, RHC-80267 also blocked ATP-stimulated PC secretion. The resu lts suggest that both pathways for generating arachidonic acid via cPL A(2) and DAG lipase may participate in lung surfactant secretion. J. C ell. Biochem. 72:103-110, 1999. (C) 1999 Wiley-Liss, Inc.