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Regulation of lung surfactant secretion by phospholipase A 2
Author(s) -
Liu Lin
Publication year - 1999
Publication title -
journal of cellular biochemistry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.028
H-Index - 165
eISSN - 1097-4644
pISSN - 0730-2312
DOI - 10.1002/(sici)1097-4644(19990101)72:1<103::aid-jcb11>3.0.co;2-5
Subject(s) - arachidonic acid , secretion , phospholipase a2 , diacylglycerol lipase , phorbol , chemistry , biochemistry , monoacylglycerol lipase , diacylglycerol kinase , biology , protein kinase c , enzyme , receptor , endocannabinoid system
Arachidonic acid has been shown to stimulate lung surfactant secretion from alveolar epithelial type II cells. To identify the (phospho)lipases responsible for generating arachidonic acid during lung surfactant secretion, the effects of various (phospho)lipase inhibitors on phosphatidylcholine (PC) secretion from rat alveolar type II cells were investigated. N‐(p‐amylcinnamoyl)anthranilic acid (ACA), a general inhibitor of phsopholipase A 2 (PLA 2 ), inhibited ATP‐stimulated PC secretion in a dose‐dependent manner. ACA also blocked PC secretion from type II cells stimulated by other secretagogues including phorbol 12‐myristate 13‐acetate, Ca 2+ ionophore A23187 and terbutaline, indicating that PLA 2 acts at a late step distal to the generation of second messengers. To determine which PLA 2 isoform(s) is involved in lung surfactant 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 to inhibit ATP‐stimulated PC secretion, whereas the secretory PLA 2 inhibitors, oleoyloxyethylphosphocholine, aristolochic acid, or p ‐bromophenacyl bromide, and the Ca 2+ ‐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 diacylglycerol (DAG) by DAG and monoacylglycerol lipases. The DAG lipase inhibitor, RHC‐80267 also blocked ATP‐stimulated PC secretion. The results suggest that both pathways for generating arachidonic acid via cPLA 2 and DAG lipase may participate in lung surfactant secretion. J. Cell. Biochem. 72:103–110, 1999. © 1999 Wiley‐Liss, Inc.