Linking phospholipase A2 to phospholipid turnover and prostaglandin synthesis in mast cell granules.
Rapid incorporation of exogenous arachidonic acid into phospholipid has been detected in conjunction with eicosanoid synthesis by purified mast cell granules [Chock, S. P. & Schmauder-Chock, E. A. (1988) Biochem. Biophys. Res. Commun. 156, 1308-1315]. The species of phospholipid formed has now been identified primarily as phosphatidylinositol. A calcium-dependent phospholipase A2 has also been detected in the secretory granule. This enzyme, like the cyclooxygenase [Schmauder-Chock, E. A. & Chock, S. P. (1989) J. Histochem. Cytochem. 37, 1319-1328], appears to bind tightly to the granule matrix components. It is heat resistant and requires millimolar concentrations of calcium for optimal activity. It prefers phosphatidylinositol over phosphatidylcholine as substrate. Since the granule contains a large amount of phospholipid, the action of this phospholipase A2 can provide the required substrate for the arachidonic acid cascade. These findings provide the basis for linking phospholipase A2 to the production of eicosanoids during granule exocytosis. Since the granule also contains both an active acylating system that can rapidly reacylate lysophosphatidylinositol to form phosphatidylinositol, and an active phospholipase A2 which hydrolyzes phosphatidylinositol, a rapid turnover involving the fatty acid at the sn-2 position of phosphatidylinositol may occur. These findings are consistent with our postulation that the secretory granule is the source and/or the cause of many of the early biochemical events associated with the process of stimulus-secretion coupling.
Chock
S P
SP
Division of Experimental Therapeutics, Walter Reed Army Institute of Research, Washington, DC.
Rhee
S G
SG
Tang
L C
LC
Schmauder-Chock
E A
EA
D000818:Animals; D016718:Arachidonic Acid; D001095:Arachidonic Acids / Q000378:metabolism; D001345:Autoradiography; D002250:Carbon Radioisotopes; D003594:Cytoplasmic Granules / Q000378:metabolism*; D007700:Kinetics; D008297:Male; D008407:Mast Cells / Q000378:metabolism*; D010741:Phospholipases A / Q000378:metabolism*; D054467:Phospholipases A2; D010743:Phospholipids / Q000378:metabolism*; D011453:Prostaglandins / Q000096:biosynthesis*; D051381:Rats; D011919:Rats, Inbred Strains
D001095:Arachidonic Acids; D002250:Carbon Radioisotopes; D010743:Phospholipids; D011453:Prostaglandins; D016718:Arachidonic Acid; D010741:Phospholipases A; D054467:Phospholipases A2