Description
The group IVA phospholipase A
2 (PLA
2), known as calcium-
dependent cytosolic PLA
2 (cPLA
2), selectively releases arachidonic acid (AA) from membrane phospholipids, playing a central role in initiating the synthesis of prostaglandins (PGs) and leukotrienes (LTs). Pyrrophenone inhibits cPLA
2α with an IC
50 of 4.2 nM in enzyme assays and potently blocks the release of AA and the production of PGE
2 and LTC
4 in cells (IC
50 = 24, 25, and 14 nM, respectively). Its action is reversible and selective, as pyrrophenone inhibits the secretory type IB and IIA PLA
2s with more than a hundred-
fold less potency. Pyrrophenone has also been shown to inhibit calcium ionophore (A23187)-
stimulated AA release from monocytic cells, interleukin-
1-
induced PGE
2 synthesis in mesangial cells, and the production of PGE
2, LTs, and platelet-
activating factor by human neutrophils, always with maximal inhibition at concentrations below 1 μM.
