Pyrrophenone

The group IVA phospholipase A2 (PLA2), known as calcium-dependent cytosolic PLA2 (cPLA2), selectively releases arachidonic acid (AA) from membrane phospholipids, playing a central role in initiating the synthesis of prostaglandins (PGs) and leukotrienes (LTs).{11920,18018} Pyrrophenone inhibits cPLA2? with an IC50 of 4.2 nM in enzyme assays and potently blocks the release of AA and the production of PGE2 and LTC4 in cells (IC50 = 24, 25, and 14 nM, respectively).{17151} Its action is reversible and selective, as pyrrophenone inhibits the secretory type IB and IIA PLA2s with more than a hundred-fold less potency.{18019} Pyrrophenone has also been shown to inhibit calcium ionophore (A23187)-stimulated AA release from monocytic cells,{18019} interleukin-1-induced PGE2 synthesis in mesangial cells,{18019} and the production of PGE2, LTs, and platelet-activating factor by human neutrophils,{17152} always with maximal inhibition at concentrations below 1 ?M.