Lipocortin I and lipocortin II inhibit phosphoinositide‐ and polyphosphoinositide‐specific phospholipase C The effect results from interaction with the substrates

Lipocortins I and II, known to inhibit phospholipase A 2 , have been purified from bovine lung and tested with respect to their ability to affect the enzymatic activities of phosphoinositide‐ and polyphosphoinositide‐specific phospholipase C from human platelets, rat liver cytosol or rat brain membranes. At 0.67,μM, both lipocortins led to complete inhibition of phospholipase C activity with either phosphatidylinositol or phosphatidylinositol 4,5‐bisphophate as substrate. The inhibition could be overcome by increasing the substrate concentration. Ultracentrifugation studies with lipocortin II showed a direct interaction between phosphatidylinositol and the lipocortin, indicating that the lipocortins inhibit phospholipase C not directly but by interacting with the substrate. In experiments with plasma membranes from [ 3 H]inositol‐labeled HL‐60 cells, lipocortin II did not affect PI‐specific phospholipase C activity in the absence or presence of calcium plus or minus GTP‐γ‐S.