Benoxaprofen activates membrane-associated oxidative metabolism in human polymorphonuclear leucocytes by apparent modulation of protein kinase C.

1. The non-steroidal anti-inflammatory drug (NSAID) benoxaprofen at concentrations of 15, 30 and 60 micrograms ml-1 caused a dose-related activation of superoxide generation by human polymorphonuclear leucocytes (PMNL) in vitro. 2. The protein kinase C (PKC) inhibitor H-7 prevented benoxaprofen-mediated activation of superoxide generation by PMNL. 3. Benoxaprofen, by apparent substitution for phosphatidylserine, caused a dose-related activation of purified PKC from rat brain and in cytosolic extracts from human platelets. 4. Benoxaprofen-mediated stimulation of PMNL membrane-associated oxidative metabolism is due to apparent activation of PKC by this NSAID. These findings establish the molecular basis of the pro-oxidative properties of benoxaprofen.