Halothane, an inhalation anesthetic, activates protein kinase C and superoxide generation by neutrophils

Abstract
The rate of superoxide generation of guinea pig intraperitoneal neutrophils by a chemotactic peptide or 12‐O‐tetradecanoylphorbol‐13‐acetate (TPA) was increased by 2‐bromo‐2‐chloro‐1,1,1,‐trifluoroethane (halothane), an inhalation anesthetic. This increase was inhibited by 1‐(5‐isoquinolinesulfonyl)methylpiperazine dihydrochloride (H‐7), a specific inhibitor of Ca2+‐ and phospholipid‐dependent protein kinase C (PKC). Halothane was found to significantly activate partially purified PKC. The activation required phosphatidylserine (PS) and Ca2+. Dioleoylglycerol‐ or TPA‐activated PKC activity was further increased by halothane. The cytoplasmic proteins of guinea pig neutrophils phosphorylated by halothane‐activated PKC were similar to those phosphorylated by PMA‐activated PKC. The phosphorylation of a 48 kDa protein, a phosphorylated protein required for NADPH oxidase activation, was also increased by halothane. These data suggest that the increase of superoxide production by halothane is correlated with its activation of PKC.