CINCHOCAINE AND AMETHOCAINE INHIBIT ACTIVATION AND ACTIVITY OF SUPEROXIDE PRODUCTION IN HUMAN NEUTROPHILS

Stimulation of neutrophils by either phagocytable particles or soluble agonists provokes an active production of superoxide, a substance which has an important antimicrobial role and is also important in the pathogenesis of the adult respiratory distress syndrome (Babior, 1984; Brigham and Meyrick, 1984). A plasma membrane-associated NADPH oxidase, dormant in resting cells, is responsible for catalytic activity that produces superoxide (Badwey and Karnovsky, 1980). However, the signal transmission mechan-isms for superoxide production still require elucidation. Phosphatidylinositol turnover (Serhan et al., 1983), mobilization of membrane-associated calcium (Takeshige et al., 1980), an increase in the cytosolic free calcium concentration (Nakagawara et al., 1984), calmodulin (Takeshige and Minakami, 1981) and calcium-activated phospholipid-dependent protein kinase (C-kinase) (Fujita et al., 1984) are thought to be involved. Among many stimuli which induce superoxide production, phorbol 12-myristate 13-acetate (PMA) and l-oleoyl-2-acetyl-glycerol (OAG) are characteristic, because both have been reported to activate C-kinase in the absence of diacylglycerol in vitro (Castagna et al., 1982; Kaibuchi et al., 1982). In neutrophils these stimuli induce neither phosphatidylinositol turnover (Serhan et al., 1983) nor an increase in the cytosolic free calcium concentration (Fujita et al., 1984). We have previously shown that protein (de)phosphorylation is associated with the activation of pig neutrophil