Reversible drug effects on the metabolic activation of polymorphonuclear leukocytes

Polymorphonuclear leukocytes (PMNs) stimulated by the chemotactic peptide formyl-methionyl-leucyl-phenylalanine (FMLP) were effectively inhibited by chlorpromazine (10 microM) and azelastine (20 microM) in terms of superoxide generation, and restored by the addition of dodecylbenzenesulfonic acid (DBS) in a range of concentrations from 20 to 40 microM. The stimulation of superoxide generation by DBS was also inactivated by dodecylamine (DA) but was restored by the subsequent addition of DBS. A dose dependent competitive inhibition and activation of leukocytes was observed between azelastine (10 microM) and DBS (20 microM). The release of arachidonic acid from leukocytes activated by the chemotactic peptide was decreased by DA or chlorpromazine, but could be restored by DBS. The changes in membrane potential of leukocytes as monitored by cyanine dye were also decreased by DA, chlorpromazine or azelastine. These observations indicate that some cationic drugs reversibly inhibit membrane bound enzymes or receptors. The physiological responses of these inhibited PMNs can then be restored by appropriate anionic amphiphiles.