CHLORPROMAZINE INHIBITION OF GRANULOCYTE SUPEROXIDE PRODUCTION
- 1 January 1980
- journal article
- research article
- Vol. 56 (1), 23-29
Abstract
Superoxide production by granulocytes is a result of the activation of an NAD(P)H-dependent oxidase present in the plasma membrane. Chlorpromazine [an anesthetic] (5-50 .mu.M) prolongs the time necessary for activation of the superoxide generating system and inhibits the extent of activation. When chlorpromazine is added after activation, there is an inhibition of further superoxide production. These effects are seen with digitonin, phorbol myristate acetate and opsonized zymosan stimulated guinea pig and human granulocytes. Other phenothiazines [trifluoperazine and prochlorperazine] (1-20 .mu.M) and tetracaine (0.1-1.0 mM) produce similar effects. Lidocaine (1-10 mM) inhibits superoxide production, but has no effect on the rate of activation. The effect of chlorpromazine on the rate of activation is reversible, but its effect on extent of activation is unaffected by extensive washing. Incubation of granulocytes with chlorpromazine results in decreased activation of the plasma membrane superoxide generating NADPH oxidase. Chlorpromazine also competes with NADPH for the membrane oxidase. These data and previously published results provide the basis of a model for the activation of the superoxide generating system.This publication has 23 references indexed in Scilit:
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