Depression of Ca<SUP>2&#8290;</SUP> Influx in Complement C5a-stimulated Neutrophils by Calmodulin Inhibitors

Depression of Ca<SUP>2&#8290;</SUP> Influx in Complement C5a-stimulated Neutrophils by Calmodulin Inhibitors

Role of Ci+jcalmodulin complex in intracellular Ca2 十 mobilization in neutrophils has not been c1ear1y elucidated. In this study， effects of ch1orpromazine， trifluoperazine and imipramine on the intracellular Ca2+ mobilization， inc1uding Ca2+ influx， in C5a-activated neutrophils were investigated. Complement C5astimulated superoxide production and mye1operoxidase release in neutrophils were inhibited by ch1orpromazine，tr‘ifluoperazine and imipramine， except no effect of imipramine on myeloperoxidase release. A C5a-elicited elevation of [Ca ]i 2十 in neutrophils was inhibited by ch1opromazine， trifluoperazine，imipramine，staurosporine， genistein， EGT A， and verapami1 but not affected by pertussis toxin. The intracellular‘ Ca2+ release in C5a-activated neutrophils was not affected by ch1orpromazine and imipramine. Ch1orpromazine and imipramine inhibited Mn2+influx by C5a-activated neutrophils. Thapsigargin-evoked Ca entry was inhibited by ch1orpromazine， trifluoperazine， imipramine， genistein， EGT A and verapamil， while the effect of staurosporine was not detected. The resu1ts suggest that Ca2 十jcalmodulin complex is involved in the activation process of neutrophils. The depressive action of calmodulin inhibitors on the elevation of cytosolic Ca2+ level in C5a-activated neutrophils appears to be accomplished by inhibition of Ca2+ influx from the extracellular medium.