[Regulation by the protein kinase C activator phorbol ester of calcium channels in polymorphonuclear leukocytes]

The Quin fluorescence in gamma-hexachlorocyclohexane-stimulated polymorphonuclear leukocytes is rapidly increased, which points to the increase in Ca2+in concentration during leukotriene B4 synthesis in leukocytes. An addition of EGTA and calcium antagonists (nifedipine, verapamil, diltiazem) to cell suspensions does not affect the basal level of internal Ca2+ but results in the inhibition of the gamma-hexachlorocyclohexane-induced Ca2+ increase. Two mechanisms of calcium homeostasis regulation in neutrophils are proposed. One of them, cAMP regulation, is coupled with a potent inhibiting effect of prostacyclin, an adenylate cyclase activator, on Ca2+in increase in stimulated neutrophils. The other one is the activation of protein kinase C catalyzed by 4 beta-phorbol-12 beta-myristate-13 alpha-acetate. The experimental results suggest that such an activation blocks Ca2+ influx into the cells via the closure of Ca2+ channels. The synergism of action of the above mechanisms in the regulation of calcium homeostasis in neutrophils is demonstrated.