Regulation by Protein Kinase C of Platelet-Activating Factor- and Thapsigargin-Induced Calcium Entry in Rabbit Neutrophils

Abstract

12-O-Tetradecanoylphorbol-13-acetate (TPA) time-dependently inhibited the platelet-activating factor (PAF)-induced rise in cytosolic free calcium concentration ([Ca²⁺]_i) in rabbit neutrophils, whereas staurosporine significantly enhanced it. Inositol 1, 4, 5-trisphosphate (IP₃) induced Ca²⁺ release in digitonin-permeabilized cells but not in PAF-pretreated permeabilized cells. IP₃-induced Ca²⁺ release was not affected by protein kinase C activators or inhibitors. In the cells pretreated with PAF and thapsigargin in Ca²⁺-deficient medium, stimulated Ca²⁺ entry was evoked by the subsequent addition of CaCl₂. TPA inhibited the Ca²⁺ entry induced by PAF and thapsigargin in a staurosporine-reversible manner but not thapsigargin-induced [Ca²⁺]_i elevation. These results suggest that protein kinase C negatively regulates PAF- and thapsigargin-induced rise in [Ca²⁺]_i possibly by inhibiting Ca²⁺ store depletion-induced Ca²⁺ entry.