Interference of the calcium antagonists verapamil and nifedipine with lysosomal enzyme release from rabbit polymorphonuclear leukocytes

Abstract

Lysosomal enzyme release by exocytosis in rabbit polymorphonuclear leukocytes, induced by chemotactic peptide ionophore A 23187 or fluoride, is inhibited by high concentrations (0.2-1 mmol/l) of the calcium antagonists verapamil and nifedipine. Inhibition of enzyme release could be reversed by increasing the extracellular Ca2+-concentration. Verapamil and nifedipine also inhibited phagocytosis of opsonized zymosan and concomitant release of lysosomal enzymes. Inhibition of phagocytosis occurred at lower concentrations as compared with inhibition of enzyme release induced by non-particulate agents. Nifedipine is a stronger inhibitor than verapamil as regards phagocytosis and enzyme release induced by A 23187 as well as chemotactic peptide, but with respect to fluoride-induced enzyme release verapamil was stronger inhibitor. It is concluded that verapamil and nifedipine interfere with Ca2+-transport across the membrane, or with an intracellular Ca2+-requiring process that can be modulated by extracellular Ca2+.