The differential effects of nedocromil sodium and sodium cromoglycate on the secretory response of rabbit peritoneal neutrophils.

Activation of neutrophils, through the formation of inositol triphosphate (IP3) and diacylglycerol, results in lysosomal enzyme secretion, a release process which involves calcium and protein kinase C. Rabbit peritoneal neutrophils were used in this study to compare the effects of nedocromil sodium cromoglycate on enzyme release and IP3 accumulation induced by the activators fMLP (a chemotactic peptide which generates diacylglycerol and produces a rise in cytosolic Ca2+) and phorbol dibutyrate (PDBu), which activates only protein kinase C. Both drugs produced a small but significant (p less than 0.05) inhibition of fMLP-induced lysozyme secretion. With PDBu-induced enzyme secretion, however, nedocromil sodium caused a 25% decrease in the secretory response whilst sodium cromoglycate had no effect, suggesting that the two compounds have different mechanisms of action or that nedocromil sodium has an additional mode of action not shown by sodium cromoglycate. In addition, nedocromil sodium did not block fMLP-induced IP3 accumulation. These results indicate that nedocromil sodium inhibits the secretory response of neutrophils via an effect on protein kinase C rather than on calcium homeostasis.