Potentiation and inhibition of secretion from neutrophils by phorbol ester

We demonstrate that PMA exhibits multiple effects on fMetLeuPhe and ionophore-mediated secretion from rabbit and human neutrophils: Inhibition of receptor-mediated secretion appears to take place at an early stage in the stimulus-secretion coupling sequence since PMA inhibits the formation of phosphatidate. Protein phosphorylation is observed with both PMA and fMetLeuPhe and the extent of phosphorylation is additive in the presence of both stimuli. Another possible site of regulation by PMA lies distal to the rise in cytosolic Ca2+. This is indicated by the enhancement of inhibition by PMA of the A23187-induced secretory response at low and high external Ca2+ concentrations, respectively.