Pituitary adenylate cyclase-activating polypeptide (PACAP-38) stimulates rat peritoneal macrophage functions

The present study shows that PACAP-38, in a dose-dependent manner, increased in vitro two steps of the phagocytic process in rat peritoneal macrophages: ingestion of inert particles (latex beads) and production of superoxide anion as measured by nitroblue tetrazolium reduction. The most effective concentration of PACAP-38 was 10(-10) M. Similarly, PMA, an activator of protein kinase C (PKC), increased the phagocytic activity in a dose-dependent manner, whereas retinal, a PKC inhibitor, decreased the activity. Macrophages incubated with forskolin, an enhancer of intracellular cAMP levels, produced an inhibitory effect on both phagocytic functions. The maximum stimulation of the phagocytic activity by PACAP-38 was not further enhanced by addition of PMA, suggesting that the enhancement of the phagocytic activity by PACAP-38 and PMA is mediated by a common signaling pathway. In addition, retinal as well as forskolin inhibited partially the stimulatory effect that PACAP-38 produced in the macrophage functions studied. Furthermore, this study showed that a VIP receptor antagonist was unable to suppress the stimulatory effect of PACAP-38. These results could prove that PACAP-38 stimulates the phagocytosis and production of superoxide anion in macrophages through PKC activation by binding to type I PACAP receptor.