Inhibition of murine peritoneal macrophage functions by sulfated cholecystokinin octapeptide

The effect in vitro of the sulfated octapeptide form of cholecystokinin, CCK-8, at concentrations from 10(-12) M to 10(-6) M on several functions of resting peritoneal macrophages from BALB/c mice: adherence to substrate, mobility (spontaneous and directed by chemical gradient or chemotaxis), ingestion of inert particles (latex beads) or cells (Candida albicans), and production of superoxide anion measured by nitroblue tetrazolium reduction was studied. CCK-8, at concentrations from 10(-10) M to 10(-8) M, inhibited significantly all functions studied with the exception of adherence to substrate, which was increased. A dose-response relationship was observed, with a maximum inhibition of macrophage functions found at 10(-8) M. This neuropeptide induced in murine macrophages a significant, but transient, increase of cAMP levels at 60 sec. On the contrary, CCK-8 produced a slight but significant decrease of protein kinase C (PKC) activity at 5 min of incubation. These results suggest that CCK-8 is a negative modulator of several macrophage functions, and that the inhibition of these activities is carried out through an increase of intracellular cAMP levels and a decrease in PKC activity.