Inhibition of murine peritoneal macrophage functions by sulfated cholecystokinin octapeptide

Abstract

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.