Modulation of murine lymphocyte functions by sulfated cholecystokinin octapeptide

The effects in vitro of the sulfated octapeptide form of cholecystokinin (CCK-8) at concentrations ranging from 10(-13) M to 10(-6) M on several functions of murine lymphocytes were studied, i.e. adherence to substrate, mobility (spontaneous and directed by chemical gradient or chemotaxis) and spontaneous and phytohemagglutinin (PHA)-mediated proliferation. Lymphocytes were obtained from peritoneal suspension as well as from axillary nodes, spleen and thymus of BALB/c mice. CCK-8, at concentrations from 10(-10) M to 10(-8) M, significantly inhibited the mobility capacity and the PHA-induced proliferation and increased the adherence and the spontaneous proliferation of lymphocytes. A dose-response relationship was observed, with a maximum effect on lymphocyte functions at 10(-10) M. In addition, CCK-8 induced a significant decrease in membrane and cytosol protein kinase C (PKC) activity in murine lymphocytes, as well as an increase of intracellular cyclic AMP levels. These results suggest that CCK-8 is a negative modulator of two important lymphocyte functions in the immune response, i.e. mobility and mitogen-induced proliferation, and that the PKC activity inhibition and cAMP increase could be the mechanisms through which CCK inhibits these lymphocyte activities.