MODULATION OF MURINE LYMPHOCYTE FUNCTIONS BY SULFATED CHOLECYSTOKININ-OCTAPEPTIDE

The effects in vitro of the sulfated octapeptide form of cholecystokin in (CCK-8) at concentrations ranging from 10(-13) M to 10(-6) M on sev eral functions of murine lymphocytes were studied, i.e. adherence to s ubstrate, mobility (spontaneous and directed by chemical gradient or c hemotaxis) and spontaneous and phytohemagglutinin (PHA)mediated prolif eration. Lymphocytes were obtained from peritoneal suspension as well as from axillary nodes, spleen and thymus of BALB/c mice. CCK-8, at co ncentrations from 10(-10) M to 10(-8) M, significantly inhibited the m obility capacity and the PHA-induced proliferation and increased the a dherence and the spontaneous proliferation of lymphocytes. A dose-resp onse relationship was observed, with a maximum effect on lymphocyte fu nctions at 10(-10) M. In addition, CCK-8 induced a significant decreas e in membrane and cytosol protein kinase C (PKC) activity in murine ly mphocytes, as well as an increase of intracellular cyclic AMP levels. These results suggest that CCK-8 is a negative modulator of two import ant lymphocyte functions in the immune response, i.e. mobility and mit ogen-induced proliferation, and that the PKC activity inhibition and c AMP increase could be the mechanisms through which CCK inhibits these lymphocyte activities.