THE INHIBITION EFFECT OF CHOLECYSTOKININ IN HUMAN COLONIC LAMINA PROPRIA LYMPHOCYTE-PROLIFERATION, AND REVERSAL BY THE CHOLECYSTOKININ RECEPTOR ANTAGONIST L-364718

Cholecystokinin (CCK) is a potent neuropeptide hormone with activity on various gastrointestinal organs during the digestive process. It was recently suggested that CCK may also act on the immune system. In this study we investigated the effect of CCK on the human mucosal immune system as represented by colonic lamina propria lymphocytes (LPL). Our results demonstrate that CCK at concentrations of 10(-13)M to 10(-7)M inhibits thymidine incorporation into Con A-stimulated LPL DNA by up to 40%. Moreover, this inhibitory effect was reversed by the specific CCK receptor antagonist, L-364718, at concentrations of 10(-8)M to 10(-5)M. In addition, CCK did not affect DNA synthesis of LPL stimulated with phorbol ester (PDB) and calcium inophore (ionomycin). It is postulated that the CCK effect may involve intracellular metabolic steps proximal to protein kinase C activation and calcium flux. Our results suggest that CCK may play a role in modulating the human mucosal immune system during digestion and thus, should be added to the list of the neuropeptides that affect the mucosal immune system.