EFFECT OF CHOLECYSTOKININ RECEPTOR BLOCKADE ON HUMAN LYMPHOCYTE-PROLIFERATION

Cholecystokinin is a peptide produced by neuroendocrine cells in gut and neurons in brain and gut. Proliferating human peripheral blood mononuclear cells (HPBMC) also make small amounts of cholecystokinin. Cholecystokinin increases intracellular calcium (Ca2+) in H-PBMC. This can be blocked with L 364, 718, a non-toxic specific cholecystokinin antagonist. Cholecystokinin is a comitogen for H-PBMC and activates H-PBMC in a cyclosporine-resistant fashion. If cholecystokinin is a critical lymphokine, then L 364, 718 should block H-PBMC mitogenesis. H-PBMC from healthy donors were stimulated in vitro with either phytohemagglutinin or anti-CD3 monoclonal antibody. L 364,718 was not toxic for H-PBMC, yet inhibited mitogenesis at 10-7, 10-8, and 10-5 M. The small amount of cholecystokinin made by H-PBMC may play a critical role in H-PBMC mitogenesis. © 1990.