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 (H-PBMC) 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(-6), and 10(-5) M. The small amount of cholecystokinin made by H-PBMC may play a critical role in H-PBMC mitogenesis.