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.
Ferrara
A
A
Gastrointestinal Surgical Research Group, Yale University School of Medicine, New Haven, Connecticut 06520.
McMillen
M A
MA
Schaefer
H C
HC
Zucker
K A
KA
Modlin
I M
IM
D000911:Antibodies, Monoclonal; D015703:Antigens, CD / Q000276:immunology; D001570:Benzodiazepinones / Q000494:pharmacology; D002455:Cell Division; D002766:Cholecystokinin / Q000037:antagonists & inhibitors; D020109:Devazepide; D006801:Humans; D008214:Lymphocytes / Q000166:cytology* / Q000378:metabolism; D010835:Phytohemagglutinins; D011949:Receptors, Cholecystokinin / Q000502:physiology*; D013936:Thymidine / Q000378:metabolism
D000911:Antibodies, Monoclonal; D015703:Antigens, CD; D001570:Benzodiazepinones; D010835:Phytohemagglutinins; D011949:Receptors, Cholecystokinin; D002766:Cholecystokinin; D020109:Devazepide; D013936:Thymidine