title: Cholecystokinin increases intracellular Ca2+ concentration in the Human JURKAT T Lymphocyte cell line.
abstract: We have recently demonstrated the presence of specific high-affinity cholecystokinin binding sites of the central type on the Human JURKAT T Lymphocyte Cell line. In this paper, changes in intracellular Ca2+ concentration ([Ca2+]i) in response to CCK (cholecystokinin) peptides were measured in the Human JURKAT T Lymphocyte Cell line by fura-2 fluorometry. CCK-8 (the C-terminal octapeptide of CCK), the potent CCK analog Boc-[Nle28,31]CCK-7, stimulated ([Ca2+]i) mobilization in a dose-dependent manner in cells preloaded with fura-2 AM with an EC50 of 2.4 +/- 1 nM and 8 +/- 2 nM, respectively. The selective CCKB receptor agonists, namely Boc-Trp-Nle-Asp-Phe-NH2 and the cyclic analog JMV320, [formula: see text], were also potent in stimulating mobilization of [Ca2+]i with an EC50 of 32 +/- 10 nM and 25 +/- 10 nM, respectively. Compound JMV180, Boc-Tyr(SO3H)-Nle-Trp-Nle-Asp-2-phenylethyl ester, did not stimulate [Ca2+]i but inhibited the mobilization of [Ca2+]i elicited by 10 nM CCK-8 in a dose-dependent manner with an IC50 of 10 +/- 2 nM. The selective non-peptide CCKB receptor antagonist L-365,260 was more potent than the selective CCKA receptor antagonist MK-329 in inhibiting the [Ca2+]i mobilization elicited by 10 nM CCK-8 with IC50 values of 20 +/- 8 nM and 400 +/- 100 nM, respectively. These data indicated that CCK-8 and potent CCK analogs induced [Ca2+]i mobilization in the Human JURKAT T cell line through the CCKB/gastrin receptor type.
authors.affiliation: Centre CNRS-INSERM de Pharmacologie-Endocrinologie, Faculté de Pharmacie, Montpellier, France.
authors.forename: M F
authors.initials: MF
authors.lastname: Lignon
authors.forename: N
authors.initials: N
authors.lastname: Bernad
authors.forename: J
authors.initials: J
authors.lastname: Martinez
mesh_terms: D000595:Amino Acid Sequence; D001570:Benzodiazepinones / Q000494:pharmacology; D002118:Calcium / Q000378:metabolism*; D003600:Cytosol / Q000378:metabolism; D020109:Devazepide; D016257:Fura-2; D006801:Humans; D008969:Molecular Sequence Data; D010671:Phenylurea Compounds; D011949:Receptors, Cholecystokinin / Q000037:antagonists & inhibitors / Q000378:metabolism*; D012844:Sincalide / Q000031:analogs & derivatives / Q000494:pharmacology*; D013601:T-Lymphocytes / Q000187:drug effects* / Q000378:metabolism; D014407:Tumor Cells, Cultured
chemical_list: D001570:Benzodiazepinones; D010671:Phenylurea Compounds; D011949:Receptors, Cholecystokinin; C058121:L 365260; D020109:Devazepide; D012844:Sincalide; D002118:Calcium; D016257:Fura-2