CCK antagonists interact with CCK-B receptors on human small cell lung cancer cells.
The ability of cholecystokinin (CCK) receptor antagonists to interact with CCK receptors in small cell lung cancer (SCLC) cells was investigated. L-365,260, CCK-8, L-364,718, CBZ-CCK(27-32)-NH2 and proglumide analogue 10 inhibited specific 125I-CCK-8 binding to SCLC cells with IC50 values of 0.2, 2, 500, 100,000 and 500,000 nM, respectively. Gastrin-I and CCK-8 elevated the cytosolic Ca2+ when SCLC cells were loaded with Fura 2-AM. L-365,260 inhibited the cytosolic Ca2+ increase caused by 10 nM CCK-8 in a dose-dependent manner. The effects of 10 nM L-365,260 were reversed by high concentrations of CCK-8. These data indicate that L-365,260 functions as a reversible CCK-8 antagonist using SCLC cells.
Staley
J
J
Department of Biochemistry and Molecular Biology, George Washington University School of Medicine and Health Sciences, Washington, DC 20037.
Jensen
R T
RT
Moody
T W
TW
D001570:Benzodiazepinones / Q000378:metabolism / Q000494:pharmacology; D001667:Binding, Competitive; D002118:Calcium / Q000378:metabolism; D018288:Carcinoma, Small Cell / Q000473:pathology*; D002766:Cholecystokinin / Q000031:analogs & derivatives / Q000037:antagonists & inhibitors* / Q000378:metabolism / Q000494:pharmacology; D020109:Devazepide; D005755:Gastrins / Q000494:pharmacology; D006801:Humans; D008175:Lung Neoplasms / Q000473:pathology*; D010446:Peptide Fragments / Q000378:metabolism / Q000494:pharmacology; D010671:Phenylurea Compounds; D011377:Proglumide / Q000031:analogs & derivatives / Q000378:metabolism / Q000494:pharmacology; D011949:Receptors, Cholecystokinin / Q000187:drug effects* / Q000378:metabolism; D012844:Sincalide / Q000378:metabolism*; D014407:Tumor Cells, Cultured / Q000187:drug effects / Q000378:metabolism
D001570:Benzodiazepinones; C067239:CR 1407; D005755:Gastrins; D010446:Peptide Fragments; D010671:Phenylurea Compounds; D011949:Receptors, Cholecystokinin; C058121:L 365260; D002766:Cholecystokinin; C058798:cholecystokinin (27-32) amide, benzoyloxycarbonyl-; D011377:Proglumide; D020109:Devazepide; D012844:Sincalide; D002118:Calcium