Characterization of the novel CCK analogs JMV-180, JMV-320, and JMV-332 in H345 cells.
The interaction of the novel CCK analogs JMV-180, JMV-320, and JMV-332 with CCK-B/gastrin receptors on small cell lung cancer (SCLC) cells was investigated. JMV-180, JMV-320, and JMV-332 potently inhibited specific binding of 125I-CCK-8 to CCK-B/gastrin receptors expressed on the SCLC cell line NCI-H345 (H345) with IC50 values of 4.9, 1.8, and 7.0 nM, respectively. JMV-320 and JMV-332 stimulated intracellular calcium ([Ca2+]i) release in a dose-dependent manner in cells preloaded with indo-1. JMV-180 did not stimulate [Ca2+]i but inhibited the [Ca2+]i release elicited by 10 nM CCK-8 in a dose-dependent manner. These data indicate that JMV-320 and JMV-332 function as CCK-B/gastrin receptor agonists while JMV-180 functions as a CCK-B/gastrin receptor antagonist in H345 cells.
Witte
D G
DG
Neuroscience Research Division, Abbott Laboratories, Abbott Park, IL 60064.
Nadzan
A M
AM
Martinez
J
J
Rodriguez
M
M
Lin
C W
CW
D000595:Amino Acid Sequence; D018288:Carcinoma, Small Cell / Q000737:chemistry*; D002766:Cholecystokinin / Q000031:analogs & derivatives* / Q000032:analysis; D008175:Lung Neoplasms / Q000737:chemistry*; D008969:Molecular Sequence Data; D011949:Receptors, Cholecystokinin / Q000037:antagonists & inhibitors / Q000187:drug effects*; D012844:Sincalide / Q000031:analogs & derivatives / Q000032:analysis; D014407:Tumor Cells, Cultured
D011949:Receptors, Cholecystokinin; C058451:JMV 180; C075380:JMV 320; C079583:JMV 332; D002766:Cholecystokinin; D012844:Sincalide