CCK-JMV-180 acts as an antagonist of the CCKA receptor in the human IMR-32 neuroblastoma cell line.
[125I]Cholecystokinin-8-S (CCK-8-S) bound to a single class of saturable binding sites on the human neuroblastoma cell line IMR-32 (KD = 4 +/- 1.5 nM, Bmax = 10,500 +/- 3,500 sites/cell (n = 6)). These binding sites were of the CCKA type, as demonstrated by the differential inhibition of the binding of [125I]CCK-8-S and CCK-8-S-induced 45Ca2+ efflux by the specific CCKA antagonist SR 27897 and the specific CCKB antagonist PD 134,308. CCK-JMV-180, an analogue of CCK-8-S which has been shown to activate 45Ca2+ efflux in rat cells in a manner similar to CCK-8-S, acted as a potent antagonist of CCK-8-S-induced 45Ca2+ efflux (IC50 = 50 nM) and inhibited [125I]CCK-8-S binding to IMR-32 cells (IC50 = 1.7 nM). These results show that, unlike its CCK-like effect in various animal systems, CCK-JMC-180 acts as an antagonist of CCKA receptors in the human neuroblastoma cell line IMR-32.
Schaeffer
P
P
Haemobiology Research Department, Sanofi Recherche, Toulouse, France.
Prabonnaud
V
V
Roux
M
M
Gully
D
D
Herbert
J M
JM
D002132:Calcium Radioisotopes / Q000378:metabolism; D006801:Humans; D007700:Kinetics; D009447:Neuroblastoma / Q000378:metabolism*; D011949:Receptors, Cholecystokinin / Q000037:antagonists & inhibitors* / Q000378:metabolism; D012844:Sincalide / Q000031:analogs & derivatives* / Q000378:metabolism / Q000494:pharmacology; D014407:Tumor Cells, Cultured
D002132:Calcium Radioisotopes; D011949:Receptors, Cholecystokinin; C058451:JMV 180; D012844:Sincalide