CCK-JMV-180 ACTS AS AN ANTAGONIST OF THE CCKA RECEPTOR IN THE HUMAN IMR-32 NEUROBLASTOMA CELL-LINE

[I-125]Cholecystokinin-8-S (CCK-8-S) bound to a single class of satura ble binding sites on the human neuroblastoma cell line IMR-32 (K-D = 4 +/- 1.5 nM, B-max = 10,500 +/- 3,500 sites/cell (n = 6)). These bindi ng sites were of the CCKA type, as demonstrated by the differential in hibition of the binding of [I-125]CCK-8-S and CCK-8-S-induced Ca-45(2) efflux by the specific CCKA antagonist SR 27897 and the specific CCK B antagonist PD 134,308. CCK-JMV-180, an analogue of CCK-8-S which has been shown to activate Ca-45(2+) efflux in rat cells in a manner simi lar to CCK-8-S, acted as a potent antagonist of CCK-8-S-induced Ca-45( 2+) efflux (IC50 = 50 nM) and inhibited [I-125]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 o f CCKA receptors in the human neuroblastoma cell line IMR-32.