CCK-JMV-180 acts as an antagonist of the CCKA receptor in the human IMR-32 neuroblastoma cell line

Abstract [ 25 I]Cholecystokinin-8-S (CCK-8-S) bound to a single class of saturable 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 binding sites were of the CCK A type, as demonstrated by the differential inhibition of the binding of [ 125 I]CCK-8-S and CCK-8-S-induced 45 Ca 2+ efflux by the specific CCK A 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 45 Ca 2+ efflux in rat cells in a manner similar to CCK-8-S, acted as a potent antagonist of CCK-8-S-induced 45 Ca 2+ efflux (IC 50 = 50 nM) and inhibited [ 125 I]CCK-8-S binding to IMR-32 cells (IC 50 = 1.7 nM). These results show that, unlike its CCK-like effect in various animal systems, CCK-JMC-180 acts as an antagonist of CCK A receptors in the human neuroblastoma cell line IMR-32.