Multiple affinity states of different cholecystokinin receptors

Abstract

We transfected COS cells with cDNA for rat cholecystokinin-A (CCK-A) and different CCK-B receptors and measured binding of 125I-CCK-8, [3H]L-364,718 and [3H]L-365,260 to characterize the different affinity states for each type of CCK receptor. Rat CCK-A and CCK-B receptors, canine CCK-B receptors and canine mutant CCK-B (M-CCK-B) receptors in which the leucine in position 355 was replaced by valine each existed in three different affinity states for CCK-8, high affinity, low affinity, and very low affinity. In rat CCK-A and probably CCK-B receptors, most were in the very low affinity state, whereas with canine CCK-B and M-CCK-B receptors, most were in the low affinity state. Studies with CCK receptor agonists, CCK-8, gastrin, and CCK-JMV-180, in conjunction with CCK receptor antagonists, L-364,718 and L-365,260, showed a different pattern of affinities for these ligands at the different CCK receptors. Thus, each transfected CCK receptor can exist in three different affinity states for CCK-8 and has a characteristic pattern of interaction with different ligands. This ability to exist in multiple affinity states is an intrinsic property of the CCK receptor molecule itself.