THE ROLE OF THE VAL(353) RESIDUE IN ANTAGONIST BINDING TO RAT CCK-B RECEPTORS

THE Val(353) residue of the rat cholecystokinin-B (CCK-B) receptor was mutated to Leu to test whether this residue is part of a binding site for antagonists having different chemical structures. The agonist rad ioligand [H-3]SNF 8702 showed similar affinity for both wild-type and mutant receptors. Mutation of the CCK-B receptor reversed the order of affinities for the asperlicin derivatives from L-365,260 > devazepide (wild-type) to devazepide > L-365,260 (mutant) but had no effect on t he affinity of the peptoid CCK-B receptor antagonist Cam-1028. The res ults show that Val(353) is not part of a general CCK-B receptor antago nist recognition site and that Cam-1028 is recognized at a receptor si te distinct from that binding asperlicin derivatives.