The role of the Val353 residue in antagonist binding to rat CCK-B receptors.
The Val353 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 radioligand [3H]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 the affinity of the peptoid CCK-B receptor antagonist Cam-1028. The results show that Val353 is not part of a general CCK-B receptor antagonist recognition site and that Cam-1028 is recognized at a receptor site distinct from that binding asperlicin derivatives.
Malatynska
E
E
Department of Pharmacology, University of Arizona Health Sciences Center, Tucson 85724, USA.
Knapp
R J
RJ
Stropova
D
D
Varga
E
E
Yamamura
H I
HI
D000596:Amino Acids / Q000494:pharmacology; D000818:Animals; D001667:Binding, Competitive; D004305:Dose-Response Relationship, Drug; D009154:Mutation; D010446:Peptide Fragments / Q000494:pharmacology; D034444:Peptoids; D051381:Rats; D011919:Rats, Inbred Strains; D011949:Receptors, Cholecystokinin / Q000037:antagonists & inhibitors* / Q000187:drug effects*; D012844:Sincalide / Q000031:analogs & derivatives / Q000494:pharmacology; D014633:Valine / Q000494:pharmacology*
D000596:Amino Acids; D010446:Peptide Fragments; D034444:Peptoids; D011949:Receptors, Cholecystokinin; C066684:SNF 8702; D014633:Valine; D012844:Sincalide