Electrophysiological studies with new CCK analogs: correlation with binding affinity on B-type receptors.
The electrophysiological effects of Boc-D-Asp-Tyr(SO3H)-Nle-D-Lys-Trp-Nle-Asp-Phe-NH2 (compound I) and Boc-gamma-D-Glu-Tyr(SO3H)-Nle-D-Lys-Trp-Nle-Asp-Phe-NH2 (compound II), two cyclic cholecystokinin analogs with high selectivity for CCK-B receptors, as well as the effects of the linear enzyme-resistant analog Boc-[Nle28,Nle31]-CCK7 (BDNL), were compared with those of CCK8 using extracellular recordings in rat hippocampal slices in vitro. Bath applications of the three synthetic compounds resulted in concentration-dependent and reversible increases in single-unit activity. Comparison of equieffective concentrations yielded the following potency rank order: BDNL greater than CCK8 greater than compound II greater than compound I. There was a close correlation (r = .96, slope = 0.98) between the excitatory activities of the analogs and their potencies in displacing radiolabelled CCK8 from CCK-B receptors on rat brain membranes.
Böhme
G A
GA
Rhône-Poulenc Santé, Centre de Recherches de Vitry, France.
Durieux
C
C
Stutzmann
J M
JM
Charpentier
B
B
Roques
B P
BP
Blanchard
J C
JC
D000818:Animals; D001667:Binding, Competitive; D002540:Cerebral Cortex / Q000378:metabolism; D002766:Cholecystokinin / Q000031:analogs & derivatives* / Q000378:metabolism / Q000494:pharmacology*; D004594:Electrophysiology; D006624:Hippocampus / Q000187:drug effects / Q000502:physiology*; D008297:Male; D009474:Neurons / Q000187:drug effects / Q000502:physiology*; D010456:Peptides, Cyclic / Q000494:pharmacology; D051381:Rats; D011919:Rats, Inbred Strains; D011949:Receptors, Cholecystokinin / Q000187:drug effects / Q000378:metabolism*; D012016:Reference Values; D012844:Sincalide / Q000494:pharmacology; D013329:Structure-Activity Relationship
D010456:Peptides, Cyclic; D011949:Receptors, Cholecystokinin; D002766:Cholecystokinin; D012844:Sincalide