A cholecystokinin agonist/antagonist according to dose and time of action: effect on food intake

A new CCK pseudopeptide (Boc-Tyr (SO3)-Nle-psi-(COCH2) Gly-Trp-Nle-Asp-Phe-NH2) has been described in a previous study as a potent CCK agonist in the peripheral system and as an antagonist in the central nervous system. When administered alone by a peripheral route, this pseudopeptide was found to decrease food intake in free/feeding rats, and thus behaved as a CCK agonist. However, it reversed the decreased feeding effect induced by a full potent agonist (Boc(Nle 28-Nle 31)-CCK26-33). This antagonistic action occurred 3-4 h after treatment, at a time when the agonistic properties of the pseudopeptide alone had disappeared, but when the effect of the full potent agonist remained. The dose-response curve of the antagonistic action was bell-shaped. These results suggest that this new pseudopeptide is not only agonistic in the periphery and antagonistic in the central nervous system as shown in the previous study, but is also both agonistic and antagonistic on the same paradigm according to the dose and time of action.