Differential effects of CCK-JMV-180 on food intake in rats and mice

Boc-Tyr(SO3)-Nle-Gly-Trp-Nle-Asp-2-phenylether ester (CCK-JMV-180) has been reported to be a CCK-based heptipeptide with novel in vitro properties. Based on studies conducted in rat and mouse pancreatic acini, it has been proposed that the compound acts as an agonist the high-affinity site and an antagonist at the low-affinity site in the rat, but as an agonist at both sites in the mouse. In the present study, we examined the effects of CCK-JMV-180 on locomotor activity in the rat and on intake of a liquid diet in the rat and mouse. Although CCK-JMV-180 slightly reduced activity on its own in the rat, it completely reversed the suppression produced by coadministration of CCK-8. In rat feeding studies, CCK-JMV-180 failed to suppress intakes of a liquid diet, but was able to antagonize the anorectic effects of CCK-8. In contrast, in the mouse CCK-JMV-180 potently suppressed intakes on its own, and this effect was blocked by pretreatment with the selective CCK-A receptor antagonist, A-70104. The results of these studies suggest that similar receptor mechanisms are involved in CCK's ability to inhibit food intake in vivo and its effects on pancreatic function in vitro.