Hepatic-portal infusion reduces the satiating potency of CCK-8

If a satiating effect of endogenous cholecystokinin (CCK) is produced through a circulating hormonal mechanism, then administration of exogenous CCK into the hepatic-portal vein should decrease meal size. We report here that when doses of CCK-8 are injected intraperitoneally, they are at least four times more potent at reducing food intake than equivalent doses infused into the hepatic-portal vein. Intraportally administered CCK-8 at a dose of 32 micrograms.kg-1 had an equivalent satiating potency to 4 micrograms.kg-1 administered intraperitoneally. In contrast, intraportal infusions of the putative satiety hormone, tetradecapeptide bombesin, were equally as effective as intraperitoneal injections for reducing food intake. Bombesin is apparently protected from significant hepatic uptake by its larger size. We conclude that the primary reason for the ineffectiveness of portally administered CCK-8 for reducing food intake is hepatic uptake. These findings support the hypothesis that any satiating effect of endogenous CCK-8 is likely to act primarily through a paracrine mechanism.