Satiety signals in sheep: involvement of CCK, propionate, and vagal CCK binding sites

The satiety effects of the hormone, cholecystokinin (CCK), and propionate, an important gluconeogenic substrate, were studied in ad lib-fed sheep. Hepatic portal infusion of either sodium propionate (1.2 mmol/min) or sulphated CCK-8 (sCCK-8; 18.3 pmol/kg/min) had no effect on food intake. However, together, they decreased intake by 44%; similar to the effect of 2.4 mmol/min propionate alone. CCK infusions reduced the frequency of reticular contractions in the presence or absence of propionate. The effects of infusions on motility and food intake were, therefore, dissociated. Further studies demonstrated axonal transport of CCK binding sites in the ovine vagus. Binding sites accumulated to a similar extent on both sides of a ligature indicating the existence of both anterograde and retrograde transport which was limited to a small proportion of fibres. Binding incubations carried out in the presence of the CCK receptor antagonists, MK-329 and L-365,260, indicated that the majority of binding sites, if not the total population, possessed pharmacology typical of type B CCK receptors.