Peptides with CCK-like activity administered intracranially elicit satiety in sheep

Cholecystokinin (CCK) peptides and receptors have been shown to be present in the brain as well as in gastrointestinal organs. While functions for peripheral CCK are well recognized, those for central CCK peptides are only now being investigated. We have shown previously that CCK-octapeptide (CCK-OP) is a very potent and specific suppressor of feeding when administered in the cerebral ventricles of sheep. In the present study the objective was to determine the relative potency of several CCK analogues in inhibiting feeding when administered as 75 min continuous injections into the lateral cerebral ventricles of 2-hr fasted sheep. In comparing feeding response during CCK-OP injections to that during caerulein injections, it was found that feed intakes were similar only at an equal molar dose (0.638 pmole/min); whereas three times as much CCK-33 (1.91 pmoles/min) as CCK-OP (0.638 pmoles/min) was required to produce similar feed intakes. Both caerulein (0.638 pmoles/min) and CCK-33 (1.91 pmoles/min) caused significant decreases in feeding compared to control (sCSF). Desulfated CCK-OP had no effect on feeding at a dose (0.638 pmoles/min) that causes 80–100% decreases in feeding when the C-7 tyrosine is sulfated. Feed intake was significantly less with 2.55 pmoles/min CCK-OP than with an equal dose of desulfated CCK-OP. These results concur with those of previous studies on specific CCK receptors in the pancreas and in the brain, and therefore support the concept of specific CCK receptors in brain having a role in satiety.