Postponement of Satiety by Blockade of Brain Cholecystokinin (CCK-B) Receptors

TLDR

Exogenous CCK reduces food intake and induces satiety, yet it remains unclear whether endogenous CCK mediates satiety through peripheral CCK‑A or central CCK‑B receptors. The study aims to determine whether endogenous CCK induces satiety via CCK‑A or CCK‑B receptors by employing selective antagonists. Selective antagonists MK‑329 (CCK‑A) and L‑365,260 (CCK‑B) were used to probe satiety mechanisms in partially satiated rats. Blocking CCK‑B receptors with L‑365,260 markedly increased feeding and delayed satiety, whereas blocking CCK‑A had a weaker effect, indicating that endogenous CCK induces satiety through central CCK‑B receptors.

Abstract

Exogenous cholecystokinin (CCK) decreases food intake and causes satiety in animals and man. However, it has not been established that endogenous CCK causes satiety or whether the response is mediated by peripheral-type (CCK-A) or brain-type (CCK-B) receptors. The development of potent and selective antagonists for CCK-A (MK-329) and CCK-B (L-365,260) receptors now allows these issues to be addressed. The CCK-A antagonist MK-329 and the CCK-B antagonist L-365,260 increased food intake in partially satiated rats and postponed the onset of satiety; however, L-365,260 was 100 times more potent than MK-329 in increasing feeding and preventing satiety. These results suggest that endogenous CCK causes satiety by an agonist action on CCK-B receptors in the brain.