Cholecystokinin-33, but not cholecystokinin-8 shows gastrointestinal site specificity in regulating feeding behaviors in male rats

Abstract

Two separate experiments were performed to localize the gastrointestinal sites of action regulating meal size (MS), intermeal interval (IMI) length and satiety ratio (SR, IMI/MS) by cholecystokinin (CCK) 8 and 33. Experiment 1: CCK-8 (0, 0.05, 0.15, 0.25 nmol/kg) was infused in the celiac artery (CA, supplies stomach and upper duodenum) or the cranial mesenteric artery (CMA, supplies small and part of the large intestine) prior to the onset of the dark cycle in free feeding, male Sprague Dawley rats and MS (normal rat chow), IMI and SR were recorded. Experiment 2: CCK-33 (0, 0.05, 0.15, 0.25 nmol/kg) were infused in the CA or the CMA, under the same experimental conditions above, and MS, IMI and SR were recorded. Experiment 1 found that CCK-8 reduces MS, prolongs the IMI and increases the SR at sites supplied by both arteries. Experiment 2 found that CCK-33 reduces MS and increases the SR at sites supplied by the CMA. We conclude that in male rats the feeding behaviors evoked by CCK-33, but not CCK-8, are regulated at specific gastrointestinal sites of action.

Non-sulfated cholecystokinin-8 reduces meal size and prolongs the intermeal interval in male Sprague Dawley rats

“…Further studies are required to determine the specific peripheral site of action that regulates reduction of food intake by NS CCK-8. For example, through intra-arterial infusions of various gut satiety peptides our laboratory demonstrated that the gastrointestinal tract contains sites of action regulating food intake reduction by S CCK-8, sulfated CCK-58, glucagon like peptide-1 and gastrin releasing peptide-29 (Sayegh et al, 2015;Williams et al, 2016;Washington et al, 2016;Washington et al, 2014). Similar experiments are needed to demonstrate a peripheral site of action regulating reduction of food intake by NS CCK-8.…”

Role of the gut–brain axis in energy and glucose metabolism

“…For example, while CCK-8, the most abundantly utilized form, reduced meal size when given exogenously (at various nmol/kg doses), CCK-58, the major endocrine form in rats and humans, reduced meal size and increased the interval time between meals 161 . Furthermore, the effects of the various forms of CCK, namely, CCK-8, 33, and 58, differ depending on their site of action in the gastrointestinal tract [162][163][164] . However, in studies, the most frequently administered exogenous form is CCK-8 165 , despite it not being the major endocrine form.…”