Mechanism of Action of Cholecystokinin on Colonic Motility in Isolated, Vascularly Perfused Rat Colon

Abstract

Background/AimsIt is generally believed that cholecystokinin (CCK) stimulates colonic motility, although there are controversial reports. It has also been suggested that postprandial peptide YY (PYY) release is CCK-dependent. Using a totally isolated, vascularly perfused rat colon, we investigated: (1) the roles of CCK and PYY on colonic motility, (2) to determine if CCK modulates PYY release from the colon to influence the motility and (3) to clarify whether the action of CCK and PYY on colonic motility is mediated via the influence of cholinergic input.MethodsAn isolated whole rat colon was used. Luminal pressure was monitored via microtip catheter pressure transducers from proximal and distal colon. After a control period, CCK-8 or PYY was administerd intraarterially with or without an anti-PYY serum, loxiglumide or atropine at 12, 60 and 240 pM. Each dose was given for a period of 15-minute and the contractile response was expressed as % changes over basal. PYY concentration in the portal effluent was determined by radioimmunoassay.ResultsExogenous CCK-8 increased colonic motility which paralleled the increase in PYY release in the portal effluent. Exogenous PYY also significantly increased colonic motility although it was less potent than CCK. The stimulating effect of CCK-8 was significantly inhibited by an anti-PYY serum, and was completely abolished by loxiglumide, and almost completely abolished by atropine.ConclusionsCCK increases colonic motility via CCK1 receptor and it is mediated partly by PYY. Cholinergic input is required for the increased motility by either PYY or CCK.

Bile acids drive colonic secretion of glucagon-like-peptide 1 and peptide-YY in rodents

“…Endocrine routes for distal gut stimulation, including a proximal-distal hormonal loop, have repeatedly gained interest as this would contribute to an explanation of the early postprandial rise in plasma GLP-1 (43,61). Thus, in our hands glucosedependent insulinotropic polypetide (GIP, 1 nM), but not cholecystokinin (CCK, 1 nM), is able to induce GLP-1 and PYY secretion from the isolated perfused rat colon (unpublished data) in agreement with a previous study (48), but in contrast to others (31,49). However, the physiological relevance of high concentrations of duodenal hormones is questionable (24), while the neuropeptide vasoactive intestinal peptide (VIP, 10 nM), stimulating cAMP accumulation in enterocytes, also seems to be without effect on endocrine secretion from the perfused rat colon (unpublished data).…”

Gut‐derived cholecystokinin contributes to visceral hypersensitivity via nerve growth factor‐dependent neurite outgrowth

“…Previous studies have shown that intravenous injection of exogenous CCK increased pain perception and induced rapid colon transit in IBS patients. 18,19 Others reported that intra-arterial injection of exogenous CCK caused an increase of rat colon motility, 25 and administration of exogenous CCK induced contractile responses in isolated colonic smooth muscle cells from normal and highly inflamed human colons. 26 Therefore, although CCK receptor levels were not altered, the increased colonic CCK production may induce enhance pain perception in mouse colorectum.…”

Factors affecting circulating levels of peptide YY in humans: a comprehensive review

“…Circulating levels of PYY are low in the fasted state and both the 3 -36 and 1-36 forms increase rapidly upon nutrient ingestion (14) . While it is well known that PYY is released in response to nutrient intake, it is also released by gastric acid, cholecystokinin (CCK), and infusion of bile acids into the ileum or colon as shown in animal studies (26,27) . Finally, PYY secretion is affected by things other than food consumption such as intestinal peristalsis and intraluminal nutrients (28,29) .…”