No abstract available.
Cholecystokinin ; Colon

BACKGROUND/AIMS: At present, the gallbladder dysfunction implies a disorder of decreased gallbladder contractility. Other motor disorder such as overactive gallbladder which shows excessive contraction cannot be excluded in the motility disorder of gallbladder. Thus, this study was done to define the diagnostic criteria and to develop the techniques to induce the excessive contraction of gallbladder. METHODS: CCK-op at 20 ng/kg by slow continuous infusion for 30minutes, that is known as most physiologic method for gallbladder contraction, was given for assessment of gallbladder emptying in 12 normal volunteers. Also, rapid bolus injection of cholecystokinin octapeptide (CCK-op) at 20 ng/kg or 40 ng/kg was performed to induce the excessive contraction of gallbladder. Gallbladder contractility was represented as the ejection fraction (GBEF) measured by cholecystokinin-cholescintigraphy. RESULTS: 1. With a slow continuous infusion of CCK-op, the mean GBEF was 78.2+/-5.6% (mean+/-SD). 2. With a rapid bolus injection of CCK-op, GBEF showed variable results (10-86%) among subjects who had normal gallbladder. 3. Based on the results obtained by slow continuous infusion of CCK-op in normal volunteers, overactive gallbladder was defined when GBEF approached more than 70% within 15minutes after bolus injection of CCK-op. The overactive gallbladder was noted in 6 (50%) subjects who received rapid bolus injection of CCK-op (40 ng/kg). 4. Abdominal pain developed only in high-dose (40 ng/kg) bolus injection group (6/12, 50%), concomitantly with increased bowel movements, irrespective of excessive gallbladder contractility. CONCLUSION: Excessive gallbladder contraction had no clinical significance in the experimentally induced clinical model.
Abdominal Pain ; Cholecystokinin ; Gallbladder Emptying ; Gallbladder* ; Healthy Volunteers ; Sincalide

PURPOSE: Gastrin and cholecystokinin (CCK) have been reported to play a role in the development and growth stimulation of gastrointestinal cancers including pancreatic cancer. METHODS: We investigated the effects of gastrin and CCK on the growth of pancreatic and biliary tract cancer cell lines established at the Cancer Research Institute of Seoul National University College of Medicine, using reverse transcription-polymerase chain reaction (RT-PCR) and slot blot hybridization, to examine the expressions of hormonal receptors in these cell lines. RESULTS: Of the six biliary tract, and five pancreatic, cancer cell lines, SNU-308 showed a growth stimulated effect due to gastrin-17, as did SNU-478 to both gastrin-17 and CCK-8. The trophic effect of these two hormones was completely blocked by specific antagonists (L-365, 260 for gastrin and L-364, 718 for CCK). The other cell lines did not respond to either the gastrin or the CCK. From the RT-PCR, the presence of the CCK-A receptor and the CCK-B/gastrin receptor mRNA was detected in all the biliary and pancreatic cancer cell lines. From the slot blot hybridization, although the cell lines that responded to the hormones showed high level of expression for receptor mRNA, so did some of those not responding to the hormones. CONCLUSION: This study suggests that gastrin and CCK exert a trophic action on some biliary tract cancers due to their specific receptors. However, further studies investigating the functional and structural variation among these receptors, in relation to their subtypes and mutation/polymorphism are requisite prior to their clinical usage for adjunctive hormonal or antihormonal therapy can be recommended.
Academies and Institutes ; Bile Duct Neoplasms ; Biliary Tract ; Biliary Tract Neoplasms ; Cell Line* ; Cholecystokinin* ; Gallbladder Neoplasms ; Gastrins* ; Gastrointestinal Neoplasms ; Growth and Development ; Pancreatic Neoplasms ; Receptor, Cholecystokinin A ; RNA, Messenger ; Seoul ; Sincalide

Cholecystokinin (CCK) is a gastrointestinal hormone which plays an important role in satiety and gastric motility. It is also widely distributed throughout the central nervous system, where it appears to be involved in the central control of anxiety, feeding behavior and nociception. Two distinct CCK receptor types, CCKA and CCKB, have been found in the brain. Both CCK receptors coexist in the rat nucleus tractus solitarius (NTS), which is the primary center for the coordination of peripheral and central activities related to gastrointestinal, cardiovascular and respiratory functions. In order to study ionic actions of CCK on each type of receptor, we investigated the effects of CCK-8S on neurons located in the NTS of the rat using whole-cell patch-clamp recordings in brainstem slices. Application of CCK-8S, under current clamp, produced a membrane depolarization accompanied by action potential firing. This CCK-evoked excitation was dose-dependent (10 nM ~ 10 micrometer) and observed in more than 60% of NTS neurons. Under voltage clamp conditions, CCK-8S induced an inward current with a notably increased spontaneous excitatory synaptic activity. However, CCK-8S did not significantly change the amplitude of pharmacologically isolated and evoked EPSP(C)s. Using selective CCKA and CCKB receptor antagonists, we observed two different effects of CCK-8S, which suggest CCKA receptor-mediated inhibitory and CCKB receptor-mediated excitatory effects in the NTS. These results may help to explain the ability of CCK to modulate gastrointestinal and other reflex systems in the NTS.
Action Potentials ; Animals ; Anxiety ; Brain ; Brain Stem ; Central Nervous System ; Cholecystokinin* ; Feeding Behavior ; Fires ; Membranes ; Neurons* ; Nociception ; Rats* ; Receptors, Cholecystokinin ; Reflex ; Sincalide* ; Solitary Nucleus*

BACKGROUND/AIMS: It 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. METHODS: An 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. RESULTS: Exogenous 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. CONCLUSIONS: CCK 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.
Animals ; Atropine ; Catheters ; Cholecystokinin ; Colon ; Peptide YY ; Phenobarbital ; Proglumide ; Rats ; Sincalide ; Transducers, Pressure

No abstract available.
Cholecystokinin* ; Gallbladder Emptying* ; Gallbladder* ; Meals*

Capsaicin, a pungent ingredient of hot pepper, elicits an intense burning pain when applied cutaneously and intradermally. Activation of capsaicin-gated channel in. C-type dorsal root ganglion (DRG) neurons produces nonselective cationic currents. Although electrophysiological and biochemical properties of capsaicin-activated current (ICAP) were studied, the regulatory mechanism and intracellular signaling pathway are still unclear. In the present study, we investigated the modulations of ICAP by DAMGO (micro-opioid agonist) and cholecystokinin octapeptide (CCK-8). In 18 out of 86 cells, the amplitude of ICAP was significantly increased by DAMGO and completely reversed after washout, while ICAP was decreased by DAMGO in 25 cells. In 43 cells, DAMGO had no effect on ICAP. Mean action potential duration was significantly different between 'increased-by-DAMGO' group and 'decreased-by-DAMGO' group. Mean amplitudes of IH were not significantly different between both groups. CCK-8 reversibly enhanced the amplitude of ICAP (5/13). DAMGO also increased ICAP amplitude significantly in the same cells. The amplitude of ICAP was increased in additive manner by combined applications of DAMGO and CCK-8 in these cells. These results suggest that DAMGO and CCK-8 can either increase or decrease ICAP presumably depending on the subtypes of DRG cells and classified by electrophysiological properties.
Action Potentials ; Analgesics, Opioid ; Animals ; Burns ; Capsaicin ; Cholecystokinin ; Diagnosis-Related Groups ; Enkephalin, Ala(2)-MePhe(4)-Gly(5)-* ; Ganglia, Spinal* ; Neurons ; Rats* ; Sincalide ; Spinal Nerve Roots*

Fenofibrate is a selective peroxisome proliferator-activated receptor alpha (PPARalpha) activator and is prescribed to treat hyperlipidemia. The mechanism through which PPARalpha agonists reduce food intake, body weight, and adiposity remains unclear. One explanation for the reduction of food intake is that fenofibrate promotes fatty acid oxidation and increases the production of ketone bodies upon a standard experimental dose of the drug (100~300 mg/kg/day). We observed that low-dose treatment of fenofibrate (30 mg/kg/day), which does not cause significant changes in ketone body synthesis, reduced food intake in Long-Evans Tokushima (LETO) rats. LETO rats are the physiologically normal controls for Otsuka Long-Evans Tokushima Fatty (OLETF) rats, which are obese and cholecystokinin (CCK)-A receptor deficient. We hypothesized that the reduced food intake by fenofibrate-treated LETO rats may be associated with CCK production. To investigate the anorexic effects of fenofibrate in vivo and to determine whether CCK production may be involved, we examined the amount of food intake and CCK production. Fenofibrate-treated OLETF rats did not significantly change their food intake while LETO rats decreased their food intake. Treatment of fenofibrate increased CCK synthesis in the duodenal epithelial cells of both LETO and OLETF rats. The absence of a change in the food intake of OLETF rats, despite the increase in CCK production, may be explained by the absence of CCK-A receptors. Contrary to the OLETF rats, LETO rats, which have normal CCK receptors, presented a decrease in food intake and an increase in CCK production. These results suggest that reduced food intake by fenofibrate treatment may be associated with CCK production.
Adiposity ; Animals ; Body Weight ; Cholecystokinin ; Diethylpropion ; Eating ; Epithelial Cells ; Fenofibrate ; Hyperlipidemias ; Ketone Bodies ; PPAR alpha ; Rats ; Rats, Inbred OLETF ; Receptor, Cholecystokinin A ; Receptors, Cholecystokinin

Hesperetin (3',5,7-trihydroxy 4'-methoxyflavanone) and its glycoside hesperidin (hesperetin 7-rhamnoglucoside) in oranges have been reported to possess pharmacological effects related to anti-obesity. However, hesperetin and hesperidin have not been studied on suppressive effects on appetite. This study examined that hesperetin and hesperidin can stimulate the release of cholecystokinin (CCK), one of appetite-regulating hormones, from the enteroendocrine STC-1 cells, and then examined the mechanisms involved in the CCK release. Hesperetin significantly and dose-dependently stimulated CCK secretion with an EC50 of 0.050 mM and increased the intracellular Ca2+ concentrations ([Ca2+]i) compared to the untreated control. The stimulatory effect by hesperetin was mediated via the entry of extracellular Ca2+ and the activation of TRP channels including TRPA1. These results suggest that hesperetin can be a candidate biomolecule for the suppression of appetite and eventually for the therapeutics of obesity.
Appetite ; Cholecystokinin* ; Citrus sinensis ; Enteroendocrine Cells ; Hesperidin ; Obesity

BACKGROUND/OBJECTIVES: Cholecystokinin (CCK), a hormone or neuropeptide, is secreted in response to intraluminal nutrients by enteroendocrine I-cells of the intestine and has important physiological actions related to appetite regulation and satiety. The stimulation on CCK secretion from the intestine is of potential relevance for body weight management. Naringenin (4',5,7-trihydroxyflavanone) and its glycoside naringin (naringenin 7-rhamnoglucoside) have been reported to have many biological functions. In the current study, we investigated the question of whether naringenin and naringin could stimulate CCK secretion and then examined the mechanisms involved in CCK release. MATERIALS/METHODS: STC-1 cells were used as a model of enteroendocrine cells. CCK release and changes in intracellular Ca2+ ([Ca2+]i) were measured after incubation of cells with naringenin and naringin for 1 h. RESULTS: Naringenin caused significant (P < 0.05) stimulation of CCK secretion, but naringin did not. In addition, regarding the secretory mechanisms, naringenin-induced CCK secretion involved increases in [Ca2+]i, influx of extracellular Ca2+, at least in part, and activation of TRP channels, including TRPA1. CONCLUSION: Findings of this study suggest that naringenin could have a role in appetite regulation and satiety.
Appetite ; Appetite Regulation ; Body Weight ; Cholecystokinin* ; Enteroendocrine Cells ; Intestines ; Neuropeptides