1.Reduction of Food Intake by Fenofibrate is Associated with Cholecystokinin Release in Long-Evans Tokushima Rats.
Mi Kyoung PARK ; Ying HAN ; Mi Sun KIM ; Eunhui SEO ; Soojeong KANG ; So Young PARK ; Hyeongjong KOH ; Duk Kyu KIM ; Hye Jeong LEE
The Korean Journal of Physiology and Pharmacology 2012;16(3):181-186
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
2.Vagal Control of Satiety and Hormonal Regulation of Appetite.
Chung OWYANG ; Andrea HELDSINGER
Journal of Neurogastroenterology and Motility 2011;17(4):338-348
The paradigm for the control of feeding behavior has changed significantly. In this review, we present evidence that the separation of function in which cholecystokinin (CCK) controls short-term food intake and leptin regulate long-term eating behavior and body weight become less clear. In addition to the hypothalamus, the vagus nerve is critically involved in the control of feeding by transmitting signals arising from the upper gut to the nucleus of the solitary tract. Among the peripheral mediators, CCK is the key peptide involved in generating the satiety signal via the vagus. Leptin receptors have also been identified in the vagus nerve. Studies in the rodents clearly indicate that leptin and CCK interact synergistically to induce short-term inhibition of food intake and long-term reduction of body weight. The synergistic interaction between vagal CCK-A receptor and leptin is mediated by the phosphorylation of signal transducer and activator of transcription3 (STAT3), which in turn, activates closure of K+ channels, leading to membrane depolarization and neuronal firing. This involves the interaction between CCK/SRC/phosphoinositide 3-kinase cascades and leptin/Janus kinase-2/phosphoinositide 3-kinase/STAT3 signaling pathways. It is conceivable that malfunctioning of these signaling molecules may result in eating disorders.
Appetite
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Body Weight
;
Cholecystokinin
;
Eating
;
Feeding and Eating Disorders
;
Feeding Behavior
;
Fires
;
Hypothalamus
;
Leptin
;
Membranes
;
Neurons
;
Nodose Ganglion
;
Phosphorylation
;
Receptor, Cholecystokinin A
;
Receptors, Leptin
;
Rodentia
;
Signal Transduction
;
Solitary Nucleus
;
Transducers
;
Vagus Nerve
3.Photodynamic modulation of cellular functions.
Yuan LI ; Hong-Ning JIANG ; Zong-Jie CUI
Acta Physiologica Sinica 2016;68(4):534-546
Photodynamic action, due to the rather limited lifetime (1 μs) and effective reactive distance of singlet oxygen (< 10 nm), could subcellular-specifically regulate different cellular functions. Photodynamic action could activate permanently cholecystokinin (CCK) 1 receptors, and sensitize or desensitize other G protein-coupled receptors. The emergence in recent years of genetically- encoded protein photosensitisers has enabled more precisely-targeted photodynamic modulation of subcellular organelles and functional proteins. Protein photosensitisers (such as KillerRed, miniSOG or SOPP) expressed on the plasma membrane, mitochondria, lysosomes or endoplasmic reticulum can modulate photodynamically subcellular functions and fine-tune protein activity by targeted photooxidation. With the newly emerged active illumination technique, simultaneous photodynamic action localized at multiple sites is now possible, and the contribution of subcellular regions to the whole cell or individual cells to a cell cluster could be quantitated. Photodynamic action with protein photosensitiser will be a powerful tool for nano-manipulation in cell physiology research.
Endoplasmic Reticulum
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Light
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Mitochondria
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Photosensitizing Agents
;
Receptors, Cholecystokinin
4.Association Studies of the CT Repeat Polymorphism in the Cholecystokinin B Receptor Gene with the Diagnosis and the Response of Pharmacotherapy in Korean Patients with Panic Disorder.
Young Hee CHOI ; Jong Min WOO ; Jeong Hoon BAE ; Dae Yeon CHO ; Won KIM
Korean Journal of Psychopharmacology 2006;17(1):60-69
OBJECTIVE: This study aimed to test the possible association between Cholecystokinin B receptor (CCKBR) promoter gene and panic disorder. METHODS: 262 patients with panic disorder and 76 healthy controls participated in this study. Genotyping was performed by polymerase chain reaction-based method. RESULTS: Allele distribution of CT repeat polymorphism in patients with panic disorder was not different from those of the controls. However, after excluding the patients with panic disorder comorbid with major depressive disorder and other anxiety disorder, we found out the significant association of CCKBR (CT)n repeat with the panic disorder without comorbidities. And we analysed the data as a di-allelic polymorphism with a short (140-162 bp) and a long (164-180 bp) allele. In the di-allelic analysis, there was an excess of the shorter allele in patients with panic disorder. CONCLUSION: The present study suggested that the CCKBR promoter dinucleotide polymorphism may have a potential role for susceptibility to panic disorder in the Korean population and thus calls for consecutive studies in order to pile up the data with larger different ethnic background.
Alleles
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Anxiety Disorders
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Cholecystokinin*
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Comorbidity
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Depressive Disorder, Major
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Diagnosis*
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Drug Therapy*
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Humans
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Panic Disorder*
;
Panic*
;
Receptor, Cholecystokinin B*
5.Effects of Poly I:C in inducing growth inhibition and apoptosis of human hepatocellular carcinoma cells.
Peng SHEN ; Ting-Wan JIANG ; Hui-Qi LU ; Ling-Zhen ZHANG ; Huan-Xing HAN ; Rong-Cheng LUO
Journal of Southern Medical University 2009;29(3):525-527
<b>OBJECTIVEb>To explore the effect and mechanism of Poly I:C in inducing growth inhibition and apoptosis of human hepatocellular carcinoma SMMC-7721 cells.
<b>METHODSb>SMMC-7721 cells were treated with different doses of Poly I:C for 24, 48, and 72 h, and the cell growth inhibition rate was analyzed with CCK-8 assay. The cell cycle and the apoptosis were analyzed using flow cytometry with Annexin-V and PI staining, and quantitative RT-PCR analysis were used to detect the expression of TLR3, TRIF, and IFN-beta mRNA in cells.
<b>RESULTSb>In the cells exposed to Poly I:C at low, moderate, and high doses, the inhibitory rates was the highest in high-dose Poly I:C group, and at a given Poly I:C dose, prolonged exposure resulted in significantly increased cell growth inhibition rate (P<0.05). Flow cytometry showed that Poly I:C induced cell apoptosis in a time- and dose-dependent manner and significantly increased the percentage of G1-phase cells as compared with that in the control group. The mRNA level of TLR3, TRIF, and IFN-beta were also increased following Poly I:C treatment in comparison with the control group.
<b>CONCLUSIONb>Poly I:C can induce significant growth inhibition and apoptosis of SMMC-7721 cells in a dose- and time-dependent manner possibly by causing cell cycle arrest and TLR3 signaling pathway activation that leads to IFN-beta production and cell apoptosis.
Apoptosis ; drug effects ; Carcinoma, Hepatocellular ; pathology ; Cell Line, Tumor ; Cell Proliferation ; drug effects ; Dose-Response Relationship, Drug ; Humans ; Interferon-beta ; genetics ; metabolism ; Liver Neoplasms ; pathology ; Poly I-C ; pharmacology ; RNA, Messenger ; genetics ; metabolism ; Receptors, Cholecystokinin ; metabolism ; Signal Transduction ; Toll-Like Receptor 3 ; genetics ; metabolism
6.Association of CCK1 Receptor Gene Polymorphisms and Irritable Bowel Syndrome in Korean.
Seon Young PARK ; Jong Sun REW ; Soo Mi LEE ; Ho Seok KI ; Kyong Rok LEE ; Jun Ho CHEO ; Hyung Il KIM ; Du Yeong NOH ; Young Eun JOO ; Hyun Soo KIM ; Sung Kyu CHOI
Journal of Neurogastroenterology and Motility 2010;16(1):71-76
INTRODUCTION: Cholecystokinin (CCK) belongs to a group of endogenous molecules known as brain-gut neuropeptides and functions as a neuropeptide as well as a gut hormone. It remains unclear whether genetic variation of the CCK receptor plays a role in irritable bowel syndrome (IBS). The aim of this study was to determine and compare the allele and genotype frequencies of the CCK1 receptor polymorphisms between healthy controls and patients with IBS. METHODS: Genotyping of 80 patients with IBS (who met the Rome III criteria) and 76 healthy controls was performed. We performed PCR amplification for the CCK1 receptor intron 1 779 T > C and Exon 1 G > A. We confirmed polymorphisms by direct sequencing method. RESULTS: There was a significantly different trend for genotypic distributions of the CCK1 receptor polymorphism between patients with IBS and healthy controls (p for trend = 0.048). The CCK1 receptor intron 1 779 T >C polymorphic type was more common in patients with 'IBS-constipation predominant (IBS-C) and IBS-mixed (IBS-M) forms' (19/31, 61.3%) than healthy controls 32/76, 42.1% adjusted odd ratio 2.43, 95% Confidence interval 1.01-5.86). The genotypic distributions of the CCK1 receptor exon 1 polymorphism were not significantly different between the two groups (p for trend = 0.223). CONCLUSIONS: CCK1 receptor polymorphisms were associated with IBS. In particular, the CCK1 receptor intron 1 779 T > C polymorphic type was associated with 'IBS-C and IBS-M'. Further studies are needed in larger number of patients with an even distribution of IBS subtypes.
Alleles
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Cholecystokinin
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Exons
;
Genetic Variation
;
Genotype
;
Humans
;
Introns
;
Irritable Bowel Syndrome
;
Neuropeptides
;
Polymerase Chain Reaction
;
Receptors, Cholecystokinin
;
Rome
7.The effect of formalin-induced pain on CCK in rat spinal cord neurons.
Li LI ; Hong-an LI ; Jin-fang JIANG ; Wei-hua LIANG ; Jun-qiang SI
Chinese Journal of Applied Physiology 2009;25(2):217-220
<b>AIMb>CCK is one of the strongest endogenous anti-opioid substances and suppresses morphine tolerance which results from long term use of morphine. This study explores the modulatory effect of CCK on pain formalin-induced.
<b>METHODSb>The effect of formalin-induced pain on CCK immunoreactivity in rat sensory neurons was observed through immunohistochemistry technique.
<b>RESULTSb>After 1 h of subcutaneous injection of formalin in one paw of rats, the number of positive neurons of CCK immunoreactivity in spinal cord neurons was obviously increased and greater than that of non-injection side (P <0.01). The semi-quantitative optical density average values of CCK immunoreactivity neurons were 0.397 +/- 0.014 and 0.295 +/- 0.007 in injection side and non-injection side respectively, the difference was obvious (P < 0.01). After 3 h of subcutaneous injection of formalin in one paw of rats, the semi-quantitative optical density average values of CCK immunoreactivity neurons were 0.366 +/- 0.009 and 0.303 +/- 0.005 in injection side and noninjection side respectively, the difference was significant (P < 0.01).
<b>CONCLUSIONb>Formalin-induced pain can significantly change semi-quantitative optical density average value of CCK immunoractivity in spinal cord neurons, this indicates CCK participates in modulation of pain.
Animals ; Cholecystokinin ; metabolism ; physiology ; Female ; Formaldehyde ; Male ; Neurons ; metabolism ; Pain ; chemically induced ; physiopathology ; Random Allocation ; Rats ; Rats, Wistar ; Receptors, Cholecystokinin ; metabolism ; physiology ; Spinal Cord ; metabolism ; pathology
8.Effect of cholesterol in bile on cholecystokinin receptor in the gallbladder.
Huaqun FU ; Weiding WU ; Shubing ZOU ; Mingwen HUANG ; Changwen HUANG ; Yanping XU
Chinese Journal of Surgery 2002;40(10):786-788
<b>OBJECTIVEb>To assess the effect of cholesterol in bile on cholecystokinin receptor (CCK-R) in the gallbladder.
<b>METHODSb>One hundred Guinea pigs were randomly divided into four groups, 25 animals for each. The control group was fed a standard diet, and the cholesterol group fed a diet containing 2% cholesterol. After taking the 2% cholesterol diet for two weeks, the natural group persisted on the standard diet, and the treated group was perfused by traditional Chinese medicine. Serum cholecystokinin (CCK) level in the portal vein and maximal binding capacity (B(max)) and Kd of CCK-R in the gallbladder were measured in the four groups by RIA and RBA, and the concentrations of cholesterol in bile were also observed.
<b>RESULTSb>Compared with the control group, after high-cholesterol feeding for two weeks, the gallbladder emptying rate [(65.83 +/- 7.32)% approximately (47.22 +/- 5.24)%] and B(max) of CCK-R [(60 +/- 27) approximately (32 +/- 13) fmol/mg protein] and in decreased fasting gallbladder volume (FV) [(0.89 +/- 0.26) approximately (1.34 +/- 0.61) cm(3)] and concentration of cholesterol [(0.44 +/- 0.11) approximately (0.60 +/- 0.13) mmol/L] in bile increased, but no change was in the serum CCK level and Kd of CCK-R in the cholesterol group. Compared with the natural group, after two-week in take of herb decoction of qingre lidan and liqi huoxue, FV [(1.27 +/- 0.60) approximately (0.90 +/- 0.27) cm(3)], RV [(0.85 +/- 0.45) approximately (0.32 +/- 0.12) cm(3)], FB [(0.92 +/- 0.35) approximately (0.73 +/- 0.21) cm(3)], RB [(0.76 +/- 0.34) approximately (0.29 +/- 0.08) cm(3)] in the treated group decreased significantly; but gallbladder emptying rate [(43.06 +/- 4.27)% approximately (67.01 +/- 6.82)%] increased significantly. The concentration of cholesterol in bile was lower in the treated group than in the natural group [(0.59 +/- 0.14) approximately (0.43 +/- 0.10) mmol/L], but no change was found in the serum CCK level. Bmax of CCK-R in the treated group increased significantly [(39 +/- 19) approximately (59 +/- 11) fmol/mg protein], Kd of CCK-R showed no significant changes between the treated group and natural group.
<b>CONCLUSIONb>High cholesterol in gallbladder bile causes defective muscle contraction by down-regulating CCK-R in the gallbladder, so the reduction of cholesterol concentration of bile may contribute to gallbladder contraction.
Animals ; Bile ; chemistry ; Cholecystokinin ; blood ; Cholesterol ; analysis ; physiology ; Gallbladder ; chemistry ; physiology ; Guinea Pigs ; In Vitro Techniques ; Male ; Muscle Contraction ; Receptors, Cholecystokinin ; analysis
9.Regulatory effect of clearing-heat secreting-bile regulating-qi flow and activating blood circulation principle on cholecystokinin receptor.
Hua-qun FU ; Wei-ding WU ; Shu-bing ZOU
Chinese Journal of Integrated Traditional and Western Medicine 2003;23(5):367-369
<b>OBJECTIVEb>To explore the regulatory effect of clearing-Heat secreting-bile regulating-Qi flow and activating blood circulation (CSRA) principle on cholecystokinin receptor (CCK-R) and its mechanism.
<b>METHODSb>Cholecystokinin (CCK) in serum of portal venous blood, maximum binding capacity (Bmax) and affinity (Kd) of CCK-R levels in gallbladder of guinea pigs allocated in four groups (control, high cholesterol, natural recovery and treated groups) were determined using radioimmunoassay and radioligand receptor assay (RRA). At the same time, changes of fasting volume (FV) and postprandial volume (PV) of gallbladder, fasting and postprandial bile (FB and PB) in gallbladder, gallbladder contraction rate (GCR) and cholesterol concentration (CC) in bile were observed.
<b>RESULTSb>Compared with the control group, after two weeks of high cholesterol feeding, increase of FV, FB, PV, PB and CC (P < 0.05), and decrease of GCR (P < 0.01) and Bmax were found in cholesterol group, but with no significant change in Kd and CCK level. The above-mentioned criteria were restored to normal range in the treated group.
<b>CONCLUSIONb>CSRA principle could promote the recovery of gallbladder contraction by regulating CCK-R expression in it, its mechanism is possibly correlated with reduction of cholesterol concentration in bile.
Animals ; Bile ; metabolism ; Cholecystokinin ; metabolism ; Cholesterol ; metabolism ; Drugs, Chinese Herbal ; pharmacology ; Gallbladder ; physiopathology ; Guinea Pigs ; Hypercholesterolemia ; metabolism ; Male ; Medicine, Chinese Traditional ; Random Allocation ; Receptors, Cholecystokinin ; metabolism
10.Effects of cholecystokinin octapeptide on neuronal activities in the rat nucleus tractus solitarius.
Hyewhon RHIM ; Chan Woong PARK
The Korean Journal of Physiology and Pharmacology 2000;4(4):275-281
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*