AIM: To study the interactive relationship of gallbladder motor function, plasma cholecystokinin (CCK) and cholecystokinin A receptor (CCK-R) of gallbladder in patients with cholesterol stone disease.METHODS: Gallblad...AIM: To study the interactive relationship of gallbladder motor function, plasma cholecystokinin (CCK) and cholecystokinin A receptor (CCK-R) of gallbladder in patients with cholesterol stone disease.METHODS: Gallbladder motility was studied by ultrasonography in 33 patients with gallbladder stone and 10 health subjects as controls. Plasma CCK concentration was measured by radioimmunoassay in fasting status (CCK-f) and in 30 min after lipid test meal (CCK-30).Radioligand method was employed to analyze the amount and activity of CCK-R from 33 gallstone patients having cholecystectomy and 8 persons without gallstone died of severe trauma as controls.RESULTS: The percentage of cholesterol in the gallstone composition was more than 70%. The cholesterol stone type was indicated for the patients with gallbladder stone in this study. Based on the criterion of gallbladder residual fraction of the control group, 33 gallstone patients were divided into two subgroups, contractor group (14 cases)and non-contractor group (19 cases), The concentration of CCK-30 was significantly higher in non-contractor group than that in both contractor group and control group (55.86±3.86 pmol/l vs 37.85±0.88 pmol/l and 37.95±0.74 pmol/L, P＜0.01), but there was no difference between contractor group and control group. Meanwhile no significant difference of the concentration of CCK-f could be observed among three groups. The amount of CCK-R was lower in non-contractor group than those in both control group and contractor group (10.27±0.94 fmol/mg vs24.59±2.39 fmol/mg and 22.66±0.55 fmol/mg, P＜0.01).The activity of CCK-R shown as KD in non-contractor group decreased compared to that in control group and contractor group. Only was the activity of CCK-R lower in contractor group than that in control group. The ejection fraction correlated closely with the amount of CCK-R (r = 0.9683,P＜0.01), and the concentration of CCK-30 correlated negatively with the amount of CCK-R closely (r = -0.9627,P＜0.01).CONCLUSION: The distinctive interactive relationship of gallbladder emptying, plasma CCK and CCK-R in gallbladder from this study suggested that the defect of CCK-R may be a key point leading to the impairment of gallbladder motor function and the pathogenesis of cholesterol gallstoneformation may differ in two subgroups of gallstone patient,gallbladder non-contractor group or contractor group.展开更多
Objective： To investigate the effect of Chaiqin Chengqi Decoction （柴芩承气汤,CQCQD） on cholecystokinin receptor 1 （CCKR1）-mediated signal transduction of pancreatic acinar cell in rats with acute necrotic pancre...Objective： To investigate the effect of Chaiqin Chengqi Decoction （柴芩承气汤,CQCQD） on cholecystokinin receptor 1 （CCKR1）-mediated signal transduction of pancreatic acinar cell in rats with acute necrotic pancreatitis （ANP）. Methods： Twenty-seven Sprague-Dawley rats were randomized into three groups： the control group, the ANP group, and the CQCQD group （9 in each group）. ANP rats were induced by two intraperitoneal injections of 8% L-arginine （pH=7.0, 4.4 g/kg） over a 2-h period. Rats were treated with 1.5 mL/100 g body weight of CQCQD （CQCQD group） or physiological saline （control and ANP groups） at 2 h interval. And 6 h after induction, pancreatic tissues were collected for histopathological examination. Pancreatic acinar cells were isolated for determination of CCKR1 mRNA and protein expression, phospholipase C （PLC） and inositol-1,4,5-triphosphate （IP3）, and determination of fluorescence intensity （FI） as a measure of intracellular calcium ion concentration [Ca2＋]i. Results： The pancreatic histopathological score （6.2± 1.1） and the levels of PLC （1,187.2±228.2μg/mL） and IP3 （872.2±88.4 μg/mL） of acinar cells in the ANP group were higher than those in the control （2.8± 0.4, 682.5± 121.8 μ g/mL, 518.4 ± 115.8 μ g/mL） and the CQCQD （3.8± 0.8, 905.3± 78.5 μ g/mL, 611.0±42.5μ g/mL） groups （P〈0.05）. [Ca2＋]i FI for the ANP group （34.8± 27.0） was higher than that in the control （5.1 ± 2.2） and CQCQD （12.6± 2.5） groups （P〈0.05）. The expression of pancreatic acinar cell CCKR1 mRNA in the ANP group was up-regulated （expression ratio=1.761; ,0=0.024） compared with the control group. The expression of pancreatic acinar cell CCKR1 mRNA in the CQCQD group was down-regulated （expression ratio=0.311; P=0.035） compared with the ANP group. The ratio of gray values of the CCKR1 and β-actin in the ANP group （1.43±0.17） was higher than those in the control （0.70 ± 0.15） and CQCQD （0.79± 0.11） groups （P〈0.05）. Conclusions： Pancreatic acinar ceil calcium overload of ANP induced by L-arginine was related to the up-regulated expressions of pancreatic acinar cell CCKR1 mRNA and protein. CQCQD can down-regulate expressions of pancreatic acinar cell CCKR1 mRNA and protein to reduce the PLC and IP3 of pancreatic acinar cells, relieving the calcium overload and reducing the pathological changes in rats with ANP.展开更多
BACKGROUND:Regulatory peptide receptors have attracted the interest of oncologists as a new promising approach for cancer pathology,imaging and therapy.Although cholecystokinin (CCK) is a potent modulator of gallbladd...BACKGROUND:Regulatory peptide receptors have attracted the interest of oncologists as a new promising approach for cancer pathology,imaging and therapy.Although cholecystokinin (CCK) is a potent modulator of gallbladder contractility and plays a potential role in pancreatic carcinogenesis through CCK type-A receptor (CCKAR),its role in gallbladder cancer (GBC) is still unknown and immunohistochemical detection of CCKAR in the gallbladder has not yet been reported.This novel case-control study aimed to investigate the expression profile of CCKAR in GBC and gallstone disease (GSD).METHODS:This study included 162 samples of gallbladder:94 from GBC and 68 from GSD.Expression of CCKAR was analyzed by immunohistochemistry and immunoblotting.The results were statistically correlated with disease history including age,sex,presence of gallstone,stage and differentiation.RESULTS:CCKAR was positive in 30/68 (44.1%) of GSD and 72/94 (76.6%) of GBC samples.Fifty-one of the 72 (70.8%) CCKAR-positive GBC samples showed over-expression.Interestingly,consistent results also appeared in the immunoblotting study.CONCLUSIONS:CCKAR expression was significantly increased in GBC compared to GSD.Moreover,CCKAR expression was associated with the degree of tumor differentiation,i.e.,less expression in poorly-differentiated tumors.Thus,it has future prognostic and therapeutic implications in the management of GBC.展开更多
Gastrin and cyclooxygenase-2(COX-2) playimportant roles in the carcinogenesis and progression ofgastric cancer.However,it remains unknown whether the combination of cholecystokinin-2(CCK-2) receptor antagonist plus CO...Gastrin and cyclooxygenase-2(COX-2) playimportant roles in the carcinogenesis and progression ofgastric cancer.However,it remains unknown whether the combination of cholecystokinin-2(CCK-2) receptor antagonist plus COX-2 inhibitor exerts synergistic anti-tumor effects on human gastric cancer.Here,we demonstrated that the combination of AG-041R(a CCK-2 receptor antagonist) plus NS-398(a selective COX-2 inhibitor) treatment had synergistic effects on proliferation inhibition,apoptosis induction,down-regulation of Bcl-2 and up-regulation of Bax expression in MKN-45 cells.These results indicate that simultaneous targeting of CCK-2 receptor and COX-2 may inhibit gastric cancer development more effectively than targeting either molecule alone.(C)2008 Elsevier Ireland Ltd.All rights reserved.展开更多
Objective:To investigate the effects of CCK-8 receptor on lung injury in endotoxemia rats. Methods: Male SD rats were randomized into four groups (n=6): control group (LPS+CCK-8 group), CCK-1R antagonist group, CCK-2R...Objective:To investigate the effects of CCK-8 receptor on lung injury in endotoxemia rats. Methods: Male SD rats were randomized into four groups (n=6): control group (LPS+CCK-8 group), CCK-1R antagonist group, CCK-2R antagonist group, DFSO+PF group. The rats were injected by LPS (5 mg.kg-1). CCK-8 (20 μg.kg-1) was administered 30 min after LPS injection. Either a specific CCK-1R antagonist or CCK-2R antagonist (0.5.kg-1) was injected before CCK-8 treatment (after LPS 20min). The tidal volume (TV) was collected by a multi-channel data physiological recorder. The lung injury was observed by light and electron microscopy. The concentrations of TNF-α、IL-1 and IL-6 in lung homogenates were measured by ELISA kits.Rresults: Compared with control group, the TV were significantly lower and the lung injuries were more serious in CCK-2R antagonist group. As well as the concentrations of TNF-α、IL-1 and IL-6 in lung homogenates were higher.Conclusion: CCK-2 receptor plays a major role in the effect of CCK-8 on lung injury in ETM rats.展开更多
Gastrin(gas)is a peptide hormone that stimulates gastric acid secretion by gastric parietal cells and stimulates gastric motility.The cholecystokinin B receptor(cckbr)can act as a receptor for gastrin,conveying regula...Gastrin(gas)is a peptide hormone that stimulates gastric acid secretion by gastric parietal cells and stimulates gastric motility.The cholecystokinin B receptor(cckbr)can act as a receptor for gastrin,conveying regulatory information on gastrin,but there are fewer studies on its function in fish.The Lateolabrax maculatus is one of the marine aquaculture species in China,it widely distribute in coastal areas.In the study,we cloned the genes of Lateolabrax maculatus gastrin(Lm-gas)and Lateolabrax maculatus cholecystokinin B receptor(Lm-cckbr).The results showed that the full-length gene of Lm-gas is 638bp and the carboxy-terminal conserved domain(DFGRR)is the core functional domain of gastrin protein.The Lm-cckbr gene has a total nucleotide sequence of 2066 bp,and the open reading frame encodes a total of 453 amino acids.The result of protein sequence alignment showed that the similarity between Lm-cckbr protein and other different species was 50.11%-89.67%.The PCR results showed that Lm-gas and Lm-cckbr were expressed in brain and stomach.Further localization by immunehistochemical staining showed that Lm-gas protein was located in the mucosal layer of the gastric wall,but the expression signal was weak in the brain.Hunger causeed a significant decrease in these two genes.The results provided basic research data for further study on the function of Lm-gas and its recepter Lm-cckbr in the in the central nervous system and digestive system of Lateolabrax maculatus.展开更多
基金Supported by the Science Development Foundation of Shanghai,No. 95411902
文摘AIM: To study the interactive relationship of gallbladder motor function, plasma cholecystokinin (CCK) and cholecystokinin A receptor (CCK-R) of gallbladder in patients with cholesterol stone disease.METHODS: Gallbladder motility was studied by ultrasonography in 33 patients with gallbladder stone and 10 health subjects as controls. Plasma CCK concentration was measured by radioimmunoassay in fasting status (CCK-f) and in 30 min after lipid test meal (CCK-30).Radioligand method was employed to analyze the amount and activity of CCK-R from 33 gallstone patients having cholecystectomy and 8 persons without gallstone died of severe trauma as controls.RESULTS: The percentage of cholesterol in the gallstone composition was more than 70%. The cholesterol stone type was indicated for the patients with gallbladder stone in this study. Based on the criterion of gallbladder residual fraction of the control group, 33 gallstone patients were divided into two subgroups, contractor group (14 cases)and non-contractor group (19 cases), The concentration of CCK-30 was significantly higher in non-contractor group than that in both contractor group and control group (55.86±3.86 pmol/l vs 37.85±0.88 pmol/l and 37.95±0.74 pmol/L, P＜0.01), but there was no difference between contractor group and control group. Meanwhile no significant difference of the concentration of CCK-f could be observed among three groups. The amount of CCK-R was lower in non-contractor group than those in both control group and contractor group (10.27±0.94 fmol/mg vs24.59±2.39 fmol/mg and 22.66±0.55 fmol/mg, P＜0.01).The activity of CCK-R shown as KD in non-contractor group decreased compared to that in control group and contractor group. Only was the activity of CCK-R lower in contractor group than that in control group. The ejection fraction correlated closely with the amount of CCK-R (r = 0.9683,P＜0.01), and the concentration of CCK-30 correlated negatively with the amount of CCK-R closely (r = -0.9627,P＜0.01).CONCLUSION: The distinctive interactive relationship of gallbladder emptying, plasma CCK and CCK-R in gallbladder from this study suggested that the defect of CCK-R may be a key point leading to the impairment of gallbladder motor function and the pathogenesis of cholesterol gallstoneformation may differ in two subgroups of gallstone patient,gallbladder non-contractor group or contractor group.
基金Supported by Government Foundation Grant from Hebei Provincial Department of Education,No.HBGX2005-52and National Natural Science Foundation of China,No.30371413
文摘AIM: To compare the binding of cholecystokinin (CCK)-8 to CCK receptors in sling and clasp fibers of the human lower esophageal sphincter.
基金Supported by the National Natural Science Foundation of China(No.81072910)the Science and Technology Supported Program of Sichuan Province,China(No.2010SZ0068 and 2011SZ0291)
文摘Objective： To investigate the effect of Chaiqin Chengqi Decoction （柴芩承气汤,CQCQD） on cholecystokinin receptor 1 （CCKR1）-mediated signal transduction of pancreatic acinar cell in rats with acute necrotic pancreatitis （ANP）. Methods： Twenty-seven Sprague-Dawley rats were randomized into three groups： the control group, the ANP group, and the CQCQD group （9 in each group）. ANP rats were induced by two intraperitoneal injections of 8% L-arginine （pH=7.0, 4.4 g/kg） over a 2-h period. Rats were treated with 1.5 mL/100 g body weight of CQCQD （CQCQD group） or physiological saline （control and ANP groups） at 2 h interval. And 6 h after induction, pancreatic tissues were collected for histopathological examination. Pancreatic acinar cells were isolated for determination of CCKR1 mRNA and protein expression, phospholipase C （PLC） and inositol-1,4,5-triphosphate （IP3）, and determination of fluorescence intensity （FI） as a measure of intracellular calcium ion concentration [Ca2＋]i. Results： The pancreatic histopathological score （6.2± 1.1） and the levels of PLC （1,187.2±228.2μg/mL） and IP3 （872.2±88.4 μg/mL） of acinar cells in the ANP group were higher than those in the control （2.8± 0.4, 682.5± 121.8 μ g/mL, 518.4 ± 115.8 μ g/mL） and the CQCQD （3.8± 0.8, 905.3± 78.5 μ g/mL, 611.0±42.5μ g/mL） groups （P〈0.05）. [Ca2＋]i FI for the ANP group （34.8± 27.0） was higher than that in the control （5.1 ± 2.2） and CQCQD （12.6± 2.5） groups （P〈0.05）. The expression of pancreatic acinar cell CCKR1 mRNA in the ANP group was up-regulated （expression ratio=1.761; ,0=0.024） compared with the control group. The expression of pancreatic acinar cell CCKR1 mRNA in the CQCQD group was down-regulated （expression ratio=0.311; P=0.035） compared with the ANP group. The ratio of gray values of the CCKR1 and β-actin in the ANP group （1.43±0.17） was higher than those in the control （0.70 ± 0.15） and CQCQD （0.79± 0.11） groups （P〈0.05）. Conclusions： Pancreatic acinar ceil calcium overload of ANP induced by L-arginine was related to the up-regulated expressions of pancreatic acinar cell CCKR1 mRNA and protein. CQCQD can down-regulate expressions of pancreatic acinar cell CCKR1 mRNA and protein to reduce the PLC and IP3 of pancreatic acinar cells, relieving the calcium overload and reducing the pathological changes in rats with ANP.
基金supported by a grant from the Indian Council of Medical Research(ICMR Project Ref No.3/2/2/187/2009/NCD-Ⅲ)
文摘BACKGROUND:Regulatory peptide receptors have attracted the interest of oncologists as a new promising approach for cancer pathology,imaging and therapy.Although cholecystokinin (CCK) is a potent modulator of gallbladder contractility and plays a potential role in pancreatic carcinogenesis through CCK type-A receptor (CCKAR),its role in gallbladder cancer (GBC) is still unknown and immunohistochemical detection of CCKAR in the gallbladder has not yet been reported.This novel case-control study aimed to investigate the expression profile of CCKAR in GBC and gallstone disease (GSD).METHODS:This study included 162 samples of gallbladder:94 from GBC and 68 from GSD.Expression of CCKAR was analyzed by immunohistochemistry and immunoblotting.The results were statistically correlated with disease history including age,sex,presence of gallstone,stage and differentiation.RESULTS:CCKAR was positive in 30/68 (44.1%) of GSD and 72/94 (76.6%) of GBC samples.Fifty-one of the 72 (70.8%) CCKAR-positive GBC samples showed over-expression.Interestingly,consistent results also appeared in the immunoblotting study.CONCLUSIONS:CCKAR expression was significantly increased in GBC compared to GSD.Moreover,CCKAR expression was associated with the degree of tumor differentiation,i.e.,less expression in poorly-differentiated tumors.Thus,it has future prognostic and therapeutic implications in the management of GBC.
文摘Gastrin and cyclooxygenase-2(COX-2) playimportant roles in the carcinogenesis and progression ofgastric cancer.However,it remains unknown whether the combination of cholecystokinin-2(CCK-2) receptor antagonist plus COX-2 inhibitor exerts synergistic anti-tumor effects on human gastric cancer.Here,we demonstrated that the combination of AG-041R(a CCK-2 receptor antagonist) plus NS-398(a selective COX-2 inhibitor) treatment had synergistic effects on proliferation inhibition,apoptosis induction,down-regulation of Bcl-2 and up-regulation of Bax expression in MKN-45 cells.These results indicate that simultaneous targeting of CCK-2 receptor and COX-2 may inhibit gastric cancer development more effectively than targeting either molecule alone.(C)2008 Elsevier Ireland Ltd.All rights reserved.
基金Research Project of Hebei Administration of Traditional Chinese Medicine(2017005)Youth Fund of Hebei University of Chinese Medicine(QNZ2014036)
文摘Objective:To investigate the effects of CCK-8 receptor on lung injury in endotoxemia rats. Methods: Male SD rats were randomized into four groups (n=6): control group (LPS+CCK-8 group), CCK-1R antagonist group, CCK-2R antagonist group, DFSO+PF group. The rats were injected by LPS (5 mg.kg-1). CCK-8 (20 μg.kg-1) was administered 30 min after LPS injection. Either a specific CCK-1R antagonist or CCK-2R antagonist (0.5.kg-1) was injected before CCK-8 treatment (after LPS 20min). The tidal volume (TV) was collected by a multi-channel data physiological recorder. The lung injury was observed by light and electron microscopy. The concentrations of TNF-α、IL-1 and IL-6 in lung homogenates were measured by ELISA kits.Rresults: Compared with control group, the TV were significantly lower and the lung injuries were more serious in CCK-2R antagonist group. As well as the concentrations of TNF-α、IL-1 and IL-6 in lung homogenates were higher.Conclusion: CCK-2 receptor plays a major role in the effect of CCK-8 on lung injury in ETM rats.
基金This project was supported by the National Key Research and Development Program of China(2017YFC0506003)Blue Granary Science and Technology Innovation Project,and Shanghai Collaborative Innovation Center of Animal Genetics and Breeding(ZF1206).
文摘Gastrin(gas)is a peptide hormone that stimulates gastric acid secretion by gastric parietal cells and stimulates gastric motility.The cholecystokinin B receptor(cckbr)can act as a receptor for gastrin,conveying regulatory information on gastrin,but there are fewer studies on its function in fish.The Lateolabrax maculatus is one of the marine aquaculture species in China,it widely distribute in coastal areas.In the study,we cloned the genes of Lateolabrax maculatus gastrin(Lm-gas)and Lateolabrax maculatus cholecystokinin B receptor(Lm-cckbr).The results showed that the full-length gene of Lm-gas is 638bp and the carboxy-terminal conserved domain(DFGRR)is the core functional domain of gastrin protein.The Lm-cckbr gene has a total nucleotide sequence of 2066 bp,and the open reading frame encodes a total of 453 amino acids.The result of protein sequence alignment showed that the similarity between Lm-cckbr protein and other different species was 50.11%-89.67%.The PCR results showed that Lm-gas and Lm-cckbr were expressed in brain and stomach.Further localization by immunehistochemical staining showed that Lm-gas protein was located in the mucosal layer of the gastric wall,but the expression signal was weak in the brain.Hunger causeed a significant decrease in these two genes.The results provided basic research data for further study on the function of Lm-gas and its recepter Lm-cckbr in the in the central nervous system and digestive system of Lateolabrax maculatus.
