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1.
琥珀酰-CCK7为新合成的CCK8的一种类似物,当琥珀酰-CCK7的浓度为1×10^-11mol/L-1×10[-7]mol/L时,能促使大鼠胰腺离体腺泡细胞分泌α淀粉酶和蛋白酶,其最有效浓度为1×10^-9mol/L。在相同摩尔条件下,琥珀酰-CCK7的促分泌效应明显大于CCK8,且这种效应在3小时内随着作用时间的延长而增加,这为开发高活性CCK8的类似物提供了依据。  相似文献   

2.
SNP抑制5-HT诱导的胞内游离钙浓度升高和内钙释放   总被引:2,自引:0,他引:2  
用Fura - 2/AM 荧光测量技术研究了5 - 羟色胺(5- HT) 诱导的大鼠尾动脉平滑肌细胞胞内钙升高和一氧化氮(NO) 的抑制效应。实验表明, 胞外0m mol/ L Ca2 + 时胞内静息[Ca2 + ] i 为20 .2±8 .6nmol/L(n = 8) 。10μmol/L 5- HT 可诱导出胞内钙库释放引起的瞬态[Ca2 +]i 升高,其峰值达245 .7 ±71.6nmol/ L(n = 6) 。10 - 7 mol/L 硝普钠(SNP) 可抑制5- HT 诱导的[Ca2 +]i 升高,其峰值浓度降为75.1±35 .9nmol/L(n = 5) 。当细胞浴液含2.5m mol/L Ca2 + 时,静息[Ca2 +]i为112 .8 ±10 .3nmol/ L(n = 5) , 这时10μmol/ L 5 - HT 可诱导[Ca2 + ] i 的峰值为252 .3 ±80 .6nmol/L(n = 4) ,以及其后平台浓度为143 .0 ±37 .6nmol/L(n = 4) ,略大于[Ca2 +]i 为112.8 ±10 .3nmol/L 的静息浓度,为外钙内流引起。10 - 7 mol/L SNP 也可抑制5- HT 诱导[Ca2 + ]i 平台相浓度。平台浓度由143 ±47  相似文献   

3.
本实验在分离培养的新生大鼠胰岛上,观察了胆囊收缩素(CCK-8)对白细胞介素-1β(IL—1β)损伤的胰岛β细胞功能的影响。并就其机制进行初步分析。结果表明:(1)IL—1β(5,10,20U/ml)能抑制葡萄糖(20mmol/L)刺激的胰岛素分泌,其抑制作用具有量效关系,抑制率分别为53.4%,60.5%和70.7%。(2)CCK-8对IL-1损伤的胰岛β细胞的功能具有保护作用。预防性地给予CCK-8(10 ̄(-10),10 ̄(-9),10 ̄(-8),10 ̄(-7)mol/L)能防止IL-1β对葡萄糖刺激的胰岛素分泌的抑制作用。治疗性地给予CCK-8也能恢复胰岛对葡萄糖刺激的胰岛素分泌的能力。(3)CCK A型受体阻断剂L364718(10nmol/L)能阻断CCK-8的保护作用,表明这一作用可能是通过CCK受体实现的。(4)IL-1β抑制胰岛素分泌的同时,能升高胰岛组织内cGMP水平,而CCK-8能阻止IL-1引起的cGMP水平的升高。  相似文献   

4.
乙酰胆碱对培养T细胞功能的作用   总被引:6,自引:0,他引:6  
邱一华  彭聿平 《生理学报》1995,47(3):275-280
本文研究不同浓度(10^-10-10^-4mol/L)乙酰胆碱(ACh)对离体培养的大鼠脾脏T淋巴细胞增殖的影响,并探讨其作用机制。实验结果表明:10^-9-10^-4mol/L可显著增强T细胞由刀豆素A(C-A)诱导的增殖反应,以10^-7-10^-6mol/L时最强。淋巴细胞先用ACh刺激1h或者刺激1h后洗弃ACh,再用ConA诱导6h的T细胞的增殖。10^-7-10-6mol/L阿托品可阻  相似文献   

5.
采用3H-TdR参入法,测定碱性成纤维细胞生长因子(bFGF)、胰岛素和内皮素-1(ET-1)对体外培养的大鼠肾小球系膜细胞(MC)增殖的影响,以及胰岛素与bFGF或ET-1促MC增殖的协同作用。结果表明,不同浓度的bFGF(5-200ng/ml)和胰岛素(0.1-2.4U/ml)均显著升高MC的3H-TdR参入值(cpm值)(P<0.01)。ET-1对MC的cpm值的影响依剂量不同呈现两种不同的效应,在10-9-10-7mol/L时,随着浓度的升高,MC的cpm值明显升高(P<0.01),并以10-8mol/L作用最强;当升高到10-6mol/L时,MC的cpm值出现降低趋势。胰岛素与bFGF或低浓度ET-1(≤10-8mol/L)共同作用于MC时,MC的cpm值明显高于二者单独作用之和(P<0.01),与高浓度ET-1(>10-7mol/L)共同作用于MC时,MC的cpm值小于二者单独作用之和(P>0.05)。上述结果说明,胰岛素、bFGF和ET-1均能显著促进MC增殖;胰岛素与bFGF或低浓度的ET-1促MC增殖具有正协同作用,与高浓度ET-1呈现负协同作用。  相似文献   

6.
内皮素-1对肺表面活性物质分泌的调控   总被引:4,自引:2,他引:2  
Luo ZQ  Sun XH 《生理学报》1998,50(3):333-336
采用离体大鼠非灌流肺,观察生理浓度内皮素-1对肺表面活性物质分泌的影响。结果表明,10^-12和10^-10mol/L的ET-1可促进PS磷脂及其主要组分磷脂酰胆碱的基础分泌;在间歇性肺扩张刺激基础上,ET-1可进一步加强磷脂和PC的分泌。蛋白激酶C抑制剂H7可阻断ET-1的促PS分泌效应。  相似文献   

7.
本文报道了[B1~Ala,B2-Ala]-胰岛素与人胎盘细胞膜胰岛素受体结合的特性和体外生物活力,并与胰岛素进行比较。在37℃和杆菌肽存在下,125I-[B1-Ala,B2-Ala]-胰岛素和125I-胰岛素与人胎盘细胞膜作用依赖于反应时间,反应6分钟到达平衡,此时,[B1-Ala,B2-Ala]-胰岛素和胰岛素与胰岛素受体的最大结合分别为每毫克膜蛋白结合6.44fmol和3.47fmol:达到平衡一半所需时间(T1/2)分别为19秒和25秒。用125I-[B1-Ala,B2-Ala]-胰岛素作为放射配体进行竞争性结合研究,从IC(50)得[B1-Ala,B2-Ala]胰岛素的受体结合活力为胰岛素的139.6%。Scatohard分析求得;[B1-Ala,B2-Ala]-胰岛素与高亲和和低亲和结合位点的结合常数在4℃时分别为5.88×108L/mol和7.63×105L/mol,而胰岛素分别为4.83×108L/mol和3.39×105L/mol。促脂肪细胞生成脂的实验表明:[B1-Ala,B2-Ala]-胰岛素的活力为胰岛素的130%。  相似文献   

8.
本研究着重探讨表皮生长因子(EGF)对大鼠肺动脉的收缩作用及对肺动脉平滑肌细胞分裂增殖的影响。浓度为1×10-9-1×10-7mol/L的EGF可引起大鼠肺动脉剂量依赖性收缩(r=0.968,P<0,001),其Emax为100.6mg,EC50为11.96nmol/L。在同时存在0.5%胎牛血清(FCS)时,EGF能促进平滑肌细胞的3H-TdR参入率,该作用与剂量呈正相关(r=0.823,P<0.05),其EC50为6.5×1O-12mol/L。1×10-9mol/L的EGF+0.5%FCS能产生与10%FCS相当的促细胞分裂增殖能力(在培养的第1,3,5,7天,二者促分裂增殖能力相差不明显,P均>0.05,第9天时,前者大于后者,P<0.05)。1×10-9mol/LEGF单独存在时对平滑肌细胞未显示出明显的致分裂活性。上述作用提示ECF在某些肺血管病变如缺氧性肺动脉高压中可能有一定意义。  相似文献   

9.
利用大鼠颅骨开窗观察软脑膜微循环的方法研究了内皮素(ET-1)10^-10-10^-7mol/L对软脑膜微循环的影响以及失血性体克时软脑膜对ET-1的反应性。并用10^-7mol/L造成失血性休克后脑血管痉挛的模型,观察尼莫地平、川芎嗪、654-2对内皮素引起血管痉挛的治疗作用。10^-9,10^-8和10^-7mol/L3种浓度ET-1可使脑膜小动脉、细动脉强烈收缩,收缩率分别为27.7%、46  相似文献   

10.
乙酰胆碱对大鼠体外抗体生成的影响   总被引:2,自引:1,他引:1  
目的:观察不同浓度乙酰胆碱(ACh,10-10~10-5mol/L)对大鼠体外抗体生成的影响,并初步探讨其作用机制,从细胞水平了解乙酰胆碱与免疫功能之间的关系。方法:用体外抗体生成的检测方法,用绵羊红细胞(SRBC)刺激大鼠肠系膜淋巴结B细胞转化成抗体形成细胞(AFC),然后检测其抗体生成量。结果:①10-10~10-7mol/LACh能显著抑制体外抗体生成,其中10-8和10-7mol/LACh的作用较强,而10-6和10-5mol/LACh无明显的抑制作用;②M型胆碱能受体激动剂毛果芸香碱(10-8和10-7mol/L)能明显减弱体外抗体生成,而N型受体激动剂烟碱(10-8和10-7mol/L)没有显著的减弱作用,M型受体拮抗剂阿托品(10-7和10-6mol/L)可完全阻断ACh抑制体外抗体生成的作用;③ACh分别在B细胞用SRBC刺激后3~48h中的6个不同时间与淋巴细胞作用,其抗体生成仍然是减少的。结论:ACh可非浓度依赖性地抑制大鼠的体外抗体生成;此作用可能由B细胞上的M型胆碱能受体介导;且ACh可能主要影响B细胞转化的后期过程。  相似文献   

11.
So far, there are no known peptidic effective receptor antagonists of both peripheral and central effects of cholecystokinin (CCK). Here, we describe a synthetic peptide derivative of CCK, t-butyloxycarbonyl-Tyr(SO3-)-Met-Gly-D-Trp-Nle-Asp 2-phenylethyl ester 1 (where Nle is norleucine), which is a potent CCK receptor antagonist. In rat and guinea pig dispersed pancreatic acini, this peptide derivative did not alter amylase secretion, but was able to antagonize the stimulation caused by cholecystokinin-related agonists. It caused a parallel rightward shift in the dose-response curve for the stimulation of amylase secretion with half-maximal inhibition of CCK-8-stimulated amylase release at a concentration of about 0.1 microM. Compound 1 was able to inhibit the binding of labeled CCK-9 (the C-terminal nonapeptide of CCK) to rat and guinea pig pancreatic acini (IC50 = 5 X 10(-8) M) as well as to guinea pig cerebral cortical membranes (IC50 = 5 X 10(-7) M). These results indicate that Compound 1 is a potent competitive CCK receptor antagonist.  相似文献   

12.
The rat plasma cholecystokinin (CCK) concentration was measured after intestinal administration of a peptide purified from rat bile-pancreatic juice, which has a stimulatory effect on pancreatic enzyme secretion. The plasma CCK concentration was measured by means of a radioimmunoassay using CCK-8 N-terminal specific antibody, OAL-656. In experimental rats with protease-free intestines, intraduodenal infusion of 10 micrograms of the purified peptide, which stimulates pancreatic enzyme secretion 2.0-2.5 fold, induced a significant increase in the plasma CCK level. Furthermore, after removal of CCK from the plasma by immunoabsorption with an OAL-656-bound Sepharose 4B column, the stimulatory effect of the plasma on pancreatic enzyme secretion was abolished when it was injected intravenously into recipient rats. It was concluded that this peptide stimulates the release of CCK in the intestine and that this is responsible at least in part for the pancreatic enzyme secretion-stimulating activity of the peptide.  相似文献   

13.
Immunoreactive cholecystokinin (CCK) levels in human and rat plasma are described using a radioimmunoassay specific for the biologically active sulfated end of CCK. This assay detected significant changes in plasma cholecystokinin levels during intrajejunal administration of amino acids and intravenous infusions of CCK-8 which were followed by increased pancreatic secretion. In humans, the concentration (pg/ml) of plasma cholecystokinin increased from 10.8 to 18.9 following intrajejunal amino acid instillation and from 15.4 to 31.1 during CCK infusion, while pancreatic trypsin secretion increased more than 15 fold. Ingestion of a test meal also caused a rapid and significant elevation (P less than 0.05) in both plasma CCK (14.5-21.7 pg/ml) and gastrin (50-160 pg/ml) levels. In the rat, an injection of 46 ng of CCK-8 produced a 300% increase in immunoreactive plasma CCK levels (2 min) and caused peak pancreatic protein secretion within 5 min; 4 fold lower doses (11.5 ng) elevated plasma CCK by 38% and pancreatic protein secretion to a small but significant extent. The ability of this assay to detect various forms of sulfated CCK in human plasma was also determined. Following gel chromatography on Sephadex G-50, at least three different immunoreactive peaks were found in plasma from fasted subjects and after intrajejunal amino acid stimulation. While the lower molecular weight CCK peptides (CCK-8 and CCK-12) were detected in plasma from both fasted and stimulated subjects, the larger form (CCK-33) was only present in measurable concentrations after amino acid infusion. The simultaneous measurement of increased plasma CCK levels and pancreatic secretion and the changes in the distribution of CCK peptides following amino acid infusion provides strong support that this assay detects physiologically relevant changes in biologically active CCK peptides.  相似文献   

14.
Isolation of pure acinar cells of the rat pancreas was achieved employing counterflow sedimentation filtration technique (CSFT). The preparation of purified acinar cells contained an occasional red blood cell (RBC, 200:1) with total absence of endocrine and duct cells. A significant stimulation of amylase secretion from isolated pure acinar cells was produced by octapeptide of cholecystokinin (CCK8) and insulin produced potentiation of the effect of CCK8. Synthetic glucagon inhibited basal and CCK8 stimulated amylase secretion. Non-synthetic purified glucagon stimulated amylase secretion and potentiated the effect of CCK8. Vasoactive intestinal polypeptide (VIP) did not stimulate amylase secretion but potentiated the effect of CCK8. No leakage of lactic dehydrogenase (LDH) was detected from the cells in any of the secretion studies. Thus a highly purified preparation of isolated pure acinar cells of rat pancreas could be obtained with excellent morphologic and functional integrity.  相似文献   

15.
Leptin originally described as product of the ob gene has been shown to be expressed in various tissues including the gastrointestinal tract. In this study, we investigated the influence of leptin on the secretion of pancreatic juice in biliary-pancreatic duct cannulated anaesthetised rats and in dispersed rat pancreatic acini in vitro. Exogenous leptin was given in boluses intravenously with or without CCK-8 (12 pmol kg(-1) body weight) in the presence or absence pharmacological CCK(1) receptor blockade, cervical vagotomy, and capsaicin pre-treatment. Administration of leptin (0.1, 1 and 10 microg kg(-1) body weight) did not affect the volume of bile and pancreatic juice while the protein and trypsin outputs were reduced in a dose-dependent manner. In the rats, leptin inhibited CCK-8 stimulated protein and trypsin outputs stronger than the basal pancreatic secretion. The inhibition by leptin was abolished by the pharmacological CCK(1) receptor blockade, cervical vagotomy, and capsaicin pre-treatment. In contrast, leptin did not affect basal and CCK-8-stimulated amylase release from the dispersed rat pancreatic acini in vitro. In conclusion, the results of the present study suggest that leptin does not act directly on the rat pancreatic acinar cells but inhibits the secretion of pancreatic enzymes acting indirectly via a neurohormonal CCK-vagal-dependent mechanism.  相似文献   

16.
 为阐明中枢神经系统中胆囊收缩素 8(CCK8)受体的信号传递机制 ,以分离的大鼠大脑皮质神经细胞为材料 ,观察了CCK8对细胞内钙调素 (CaM)、3′ ,5′ 环腺苷酸 (cAMP)、蛋白激酶C(PKC)活性的影响 研究结果表明 ,CCK8可刺激大脑皮质细胞CaM、PKC活性的增加 ,并有剂量依赖关系 但CCK8在 10 -12 ~ 10 -6mol L范围内 ,细胞内cAMP含量无显著变化 利用受体亚型L 364,718和L 365,2 60的研究表明 ,两种拮抗剂均可抑制CCK8引起的CaM和PKC活性变化 ,但两者IC50 不同 对于CaM ,CCKB 受体拮抗剂L 365,2 60的IC50 比CCKA 受体拮抗剂L 364,718低 4 0倍 ;而对于PKC ,L 365,2 60的IC50 比L 364,718低 60倍 因此认为 ,CCK8主要是通过CCKB 受体介导了CaM和PKC活性的变化  相似文献   

17.
The G protein-coupled cholecystokinin 1 receptor (CCK1R) is activated permanently by type II photodynamic action (i.e., by singlet oxygen) in the freshly isolated rat pancreatic acini, in contrast to reversible activation by CCK. But how CCK1R is photodynamically activated is not known. Therefore, in the present work, we subjected membrane proteins extracted from isolated rat pancreatic acini to photodynamic action with photosensitiser sulphonated aluminium phthalocyanine (SALPC), and used reducing gel electrophoresis and Western blot to detect possible changes in CCK1R oligomerization status. Photodynamic action (SALPC 1 µM, light 36.7 mW cm??2 × 10 min) was found to convert dimeric CCK1R nearly quantitatively to monomers. Such conversion was dependent on both irradiance (8.51–36.7 mW cm??2) and irradiation time (1–20 min). Minimum effective irradiance was found to be 11.1 mW cm??2 (× 10 min, with SALPC 1 µM), and brief photodynamic action (SALPC 1 µM, 36.7 mW cm??2 × 1 min) was effective. Whilst CCK stimulation of purified membrane proteins alone had no effect on CCK1R dimer/monomer balance, sub-threshold photodynamic action (SALPC 100 nM, 36.7 mW cm??2 × 10 min) plus CCK revealed a bell-shaped CCK dose response curve for CCK1R monomerization, which was remarkably similar to the dose response curve for CCK-stimulated amylase secretion in isolated rat pancreatic acini. These two lines of evidence together suggest that during photodynamic CCK1R activation, CCK1R is permanently monomerized, thus providing a unique approach for permanent G protein-coupled receptor (GPCR) activation which has not been achieved before.  相似文献   

18.
The effect of newly discovered pancreastatin on pancreatic secretion stimulated by a diversion of bile-pancreatic juice (BPJ) from the intestine was examined in the conscious rat. Exogenous pancreastatin infusion (20, 100 and 200 pmol/kg.h) inhibited pancreatic protein and fluid outputs during BPJ diversion in a dose-dependent manner. Pancreastatin did not affect plasma cholecystokinin (CCK) concentrations. Pancreastatin (100 pmol/kg.h) inhibited CCK-stimulated pancreatic secretion, but did not inhibit secretin-stimulated pancreatic secretion. Pancreastatin alone, however, did not affect basal pancreatic secretion. In contrast, pancreastatin (10(-10)-10(-7)M) did not suppress CCK-stimulated amylase release from isolated rat pancreatic acini. These results indicate that pancreastatin has an inhibitory action on exocrine function of the pancreas. This action may not be mediated by direct mechanisms and nor via an inhibition of CCK release. It is suggested that pancreastatin may play a role in the regulation of the intestinal phase of exocrine pancreatic secretion.  相似文献   

19.
Four healthy Holstein heifers (235 ± 12 kg) fitted with duodenal and pancreatic cannulas were used to investigate infusion of isoleucine (Ile) on the pancreatic exocrine function in a 4 × 4 Latin square design. Three doses of Ile, 10, 20 and 30 g in 2500 ml water, respectively, were infused into the duodenum over a period of 12 h in Experiment (Exp) 1 and over 10 d in Exp 2. Hourly pancreatic juice and jugular blood were taken during the infusion period in Exp 1, and the blood samples were taken in 2-h intervals over the last 2 d in Exp 2. Compared with no Ile infusion, the Ile infusions in both experiments increased the concentration and secretion rate of the protein, activity of ɑ-amylase and trypsin and plasma cholecystokinin. The secretion rate of ɑ-amylase and the activity of trypsin linearly increased with the Ile doses. The pancreatic juice secretion linearly increased with Ile in Exp 2 but not in Exp 1. Isoleucine linearly increased plasma insulin in Exp 1, but not in Exp 2. No effects of Ile on pH of pancreatic juice, the activity of chymotrypsin and lipase and plasma glucose were found. In conclusion, duodenal Ile infusion could increase the pancreatic exocrine function of Holstein heifers, especially ɑ-amylase, and the increment appeared to be dose and time dependent.  相似文献   

20.
This study determines the effect of 7-day pretreatment with L364,718 (a potent cholecystokinin (CCK) receptor antagonist) on pancreatic cell turnover during the course of acute pancreatitis (AP) induced in the rat by bile-pancreatic duct obstruction (BPDO). Cell cycle distribution and apoptosis were analyzed by flow cytometry using propidium iodide (PI) and Annexin V staining. Besides altering the pancreatic redox status, long-term CCK blockade inhibited the normal proliferation of acinar cells as indicated by the significant increase in G(0)/G(1)-phase cells and the decrease in G(2)/M-cells found in control rats treated with L364,718 for 7 days. A progressive depletion in pancreatic GSH was found from 3 to 24h after BPDO with similar values in L364,718-pretreated and non-treated rats, which led to a maximum peak in malondialdehyde (MDA) levels 6h after BPDO. However, plasma amylase activity and ascites volume indicated higher severity of AP in L364,718-pretreated rats. CCK blockade enhanced the alterations that appear in cell cycle distribution of acinar cells during AP demonstrated by the significantly higher increase in G(0)/G(1)-cells and decrease in S-cells found in L364,718-treated rats 48h after BPDO. Our results indicate that the renewal of acinar cells deleted by apoptosis 48h after BPDO worsens if CCK is blocked before inducing AP.  相似文献   

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