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1.
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   

2.
中枢5-羟色胺缺损引起的高血压及其中枢机理   总被引:1,自引:0,他引:1  
目的:建立中枢5羟色胺(5-HT)缺损所致的实验性高血压大鼠(EHR)模型并探讨其中枢机理。方法:侧脑室埋植瘘管及药物注射。大鼠尾动脉血压及心率启示仪记录清醒大鼠动脉压(AP)及心率(HR)。高效液相色谱-电化学检测法HPLC-ECD)检测大鼠脑内单胺类递质含量。结果:(1)给大鼠侧脑室(ICV)注射选择性神经化学切除剂5,6-双羟色胺(5,6-DHT)引起中枢5-HT神经元缺损,使脑同5-HT含  相似文献   

3.
本工作目的是在离体大鼠肠系膜动脉床灌流模型上,观察几种常见炎症介质:前列腺素E2(PGE2)、缓激肽(BK)、组胺(HIS)、血小板活化因子(PAF)及5-羟色胺(5-HT)对血管周围感觉神经介质CGRP释放的直接影响。结果显示:PGE2(1-100μmol/L)和BK(5-10μmol/L)能引起大鼠肠系膜动脉床时间和浓度依赖性地释放CGRP。HIS,PAF和5-HT则未见明显作用。结果提示,PGE2与BK可能是引起血管周围感觉神经兴奋和CGRP释放的主要炎症介质。  相似文献   

4.
5—羟色胺转运体研究进展   总被引:2,自引:0,他引:2  
5-羟色胺(5-HT)是中枢及外周神经系统中一种重要的神经递质,具有多种生物活活性。5-羟色胺转运体(5-HTT)可将5-HT重摄取,降低胞外5-HT浓度。近来发现5-HTT功能异常与某些精神疾病和可卡因成瘾性有关,因此开发对5-HTT具有高亲和力与高选择性的药物在临床上很有意义。目前5-HTT已在大鼠和人中克隆,这不仅有助于阐明配体与5-HTT作用的分子机制,同时也为药物设计提供了方向。  相似文献   

5.
5—羟色胺免疫调节作用研究进展   总被引:13,自引:0,他引:13  
Yang GB 《生理科学进展》1997,28(4):349-351
5-羟色胺(5-HT)在体内广泛分布并具有多种生物学活性。近年许多研究表明5-HT可以通过受体作用于T、B淋巴细胞、NK细胞和MХ;对DTH、NKCC、淋巴细胞增殖活性和MХ吞噬活性均有调节作用,是神经内分泌免疫调节网络的重要成分。  相似文献   

6.
褪黑素对大鼠海马神经元谷氨酸所致毒性的拮抗作用   总被引:3,自引:0,他引:3  
在大鼠海马脑片上电刺激Schaffer 侧支纤维, 胞外记录CA1 区锥体细胞层诱发群体锋电位(population spike,PS) , 观察灌流谷氨酸(Glu) 和褪黑素(MEL) 对PS的影响。结果显示:5-0 mmol/L浓度的Glu 可使PS值下降至对照值的4-1 % ; MEL(0-4 、0-5 和0-6 μmol/L) 与5-0 mmol/LGlu 混合给药,PS值分别变化为对照值的14-7 % 、105-2% 、24-3 % ; MEL(0-5 μmol/L) 、Glu (5-0 mmol/L) , 与赛庚啶(CDP,0-5 μmol/L) 混合给药,PS值下降至0 。上述结果提示,5-0 mmol/L浓度的Glu 有神经毒性作用, 但可为MEL拮抗, 这可能由5HT受体所介导。  相似文献   

7.
交感神经节细胞对P物质和5-羟色胺的反应   总被引:3,自引:0,他引:3  
Cai SR  Wang LC  Kong DH  Huang ZX  Ma RC 《生理学报》1999,51(5):585-587
本工作旨在观察P物质(SP)受体与5-羟色胺(5-HT)受体是否分别还是同时存在于豚鼠腹腔神经节(CG)与肠系膜下神经节(IMG)不同细胞,以及这两种递质之间是否存在相互作用。在133个CG细胞中,66个(49.6%)对SP及5-HT同时敏感,40个(30.1%)仅对其中一种递质敏感,此外27个(20.3%)对两都不敏感。  相似文献   

8.
在74张大鼠下丘脑脑片上,用玻璃微电极记录到弓状核自发放电单位176个,其放电形式有三种:慢不规则型(119个,67.6%);快连续型(46个,26.1%);位相型(11个,6.3%)。5-HT(10-6mol/L,3min)对不同形式放电单位的作用均以抑制为主:对部分慢不规则单位(9/119)则表现为先抑制后兴奋的双相性反应,对少数神经元有兴奋作用。12个被5-HT抑制的单位,其抑制作用不能被噻庚啶(CHD,10-5mol/L)阻断,4个被5-HT抑制的的单位中,其抑制作用可被二甲基麦角新碱(MSG10-6mol/L)部分或完全阻断。7个被5-HT抑制的单位,其中4个单位中,5-HT的抑制作用可被特异性5-HT1A受体阻断剂Pindobind-5-HT1A部分阻断;但另外3个单位的阻断效果不明显。上述结果表明:5-HT对弓状核不同形式放电单位的作用均以抑制为主,其作用可能是通过5-羟色胺(5-HT1)受体介导的,部分还可能是通过5-HT1A受体介导的。  相似文献   

9.
以逆行追踪与免疫细胞化学相结合法,探讨了大鼠提睾肌、盲肠系膜和耳廓等微循环研究常用部位的神经肽Y(NPY)、降钙素基因相关肽(CGRP)、甲啡吠(M-END)和5-羟色胺(5-HT)等肽能和胺能神经的支配。结果表明:支配提睾肌的运动和感觉神经元分别含有5-HT和CGRP。支配提睾肌血管、盲肠系膜及其血管的交感神经元,一部分含有NPY,一部分含有M-ENK;支配耳廓局部的运动和感觉神经元均含有CGR  相似文献   

10.
本文采用作者建立了放射免疫测定法,测定了16只大白鼠消化道不同部位粘膜中胃动素Moti-lin(MTL)含量和血浆MTL含量。结果表明:贲门表明:贲门粘膜中MTL含量最高,并依次为胃体,幽门、十二指肠、小肠。经统计学处理,贲门与胃白组,幽门与十二指肠组,十二指肠与小肠组均呈显著性差异。  相似文献   

11.
The role of motilin in the generation of the gastric component of phase 3 of the migrating myoelectric complex (MMC) was studied in human volunteers. Interdigestive motor activity was recorded manometrically in five normal subjects after a fast of at least 15 h. Intraluminal pressures were measured in the gastric antrum at 4 levels 3 cm apart and in the upper small bowel at 3 levels 25 cm apart. Blood samples were drawn every 10 min for radioimmunoassay of motilin and PP. After 2 spontaneously occurring activity fronts (AF) had been recorded, bovine PP was infused intravenously at a rate of 50 μg/h. Following the third AF a combination of PP (50 μg/h) and 13-norleucine-motilin (30 μg/h) was infused until after the next AF. It was found that 90% of the spontaneous AFs originated in the stomach. They were preceded by a motilin peak. During the PP infusion, plasma PP levels increased from 29 to 256 pmol/l, motilin decreased from 42 to 15 pmol/l, and all AFs originated in the small bowel. During the combined PP and motilin infusion, plasma motilin increased to 330 pmol/l, and all AFs again originated in the stomach. It is concluded that motilin has an important role in the regulation of the MMC activity front in the stomach, but not in the small intestine. Postprandial rises in plasma PP might be involved in lowering motilin levels after a meal, and indirectly, in the disruption of gastric MMCs during digestion.  相似文献   

12.
The peripheral plasma concentrations of immunoreactive motilin, pancreatic polypeptide (PP), somatostatin and gastrin were measured in 7 pigs fasted to 24 h and subsequently fed a standard meal. Plasma motilin peaked during the last part of phase II activity of the migrating myoelectric complex (MMC) sequence (25.2 +/- 2.3 pM), the lowest value being recorded during phase I (10.6 +/- 1.5 pM) after a 24 h fast. Plasma motilin remained at a low level during the digestive pattern of duodenal activity, no fluctuation occurring when the first postprandial MMC recurred. At variance analysis, gastrin and PP were not released phasically with MMC in the fasting state, while at autocovariance both peptides tended to fluctuate during the MMC sequence with positive and negative peaks at regular intervals along MMC cycles. No variation of plasma somatostatin was observed in the fasting animals. These findings argue against a major role of circulating PP, gastrin and somatostatin-like components in the control of fasted and post absorptive duodenal motility in pigs while the role of motilin remains equivocal.  相似文献   

13.
Pharmacokinetics of 3H-cicaprost in healthy volunteers   总被引:1,自引:0,他引:1  
Cicaprost (5-[(E)-(1S,5S,6S,7R)-7-hydroxy-6-[(3S,4S)-3-hydroxy-4-methylnona- 1,6- diinyl]-bicyclo[3.3.0]octan-3-yliden]-3-oxapentanoic acid, ZK 96 480) is a novel PGI2-derivative, which is chemically stable and not subject to metabolic degradation in rats and cynomolgus monkeys. The pharmacokinetics of Cicaprost were studied in six healthy volunteers (age: 54-74 y) after i.v. infusion (2.1 micrograms over 60 min) and p.o. dosage (7.6 micrograms) of the tritiated compound. All treatments were well-tolerated by the test subjects. At the end of the infusion plasma levels of approximately 100 pg/ml were reached, declining biphasically with half-lives of 3-4 min and 64 +/- 21 min. Total clearance was 3.8 +/- 0.5 ml/min/kg. The oral dosage resulted in peak plasma levels of 251 +/- 90 pg/ml occurring at 23 +/- 5 min post dose. The terminal half-life in the plasma was 115 +/- 30 min. Gastro-intestinal absorption and absolute bioavailability of Cicaprost was complete. After both routes of administration approx. 60% of dose was excreted with the urine within 24 h, whereas fecal 3H-excretion lasted for several days and accounted for approx. 35%. Radiochromatography revealed that Cicaprost was metabolically stable in plasma and urine. In the feces several degradation products were observed apart from approx. 30% of the dose fraction being excreted unchanged by that route. The present results demonstrate that Cicaprost is an orally completely bioavailable, metabolically stable PGI2-mimetic which may be an ideal candidate for oral therapy because of its pharmacokinetic characteristics.  相似文献   

14.
Indicator dilution technique was used to study effects of reduced vascular volume or acute injury on removal of low doses of [3H]propranolol and [14C]serotonin (5-hydroxytryptamine, 5-HT) by perfused rabbit lung. Glass-bead (500 micron) embolization doubled pulmonary arterial pressure (Ppa) at flow rates of 20, 50, and 100 ml/min, decreased volume of distribution by approximately 50%, and increased pulmonary vascular resistance by at least 60%. Before embolization, (flow rate 20 ml/min) removal of [3H]propranolol and [14C] 5-HT was 89 +/- 2 and 75 +/- 5%, respectively, and was unaltered by changes in flow rate. However, after embolization, [3H]propranolol and [14C]5-HT removal decreased in a flow-dependent manner, reaching 28 +/- 4 and 1 +/- 3% (P less than 0.05), respectively, at a flow rate of 100 ml/min. When phorbol myristate acetate (PMA, 200 nM) was perfused (50 ml/min) through the lungs for 15 min, Ppa increased from 13 +/- 1 to 25 +/- 2 cmH2O (P less than 0.05), whereas [3H]propranolol removal decreased from 92 +/- 1 to 75 +/- 5% (P less than 0.05) and [14C]5-HT removal decreased from 73 +/- 3 to 46 +/- 8% (P less than 0.05). The PMA also caused vasoconstriction, which could be partially blocked by adding papaverine (500 microM) to the perfusion medium. Under the latter conditions, Ppa increased to 19 +/- 1 cmH2O and [3H]propranolol removal was unaffected. However, the combination of PMA and papaverine reduced [14C]5-HT removal from 64 +/- 4 to 19 +/- 3%.(ABSTRACT TRUNCATED AT 250 WORDS)  相似文献   

15.
During the follicular phase of bactrian camels, basal concentrations of LH were 2.7 +/- 1.2 ng/ml. By 4 h after insemination peak values of 6.9 +/- 1.0 ng/ml occurred. In addition, a smaller LH peak (5.4 +/- 2.5 ng/ml) appeared 1 day before regression of the follicle began in unmated camels. During the follicular phase peripheral plasma progesterone values were low (0.36 +/- 0.28 ng/ml), but values increased to reach 1.73 +/- 0.74 ng/ml at 3 days and 2.4 +/- 0.86 ng/ml at 7 days after ovulation. Plasma oestradiol-17 beta concentrations were 26.8 +/- 9.0 pg/ml during the follicular phase and 30.8 +/- 5.1 pg/ml when the follicle was maximum size. Values fell after ovulation but rose to 29.8 +/- 6.5 pg/ml 3 days later.  相似文献   

16.
A sensitive, reliable and simplified HPLC assay for simultaneous measurement of 5-hydroxytryptamine (5-HT) and 5-hydroxyindoleacetic acid (5-HIAA) in human cerebrospinal fluid (CSF), platelets and plasma is described. Perchloric acid is used for one step precipitation of proteins and extraction of 5-HT and 5-HIAA. Precision of the assay has been increased by calibration of the instrument using serotonin-free plasma spiked with known amount of standards and N-w-methyl-5-hydroxytryptamine as internal standard. Integration of the peaks and calculations are achieved by a preprogrammed data module using ratio method. As little as 20 pg/ml of serotonin in the deproteinated sample can be detected using this procedure. In a group of surgical patients, plasma 5-HT concentration is (Mean +/- S D) 3.4 +/- 2.7 ng/ml and that of platelet 748.3 +/- 448.3 ng/10(9) platelets. In CSF, 5-HT is found to be 3.3 +/- 3.4 ng/ml and 5-HIAA is 15.1 +/- 7.3 ng/ml. A good correlation (r = 0.648, p less than .0001) is observed between 5-HT and 5-HIAA in CSF.  相似文献   

17.
Changes in canine plasma glucose, immunoreactive glucagon (IRG), pancreatic polypeptide (PP) and insulin (IRI) were studied during the acute development of diabetes mellitus after iv alloxan injection. 100 mg or 75 mg/kg body weight of alloxan was injected iv and blood was taken successively till one or two days later. Plasma glucose showed four phases: first immediate and moderate decrease appeared 30 min after injection, second initial hyperglycemic phase, third hypoglycemic and fourth diabetic ones. Plasma IRI had already increased to 182 +/- 60 microU/ml 10 min after injection and again began to increase after about 6 h, peaking to 134 +/- 49 microU/ml at 18 h. Plasma IRG began increasing gradually soon after alloxan injection. The initial value was 196 +/- 26 pg/ml and it increased to 534 +/- 144 pg/ml at 4 h during the initial hyperglycemic phase, then reached a higher level through the hypoglycemic and diabetic phases. The change in plasma PP was similar to that in IRG. The initial value was 256 +/- 95 pg/ml at 12 h after injection, peaking to 840 +/- 100 pg/ml in the hypoglycemic phase. Similar blunted values were obtained following 75 mg/kg alloxan injection. Thus not only plasma IRI but also plasma IRG and PP varied greatly during the acute development of alloxan diabetes and some contribution of IRG to the initial hyperglycemic phase was suggested.  相似文献   

18.
Steady-state model for plasma free and platelet serotonin in man   总被引:3,自引:0,他引:3  
A steady-state physiological flow model has been developed for predicting plasma free serotonin (5-HT), and platelet 5-HT, concentrations in man. The basic assumptions of the model are that 5-HT is produced in the wall of the intestine, enters the portal circulation at a constant rate, and is cleared by the lung, liver, kidney, and capillary bed. When a priori best estimates of the 5-HT production rate and organ extraction efficiencies were substituted into formulae describing the model, a predicted value for plasma free 5-HT of 304 pg/ml was obtained, in good agreement with a previously observed mean (+/- SE) of 387 +/- 84 pg/ml. The effects of varying production rate and extraction efficiency parameters on predicted levels of plasma free 5-HT are examined. The practical implications of the model and its possible utility in elucidating the causes of altered plasma free or platelet 5-HT seen in certain conditions are discussed.  相似文献   

19.
Circulating met-enkephalin-like immunoreactivity (MLI) rises in man after chlorpropamide and ethanol although the origin and molecular forms of circulating MLI are not well defined. We have studied the response to oral ethanol in conscious and anaesthetised dogs pretreated with chlorpropamide. In conscious dogs MLI rose from a basal level of 29 +/- 7 pg/ml to a peak of 55 +/- 14 pg/ml 10 min after ethanol (P less than 0.001). In anaesthetised animals, following ethanol, plasma MLI rose in caval (35 +/- 6 pg/ml to a peak of 70 +/- 10 pg/ml), in portal (28 +/- 6 pg/ml to 51 +/- 6 pg/ml) and in adrenal blood (897 +/- 316 pg/ml to 1483 +/- 298 pg/ml; P less than 0.001). Biogel P-4 chromatography of caval and portal basal plasma showed 87% of MLI measured coeluted with the synthetic pentapeptide, while chromatography of peak plasma showed that only 65% coeluted with the pentapeptide and the remaining 35% was of larger molecular size. Sephadex G75 chromatography of adrenal vein plasma revealed three peaks of MLI of differing molecular sizes (8 k = 69.7%; 3-5 k = 12.1% and the pentapeptide = 18.2%). Treatment of the column fractions with trypsin and carboxypeptidase B resulted in the generation of new MLI with peaks of approximate molecular sizes 31 k (10.4%), and 18 k (37.1%) in addition to 8 k (40.0%), 3-5 k (5.0%) and the pentapeptide (7.5%). Acetaldehyde involvement in MLI release was investigated. Following acetaldehyde infusion, plasma MLI rose both in caval (35 +/- 9 pg/ml to 86 +/- 8 pg/ml) and adrenal vein (417 +/- 121 pg/ml to 1768 +/- 433 pg/ml) bloods. Thus we have established an animal model which enables further study of the mechanisms of MLI release and characterisation of the molecular forms. The adrenal medulla, unlike the gut, may be an important source of circulating met-enkephalin and acetaldehyde formation an essential intrinsic component of chlorpropamide-ethanol induced met-enkephalin release.  相似文献   

20.
We tested the possibility that neuropeptide Y (NPY) may contribute to the pulmonary hypertension that occurs after massive sympathetic activation produced by intracisternal veratrine administration in the chloralose-anesthetized dog. In six dogs, veratrine caused arterial NPY-like immunoreactivity (NPY-LI) to rise from 873 +/- 150 (SE) pg/ml to peak values of 3,780 +/- 666 pg/ml by 60-120 min. (In 3 animals, adrenalectomy significantly reduced the increases in NPY-LI.) In five additional dogs, we infused porcine NPY for 30 min in doses that increased arterial NPY-LI to 8,354 +/- 1,514 pg/ml and observed only minor changes in pulmonary hemodynamics. In three isolated perfused canine left lower lung lobe (LLL) preparations, increasing doses of NPY were administered, producing levels of plasma NPY-LI, at the highest dose, that exceeded those observed after veratrine administration by three orders of magnitude. No changes in LLL arterial or double-occlusion capillary pressures were observed at any dose. Similarly, no changes in LLL hemodynamics were observed in three additional lobes when NPY was administered while norepinephrine was being infused. We conclude that it is unlikely that NPY plays a role as a circulating vasoactive agent in producing the pulmonary hypertension and edema that occur in this model.  相似文献   

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