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11.
S. L. Grant P. A. Phillips C. B. Gow 《Clinical and experimental pharmacology & physiology》1994,21(3):243-247
1. Epidermal growth factor is a potent mitogen that causes natriuresis, diuresis and inhibition of arginine vasopressin-induced water reabsorption. 2. The aim of this study was to determine any interaction between epidermal growth factor and the V1 (vascular) and/or V2 (antidiuretic) arginine vasopressin receptor subtypes. 3. Radioligand binding displacement assays demonstrated that although arginine vasopressin related peptides displaced both radioligands from renal medullary membranes at low concentrations epidermal growth factor displaced neither. 4. Arginine vasopressin V2 receptor second messenger cyclic adenosine monophosphate (CAMP) production was inhibited by epidermal growth factor (IC50 2 ± 10?7 mol/L) as was sodium fluoride cAMP production but only at much higher concentrations. 5. Therefore the diuretic effect of epidermal growth factor is not via direct antagonism of arginine vasopressin receptors but seems mediated via inhibition of the V2 second messenger system. 相似文献
12.
MARINA GOBBO LAURA BIONDI FERNANDO FILIRA TOM PIEK RANIERO ROCCHI 《Chemical biology & drug design》1995,45(5):459-465
Syntheses are described of the endo-Lys8a-vespulakinin 1 and of cyclo-Thr6- and cyclo-Nε-Lys-bradykinin. The linear peptides covering the entire sequences of endo-Lys8a-VSK-1 and Thr6-BK, and the decapeptide containing all residues constituting Lys-BK, with a Arg-Lys peptide bond involving the ε-amino function of lysine, were prepared by the solid-phase procedure based on Fmoc chemistry. Cyclization was carried out by the diphenylphosphorazide method. The amino-terminal octapeptide sequence of vespulakinin 1, Fmoc-Thr(tBu)-Ala-Thr(tBu)-Thr(tBu)-Arg(Pmc)-Arg(Pmc)-Arg(Pmc)-Gly-OH, and its Nα-Boc-[(Gal β)Thr3, (Gal β)Thr4]-analogue, were used to prepare Nα-(1–8 VSK 1)-cyclo-Nε-kallidin and Nα-[(Gal β)Thr3, (Gal β)Thr4, 1–8 VSK 1]-cyclo-Nε-kallidin. Peptides and glycopeptides were characterized by amino-acid analysis, optical rotation, analytical HPLC and FAB-MS. Consistent with previous findings, preliminary pharmacological experiments on smooth muscle preparations showed that the cyclic, or partially cyclic, analogues were significatively less potent than the linear ones. © Munksgaard 1995. 相似文献
13.
N. Griffon C. Pilon F. Sautel J. -C. Schwartz P. Sokoloff 《Journal of neural transmission (Vienna, Austria : 1996)》1996,103(10):1163-1175
Summary In NG 108-15 cells expressing the recombinant human D3 receptor, dopamine agonists enhance [3H]thymidine incorporation and decrease cAMP accumulation. In these cells, but not in wild type cells, haloperidol, fluphenazine, and various other antipsychotics inhibited basal [3H]thymidine incorporation in a concentration-dependent manner. In contrast, other dopamine antagonists such as nafadotride or (+)AJ 76, two D3-preferring antagonists, were without effect. The concentration-response curve of haloperidol was shifted to the right in presence of nafadotride, with a potency compatible with its nanomolar apparent affinity as neutral antagonist. Pertussis toxin treatment abolished or markedly reduced the responses to haloperidol or fluphenazine. In contrast, no significant enhancement of cAMP accumulation could be observed, under the influence of haloperidol or eticlopride. These data indicate that some dopamine antagonists behave as inverse agonists, and thus appear to inhibit an agonist-independent activity of the D3 receptor on [3H]thymidine incorporation pathway, but not on the cAMP pathway. 相似文献
14.
帕罗西汀对抑郁模型大鼠不同脑区环磷酸腺苷反应元件结合蛋白的影响 总被引:2,自引:0,他引:2
目的探讨帕罗西汀在不同用药时间对抑郁模型大鼠海马、前额叶皮质环磷酸腺苷反应元件结合蛋白(CREB)磷酸化(p-CREB)及总蛋白(t-CREB)水平的影响。方法成年雄性SpragueDawley大鼠36只,随机分为6组:对照组、抑郁模型组(以下简称模型组)、抑郁模型+用药1d组(以下简称用药1d组)、抑郁模型+用药1周组(以下简称用药1周组)、抑郁模型+用药2周组(以下简称用药2周组)和抑郁模型+用药4周组(以下简称用药4周组),每组各6只。抑郁模型的制作为强迫大鼠游泳4周,每天1次,每次15min。帕罗西汀的剂量为10m∥kg体质量,灌胃给药,时间分别为1d和1,2,4周,每天1次,于每次游泳前用药。采用Westernblot法检测各组大鼠海马及前额叶皮质的p-CREB和t-CREB水平。结果(1)模型组及用药1d、1周组大鼠海马p-CREB水平明显低于对照组(P〈0.01),用药2,4周组大鼠海马p-CREB水平与对照组的差异无统计学意义(P〉0.05);模型组及各用药组海马t-CREB水平与对照组的差异无统计学意义(P〉0.05)。(2)模型组及用药1d和1,2周组大鼠前额叶皮质p-CREB水平均明显低于对照组(P〈0.05),用药4周组与对照组的差异无统计学意义(P〉0.05)。模型组及用药1d、1周组大鼠前额叶皮质t-CREB水平与对照组的差异无统计学意义(P〉0.05),用药2,4周组大鼠前额叶皮质t-CREB水平均明显高于对照组(P〈0.05或P〈0.01)。结论慢性强迫游泳导致大鼠海马及前额叶皮质CREB活性降低,长期使用帕罗西汀可逆转此效应,提高抑郁大鼠前额叶皮质的CREB水平。 相似文献
15.
环缩酚肽抑制视网膜表达VEGF及PECAM基因和血管增生 总被引:2,自引:0,他引:2
[目的]观察两种环缩酚肽衍生物(Hep-A和Hep-B)对氧诱导的小鼠视网膜表达血管内皮生长因子(VEGF)和细胞黏附分子(PECAM;ICAM-1;VCAM-1)基因的影响及血管增生的变化.[方法]建立氧诱导的血管增殖性视网膜病变模型,12 d开始给小鼠皮下注安慰剂(第1组,n=7)、Hep-A 10 mg/kg(第2组,n=6)或者Hep-B 10 mg/kg(第3组,n=6),每天两次.5 d后取出左侧眼,分离视网膜并抽提RNA,用荧光定量PCR测出上述基因含量,并分别求出每个靶基因与标准基因S16含量的比率;右眼经心脏荧光素灌注后取眼球做视网膜平铺片,用图像分析软件定量计算视网膜新生血管的面积.[结果]视网膜中VEGF/S16的mRNA比率为:第1组(0.554±0.050),第2组(0.355±0.037),第3组(0.287±0.051);PECAM/S16为:第1组(2.050±0.249),第2组(1.228±0.153),第3组(1.027±0.210).经ANOVA分析,第2组和第3组分别与第1组比较,视网膜中VEGF基因表达分别减少36%和48.2%(P=0.001);PECAM基因表达分别减少40.1%(P<0.05)和49.9%(P<0.01);而VCAM-1和ICAM-1表达无明显差异.视网膜平片检测视网膜新生血管面积:第1组为(1.06±0.03)mm2/眼,第2组为(0.17±0.01)mm2/眼,第3组为(0.11±0.01)mm2/眼;经ANOVA分析,第2组和第3组分别与第1组比较,视网膜新生血管的面积明显减少(P<0.001).[结论]两种环缩酚肽衍生物均抑制氧诱导的小鼠视网膜表达VEGF和PECAM基因,并抑制其形成视网膜新生血管. 相似文献
16.
Masao Akagi Shunji Nishimura Kohji Yoshida Takumi Kakinuma Tatsuya Sawamura Hiroshi Munakata Chiaki Hamanishi 《Journal of orthopaedic research》2006,24(8):1782-1790
Mechanical stimulation is known to be an essential factor in the regulation of cartilage metabolism. We tested the hypothesis that expression of lectin-like oxidized low-density lipoprotein receptor-1 (LOX-1) can be modulated by cyclic tensile stretch load in chondrocytes. Cyclic loading of repeated stretch stress at 10 cycles per minute with 10 kPa of stress for 6 h induced expression of LOX-1 to 2.6 times control in cultured bovine articular chondrocytes, equivalent to the addition of 10 microg/mL oxidized low density lipoprotein (ox-LDL) (2.4 times control). Application of the cyclic load to the chondrocytes along with 10 microg/mL ox-LDL resulted in synergistically increased LOX-1 expression to 6.3 times control. Individual application of cyclic loading and 10 microg/mL ox-LDL significantly suppressed chondrocytes viability (84.6% +/- 3.4% and 80.9% +/- 3.2% of control at 24 h, respectively; n = 3; p < 0.05) and proteoglycan synthesis [81.0% +/- 7.1% and 85.7% +/- 5.2% of control at 24 h, respectively; p < 0.05 when compared with 94.6% +/- 4.6% for native-LDL (n = 3)]. Cyclic loading and 10 microg/mL ox-LDL synergistically affected cell viability and proteoglycan synthesis, which were significantly suppressed to 45.6% +/- 4.9% and 48.7% +/- 6.7% of control at 24 h, respectively (n = 3; p < 0.01 when compared with individual application of cyclic loading or 10 microg/mL ox-LDL). In this study, we demonstrated synergistic effects of cyclic tensile stretch load and ox-LDL on cell viability and proteoglycan synthesis in chondrocytes, which may be mediated through enhanced expression of LOX-1 and which has important implications in the progression of cartilage degeneration in osteoarthritis. 相似文献
17.
主要介绍了合成药厂多功能中试车间设计的有关事项,包括车间的布局、工艺条件的设计、设备的选型、供电与仪表自控、环保、消防与安全以及原料药精烘包洁净操作区的设计.设计的范围较广,参考借鉴性强. 相似文献
18.
观察7例慢性哮喘病人胸导管引流治疗前后外周血淋巴细胞内 cAMp/cGMP 值的变化。结果发现,慢性哮喘病人外周血淋巴细胞内 cAMP/cGMP 的值较正常人低(P<0.001);胸导管引流治疗后,哮喘病人外周血淋巴细胞内 cAMP/cGMP 值较治疗前升高(P<0.01)。提示,慢性哮喘病人外周血淋巴细胞功能异常、活性增强,这可能是哮喘发病的重要原因之一。胸导管引流引起的免疫抑制作用,一个重要的机理就是影响淋巴细胞内环核苷酸的代谢,而使淋巴细胞的活性降低,这可能也是胸导管引流治疗慢性哮喘的机理之一。 相似文献
19.
Intrastriatal injection of the GABAA antagonist, bicuculline, caused about a 75% decrease in the inhibitory effect of the central-type benzodiazepine (BZ) agonist, clonazepam or the indoleamine hormone, melatonin, on apomorphine-induced rotation in a 6-hydroxydopamine model of dopaminergic supersensitivity. Pretreatment with the peripheral-type BZ antagonist, PK 11195 (intrastriatally or intraperitoneally), also attenuated the antidopaminergic effect of these drugs but with much less potency than bicuculline. However, the combination of both bicuculline and PK 11195, injected directly into the striatum, completely blocked the antidopaminergic action of clonazepam or melatonin. These results indicate that the antidopaminergic action of clonazepam and melatonin in the striatum involves two distinct mechanisms: (1) a predominant GABAergic activation via the BZ/GABAA receptor complex, and (2) a secondary mechanism linked to a PK 11195- sensitive BZ receptor pathway. Recent studies indicate that PK 11195 blocks BZ-induced inhibition of the adenylyl cyclase-cyclic AMP pathway in the striatum. Since cyclic AMP has been implicated in the rotational behaviour of 6-hydroxydopamine-lesioned animals, it is possible that the antidopaminergic action of clonazepam and melatonin also involves suppression of this second messenger. All rights reserved. 相似文献
20.
The helicity of the tryptathionine moiety of the phallotoxins has been recognized by comparison with cyclic tryptathionine tripeptides. In order to investigate the influence of the configuration of the component amino acids on the conformation of the cyclic peptides, six analogue thioether tripeptides containing L- and D-alanine and L- and D-cysteine, respectively, have been synthesized. The CD spectra of the peptides are very similar to each other, showing mirror images of the CD of phalloidin and, therefore, negative helicity. The spectra of the D-cysteine containing compounds differ from the L-cysteine containing compounds by their weakly positive ellipticity values around 270 nm. The cyclization reaction of Boc-Hpi-D-Ala-D-Cys(STrt)OCH3, along with the cyclic tripeptide, afforded a cyclic hexapeptide by dimerization. The CD spectrum of the dimer is very similar to that of phalloidin, thus pointing to a positive helicity of its two tryptathionine moieties. The dimeric thioether peptide forms a rather strong complex with Cu2+ ions. 相似文献