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101.
应用鸡卵清蛋白致敏和刺激小鼠复制过敏性气道炎症反应模型研究血小板激活因子选择性拮抗剂YM-264对抗原引起气道嗜酸性粒细胞(EOS)浸润的影响。结果发现,正常小鼠支气管肺泡灌洗液(BALF)中未见到EOS;致敏小鼠给予抗原多次反复吸入刺激后,BALF中EOS急剧增多。在YM-264治疗各组中,YM-264的不同剂量分别导致EOS数下降27.0%、48.2%及67.9%。还发现YM-264抑制EOS对气道的浸润伴随着白细胞介素(IL)-5水平的明显下降。提示YM-264通过抑制IL-5的产生从而抑制了EOS在气道的聚集。 相似文献
102.
Correlation between 5-HT7 receptor affinity and protection against sound-induced seizures in DBA/2J mice 总被引:2,自引:0,他引:2
Anne Bourson Véronique Kapps Catherine Zwingelstein Alain Rudler Frank G. Boess A. J. Sleight 《Naunyn-Schmiedeberg's archives of pharmacology》1997,356(6):820-826
Audiogenic seizures can be induced in DBA/2J mice following intense auditory stimulation. A number of neurotransmitters, including
5-hydroxytryptamine (5-HT), are believed to be involved in mediating this effect since it has been shown previously that depletion
of 5-HT or blockade of 5-HT receptors protects DBA/2J mice from these audiogenic seizures. The present study was undertaken
to determine whether antagonism of the newly identified 5-HT7 receptor may protect DBA/2J mice from audiogenic seizures by attempting to correlate in vivo potency of compounds with their
affinity at the 5-HT7 receptor. All compounds used in the correlation were shown to be antagonists at the 5-HT7 receptor and a statistically significant correlation was observed between 5-HT7 affinity and doses for half-maximal response (ED50) for protection of DBA/2J mice from sound-induced seizures (r = 0.80; P < 0.05). No significant correlation was observed between in vivo activity and affinity at either 5-HT1A, 5-HT2A or 5-HT2C receptors. It is also unlikely that interactions between the 5-ht5 receptor will protect DBA/2J mice from audiogenic seizures since metergoline and mesulergine which are both active in this
in vivo model have no affinity for the 5-ht5 receptor. There are similarities between the pharmacology of the 5-HT7 receptor and that of the 5-HT1A receptor, however the correlation between the in vivo potency in DBA/2J mice and 5-HT1A affinity was not significant. Furthermore, the 5-HT1A receptor antagonist WAY 100135 did not protect DBA/2J mice from audiogenic seizures at doses that antagonise 5-HT1A receptor-mediated effects in mice. These data suggest that antagonism of 5-HT7 receptors may protect against audiogenic seizures in DBA/2J mice although a definitive conclusion must await studies with
selective 5-HT7 antagonists.
Received: 20 March 1997 / Accepted: 10 August 1997 相似文献
103.
John F. Scrymgeour-Wedderburn Carolyn A. Reith Keith T. Sillar 《The European journal of neuroscience》1997,9(7):1473-1482
The development of intrinsic, N-methyl-D-aspartate (NMDA) receptor-mediated voltage oscillations and their dependence on co-activation of 5-hydroxytryptamine (5HT) receptors was explored in motor neurons of late embryonic and early larval Xenopus laevis. Under tetrodotoxin, 100 μM NMDA elicited a membrane depolarization of around 20 mV, but did not lead to voltage oscillations. However, following the addition of 2–5 μM 5HT, oscillations were observed in 12% of embryonic and 70% of larval motor neurons. The voltage oscillations depended upon co-activation of NMDA and 5HT receptors since they were curtailed by selectively blocking NMDA receptors with D-2-amino-5-phosphonovaleric acid (APV) or by excluding Mg2+ from the experimental saline. 5HT applied in the absence of NMDA also failed to elicit oscillations. Oscillations could be induced by the non-selective 5HT1a receptor agonist, 5-carboxamidotryptamine (5CT) and both 5HT- and 5CT-induced oscillations were abolished by pindobind-5HT1, a selective 5HT1a receptor antagonist. To test whether 5HT enables voltage oscillations by modulating the voltage-dependent block of NMDA channels by Mg2+, membrane conductance was monitored under tetrodotoxin. Although 5HT caused membrane hyperpolarization of 4–8 mV, there was little detectable change in conductance. NMDA application caused an approximate 20 mV depolarization and an ‘apparent’ decrease in conductance, presumably due to the conductance pulse bringing the membrane into a voltage region where Mg2+ blocks the NMDA ionophore. 5HT further decreased conductance, which we propose is due to its enhancement of the voltage-dependent Mg2+ block. When the membrane potential was depolarized by ~20 mV via depolarizing current injection (to mimic the NMDA-induced depolarization), 5HT increased rather than decreased membrane conductance. Furthermore, 5HT did not affect the increase in membrane conductance following NMDA applications in zero Mg2+ saline. The results suggest that intrinsic, NMDA receptor-mediated voltage oscillations develop in a brief period after hatching, and that they depend upon the co-activation of 5HT and NMDA receptors. The enabling function of 5HT may involve the facilitation of the voltage-dependent block of the NMDA ionophore by Mg2+ through activation of receptors with 5HT1a-like pharmacology. 相似文献
104.
Kenichiro Mikawa Hiroaki Kume Kenzo Takagi 《Clinical and experimental pharmacology & physiology》1997,24(2):175-181
1. In order to examine the mechanisms of cGMP-induced relaxation in airway smooth muscle, the effects of atrial natriuretic peptide (ANP) and 8-brom cGMP on muscle tone were studied by measuring isometric tension, while the effects on cytosolic Ca2+ concentrations were studied by measuring the spectra of fura-2 loaded in guinea-pig tracheal strips. 2. Atrial natriuretic peptide and 8-brom cGMP caused a concentration-dependent inhibition of spontaneous tone in the guinea-pig trachea. The relaxant effects of these agents on spontaneous tone were markedly suppressed in the presence of iberiotoxin (IbTX), a selective inhibitor of large-conductance Ca2+-activated K+ (BKca) channels. Iberiotoxin (30 nmol/L) markedly affected the maximal effect induced by ANP and 8-brom cGMP and augmented EC70 values for ANP and EC50values for 8-brom cGMP approximately 27- and 17-fold, respectively. The inhibitory effects of IbTX on relaxation induced by these agents were diminished in the presence of 1 μmol/L nifedipine, an antagonist of voltage-operated Ca2+channels (VOCC). 3. The inhibitory action of ANP and 8-brom cGMP on spontaneous tone was not affected by the presence of 10 μmol/L glibenclamide, an inhibitor of ATP-sensitive K+ channels, and 100 nmol/L apamin, an inhibitor of small-conductance Ca2+-activated K+ channels. When these agents were applied to tissues precontracted by high (40mmol/L) K+, the relaxant effects of these agents markedly diminished. 4. The extracellular Ca2+-dependent contraction was inhibited in the presence of 0.3 μmoI/L ANP or 0.1 mmol/L 8-brom cGMP. Concentration—response curves to extracellular Ca2+ (0.03—2.4 mmol/L) were markedly diminished by exposure to these agents. The maximal effect induced by extracellular Ca2+ was affected by these agents. 5. Atrial natriuretic peptide caused an inhibition of spontaneous tone accompanied by a reduction in the intracellular Ca2+ concentration. In the presence of IbTX, the elimination of both muscle tone and cytosolic Ca2+ by ANP was suppressed. 6. We conclude that ANP and 8-brom cGMP activate BKca channels and that the inhibition of Ca2+ influx through VOCC, mediated by BKca channel activation, may be involved in cGMP-dependent bronchodilation. 相似文献
105.
Stanislw Ryng Zdzislw Machn Zbigniew Wieczorek Michal Zimecki Tadeusz Glowiak 《Archiv der Pharmazie》1997,330(11):319-326
A series of 5-aminomethinimino-3-methyl-4-isoxazolecarboxylic acid phenylamides 4 has been prepared by condensation of 5-amino-3-methyl-4-isoxazolecarboxylic acid phenylamides 1 with trichloroacetic aldehyde. Alcoholysis of trichloro derivatives 2 gave 5-alkoxymethine derivatives 3 which, on reaction with an appropriate amine, formed the corresponding compounds 4 . The compounds obtained were evaluated for their immunological activity. The properties of three compounds, described in this report, permitted inhibition of the immune response in all possible ways: diminishing both types of immune response ( 4d ), humoral immune response ( 4a ), or cellular immune response ( 4c ). Preparation 4d is comparable in its effectiveness to CsA, so it may be potentially used as an agent for prolongation of the function of transplanted organs. Two other compounds may potentially be used in cases where only one type the immune response is required for combating pathogen invasion. 相似文献
106.
107.
Alan T. Villavicencio MD Lloyd A. Hey MD Dhavalkumar Patel MD PhD Peter Bressler MD 《The Journal of allergy and clinical immunology》1997,100(6):853-854
J Allergy Clin Immunol 1997;100:853-4. 相似文献
108.
Hypereosinophilic syndrome in Hodgkin's disease with increased granulocyte-macrophage colony-stimulating factor 总被引:2,自引:0,他引:2
We report a patient with eosinophilia accompanied by Hodgkin's disease who showed remarkable increase in granulocyte-macrophage colony-stimulating factor (GM-CSF) in plasma but no increase in interleukin-5 (IL-5). The plasma GM-CSF level normalized as eosinophilia and lymphadenopathy disappeared after chemotherapy. Immunohistochemical study with immunoperoxidase staining technique showed a positive stain in lymph node cells by monoclonal anti-GM-CSF antibody. Eosinophilia is often accompanied by Hodgkin's disease, and several cases have been reported to show high levels of plasma IL-5. To our knowledge, this is the first report to show a high level of plasma GM-CSF in Hodgkin's disease with eosinophilia. 相似文献
109.
以环己酮为起始原料,经与苯肼缩合、氧化、Mannich 反应制得1,2,3,9-四氢-3-二甲胺基甲基-4H-咔唑-4-酮盐酸盐(5),后者再与2-甲基咪唑缩合、甲基化合成翁丹西隆,总收率为10.4%。 相似文献
110.
Z. Lackovi M. Jakup
evi A. Bunarevi I. Damjanov M. Relja I. Kostovi 《Brain research》1988,443(1-2):199-203
The content of serotonin (5-HT), 5-hydroxyindoleacetic acid (5-HIAA) and norepinephrine (NE) was analysed in 71 human spinal cords obtained post-mortem. The highest content of 5-HT, 5-HIAA and NE was found in the lumbar enlargement of the spinal cord. 5-HT and 5-HIAA content increased from fetal to adult spinal cord whereas the content of NE decreased. Characteristic segmental distribution of measured monoamines was present in adult spinal cord only. In two patients spinal cord lesion led to the reduction in spinal cord content of 5-HT, 5-HIAA and NE and loss of characteristic segmental distribution of these substances. These results are in general agreement with observations on spinal cord of different animal species. 相似文献