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31.
Zhong Q. Wang Audrey D. Bell-Farrow William Sonntag William T. Cefalu 《Experimental gerontology》1997,32(6):E966-684
We report on the effect of age and chronic caloric restriction (CR) on insulin binding and glucose transporter content in both diaphragm and heart muscle membrane of young (11 months), mid-age (17 months), and old (29 month) ad libitum fed and CR Brown-Norway rats. The control animals received rat chow ad lib and CR animals were allowed 60% of ad libitum food. The CR regimen was initiated at four months of age and the animals were maintained on their respective diets until necropsy. There was no effect of age on insulin binding for either ad libitum or CR animals at each age evaluated. Caloric restriction significantly lowered insulin levels at each age studied when compared to the ad libitum-fed rats. However, CR animals were noted to have increased insulin binding (p < 0.001) compared to ad libitum-fed animals at each age for diaphragm muscle. For the heart, there appeared to be a decreased binding, particularly at higher insulin concentrations, in CR-fed animals. There was no net change in Glut-1 or Glut-4 levels for heart muscle membrane, or Glut-4 levels for diaphragm muscle membrane between ad libitum or CR animals. This data indicates that caloric restriction may have tissue-specific effects for insulin receptor binding, and that the improved insulin sensitivity in CR states is not a result of altered glucose transporter protein content. 相似文献
32.
Xinyu D. Li Esperanza Arias Ramamohana R. Jonnala Shyamala Mruthinti Jerry J. Buccafusco 《Journal of molecular neuroscience : MN》1996,27(3):325-336
The ability of nicotine to induce a cytoprotective or neuroprotective action occurs through several down-stream mechanisms.
One possibility is that the drug increases the expression of tyrosine kinase A (TrkA) nerve growth factor (NGF) receptors.
Certain β-amyloid peptides (e.g., Aβ1–42) have been shown to bind with high affinity to α7 nicotinic receptors and thus interfere
with a potentially neurotrophic influence. Treatment of differentiated PC-12 cells with nicotine produced a concentration-dependent
increase in cell-surface TrkA receptors that occurred concomitantly with cytoprotection. The effect of nicotine was blocked
by either of the α7 receptor antagonists α-bungarotoxin (α-BTX) or methyllycaconatine. The cytoprotective action of nicotine
also was inhibited by pretreatment with 10–100 nM Aβ1–42. Nicotine also was administered (four injections of 30 μg, spaced evenly over 24 h) to rats by direct injection into
a lateral cerebral ventricle. Brain TrkA expression was increased significantly in hippocampus and entorhinal cortex (up to
32% above control), with no changes found in cerebral cortex or hypothalamus. The nicotine-induced increases in TrKA expression
in hippocampus and entorhinal cortex were significantly inhibited by 10 μg α-BTX or by 10 nmol Aβ1–42. Therefore, physiologically
relevant concentrations of Aβ1–42 can prevent nicotine-induced TrkA receptor expression in brain regions containing cholinergic
neurons susceptible to the neurotoxicity associated with Alzheimer’s disease. 相似文献
33.
Summary— The regulation and role of the intracellular Ca2+ pools were studied in rat peritoneal mast cells. Cytosolic free calcium concentration ([Ca2+ ]i) was monitored in fura-2 loaded mast cells. In the presence of Ca2+ and K+, compound 48/80 induced a biphasic increase in [Ca2+ ]i composed of a fast transient phase and an apparent sustained phase. The sustained phase was partially inhibited by the addition of Mn2+ . DTPA, a cell-impermeant chelator of Mn2+ , reversed this inhibition, suggesting that a quenching of fura-2 fluorescence occurs in the extracellular medium. In the absence of extracellular Ca2+ , the transient phase, but not the sustained one, could be preserved, provided that mast cells were depolarized. The transient phase was completely abolished by thapsigargin, a microsomal Ca2+ -ATPase inhibitor. Maximum histamine release induced by either compound 48/80 or antigen was obtained in the absence of added Ca2+ only when mast cells were depolarized. These histamine releases were inhibited by low doses (< 30 nM) of thapsigargin. Thapsigargin at higher doses induced histamine release which was unaffected by changing the plasma membrane potential, but was completely dependent on extracellular Ca2+ , showing that a Ca2+ influx is required for thapsigargin-induced exocytosis. Together, these results suggest that the mobilization of Ca2+ from thapsigargin sensitive-intracellular pools induced by compound 48/80 or antigen is sufficient to trigger histamine release. The modulation of these pools by the plasma membrane potential suggest their localization is close to the plasma membrane. 相似文献
34.
烟碱对脑M胆碱能受体信息跨膜转导的调节 总被引:1,自引:1,他引:0
采用体外实验研究烟碱对大鼠脑M受体信息跨膜转导的调节作用.脑突触体以烟碱1.0μmol·L-1预处理后,[3H]l-二苯羟乙酸奎宁酯与M受体结合及解离动力学过程减慢.在溶脱的大脑皮层M受体与G蛋白复合体上,烟碱1.0μmol·L-1可减慢[35S]-腺苷5'-[γ-硫]三磷酸与G蛋白的结合,并增强M受体与G蛋白之间的偶联关系.烟碱0.1~1000μmol·L-1既不影响纹状体腺苷酸环化酶的基础活性,也不影响氟化钠激活腺苷酸环化酶的作用.烟碱0.1~30μmol·L-1浓度依赖性地提高脑细胞内Ca2+浓度.据此提出烟碱对脑M受体信息跨膜转导系统有多点调节作用. 相似文献
35.
Juan F López-Giménez Laurence H Tecott José M Palacios Guadalupe Mengod M Teresa Vilaró 《Journal of neuroscience research》2002,67(1):69-85
Quantitative receptor autoradiography was used to study possible alterations of the densities of multiple serotonin (5-HT) receptor subtypes and of serotonin transporter in the brain of 5-HT(2C) receptor knockout mice. The radioligands employed were [(3)H]citalopram, [(3)H]WAY100,635, [(3)H]8-OH-DPAT, [(3)H]GR125743, [(3)H]sumatriptan, [(3)H]MDL100,907, [(125)I](+/-)DOI, [(3)H]mesulergine, [(3)H]5-HT, [(3)H]GR113808, and [(3)H]5-CT. As expected, radioligands that label 5-HT(2C) receptors showed a complete absence of labeling in mutant mice choroid plexus and significantly reduced densities in other brain regions expressing 5-HT(2C) receptors. With the rest of the radioligands, no significant alterations in the densities of labeled sites were found in any brain region. In situ hybridization showed no changes in 5-HT(2A) receptor and serotonin transporter mRNA levels, whereas 5-HT(2C) receptor mRNA levels were reduced in certain brain regions. The present results indicate that the mouse serotonergic system does not exhibit compensatory up- or down-regulation of the majority of its components (serotonin transporter and most 5-HT receptor subtypes) in response to the absence of 5-HT(2C) receptors. 相似文献
36.
本文报告口服Sumatriptan 100mg对偏头痛急性发作119例次的治疗结果。治疗后4h内显效91例次(76.5%),好转16例次(13.4%),无效12例次(10.1%),总有效率为89.9%。对偏头痛伴随症状恶心、呕吐和畏光、畏声的缓解率分别为94.2%、96%和94.3%。 相似文献
37.
用单侧输尿管梗阻的方法诱导小鼠肾间质纤维化,并从中成功地培养出了成纤维细胞。对成纤维细胞血管紧张素Ⅱ1A(AT1A)受体的表达与细胞增殖和分泌细胞外基质的关系进行了研究。结果发现,从肾间质纤维化组织中培养出的成纤维细胞,细胞增殖和产生纤维连接蛋白及层粘连蛋白的能力明显高于从正常肾间质中培养的成纤维细胞。在单侧输尿管梗阻小鼠的血浆和肾组织中血管紧张素Ⅱ的活性显著升高。从肾间质纤维化组织中培养出的成纤维细胞,AT1A受体的表达在蛋白质和分子水平上均有明显增高。表明,在肾间质纤维化过程中肾素-血管紧张素系统被激活,对刺激成纤维细胞增殖和产生细胞外基质起着重要作用。 相似文献
38.
Kupffer cell depletion in vivo results in preferential elimination of IgG aggregates and immune complexes via specific Fc receptors on rat liver endothelial cells. 总被引:2,自引:1,他引:1 下载免费PDF全文
W M Bogers R K Stad D J Janssen N van Rooijen L A van Es M R Daha 《Clinical and experimental immunology》1991,86(2):328-333
In the present study we have investigated the clearance kinetics and tissue distribution of monomeric (m) IgG and soluble aggregates of IgG (AIgG) and immune complexes (IC) in normal and Kupffer cell (KC) depleted rats. In normal rats, clearance of mIgG occurred in a biphasic manner with a first half-life (T1/2) (T1) of 36.3 +/- 6.3 min and a second T1/2 (T2) of 168.4 +/- 4.7 min. AIgG composed of 20-27 IgG molecules per aggregate were cleared significantly faster than mIgG with a T1 of 2.5 +/- 0.1 min and a T2 of 32.5 +/- 5.6 min. KC depletion did not have a significant effect on the clearance rate of mIgG (T1: 33.4 +/- 8.9 min; T2; 159.5 +/- 12.5 min), while clearance of AIgG was delayed significantly with T1 4.8 +/- 0.7 min and T2 41.2 +/- 3.2 min. Eight minutes after injection, 77% of AIgG was found in the liver in normal rats while 62% was found in the liver of KC-depleted rats. Double immunofluorescence studies indicated that AIgG in the liver was associated with KC and endothelial cells (EC) in normal rats. In KC-depleted rats, AIgG was strongly associated with EC. A similar staining pattern was observed when IgG-immune IC were administered. The clearance of AIgG in KC-depleted rats was inhibited fully by pre-administration of high concentrations of IgG but not by pretreatment with IgA. asialofetuin (ASFe) or ovalbumin (OVA). Aggregated F(ab')2IgG was cleared with a comparable rate to mIgG from the circulation, again suggesting Fc gamma receptor-mediated elimination of AIgG by EC. There was a reduced degradation of AIgG in rats depleted of KC as compared with normal rats. These data suggest binding and degradation of AIgG by EC in vivo. 相似文献
39.
Geraldo F. Busatto Lyn S. Pilowsky Durval C. Costa John Mertehs Dirk Terriere Peter J. Ell Rachel Mulligan Michael J. Travis Josée E. Leysen Dominic Lui Sveto Gacinovic Wendy Waddington Anne Lingford-Hughes Robert W. Kerwin 《European journal of nuclear medicine and molecular imaging》1997,24(2):119-124
The mapping of 5-HT2 receptors in the brain using functional imaging techniques has been limited by a relative lack of selective radioligands.
Iodine-123 labelled 4-amino-N-[1-[3-(4-fluorophenoxy)propyl]-4-methyl-4-piperidinyl]-5-iodo-2-methoxybenzamide (123I-5-I-R91150 or123I-R93274) is a new ligand for single-photon emission tomography (SPET), with high affinity and selectivity for 5-HT2A receptors. This study reports on preliminary123I-5-I-R91150 SPET, wholebody and blood distribution findings in five healthy human volunteers. Maximal brain uptake was approximately
2% of total body counts at 180 min post injection (p.i.). Dynamic SPET sequences were acquired with the brain-dedicated, single-slice
multi-detector system SEM-810 over 200 min p.i. Early peak uptake (at 5 min p.i.) was seen in the cerebellum, a region free
from 5HT2A receptors. In contrast, radioligand binding in the frontal cortex increased steadily over time, up to a peak at approximately
100–120 min p.i. Frontal cortex-cerebellum activity ratios reached values of 1.4, and remained stable from approximately 100
min p.i. onwards. Multi-slice SPET sequences showed a pattern of regional variation of binding compatible with the autoradiographic
data on the distribution of 5-HT2A receptors in (cerebral cortex>striatum>cerebellum). These findings suggest that123I-5-I-R91150 may be used for the imaging of 5-HT2A receptors in the living human brain with SPET. 相似文献
40.
Glutamate is the primary excitatory amino acid in the mammalian central nervous system. Normal excitation of glutamate receptors initiates the stimulation of phospholipases and lipases with the generation of second messengers that are necessary for normal cell function. The overstimulation of glutamate receptors can initiate a cascade of biochemical events including stimulation of membrane phospholipid turnover, excessive calcium entry, abnormal phosphorylation, and proteolysis. These events may be responsible for neuronal injury and degeneration found in Alzheimer disease, ischemia, spinal cord trauma, epilepsy, and Huntington disease. 相似文献