检索结果-内蒙古大学图书馆

ATP-sensitive potassium channels in capillaries isolated from guinea-pig heart

JOURNAL OF PHYSIOLOGY-LONDON 2000年第2期525卷 307-317页

作者： Schnitzler, MMY Derst, C Daut, J Preisig-Müller, R Univ Marburg Inst Normale & Pathol Physiol D-35037 Marburg Germany

1. The full-length cDNAs of two different alpha-subunits (Kir6.1 and Kir6.2) and partial cDNAs of three different beta-subunits (SUR1, SUR2A and SUR2B) of ATP-sensitive potassium (K-ATP) channels of the guinea-pig (gp) were obtained by screening a cDNA library from the ventricle of guinea-pig heart. 2. Cell-specific reverse-transcriptase PCR with gene-specific intron-spanning primers showed that gpKir6.1, gpKir6.2 and gpSUR2B were expressed in a purified fraction of capillary endothelial cells. In cardiomyocytes, gpKir6.1, gpKir6.2, gpSUR1. and gpSUR2A were detected. 3. Patch-clamp measurements were carried out in isolated capillary fragments consisting of 3-15 endothelial cells. The membrane capacitance measured in the whole-cell mode was 19.9 +/- 1.0 pF and was independent of the length of the capillary fragment, which suggests that the endothelial cells were not electrically coupled under our experimental conditions. 4. The perforated-patch technique was used to measure the steady-state current-voltage relation of capillary endothelial cells. Application of K+ channel openers (rilmakalim or diazoxide) or metabolic inhibition (250 mu M 2,4-dinitrophenol plus 10 mM deoxyglucose) induced a current that reversed near the calculated K+ equilibrium potential. 5. Rilmakalim (1 mu M), diazoxide (300 mu M) and metabolic inhibition increased the slope conductance measured at -55 mV by a factor of 9.0 (+/- 1.8), 2 5 (+/- 0.2) and 3.9 (+/- 1.7), respectively. The effects were reversed by glibenclamide (1 mu M). 6. Our results suggest that capillary endothelial cells from guinea-pig heart express K-ATP channels composed of SUR2B and Kir6.1 and/or Kir6.2 subunits. The hyperpolarization elicited by the opening of K-ATP channels may lead to an increase in free cytosolic Ca2+, and thus modulate the synthesis of NO and the permeability of the capillary wall.

关键词：腺苷三磷酸/代谢抗代谢药/药理学碱基序列毛细血管/代谢克隆分子 DNA引物/遗传学 DNA 互补/遗传学内皮血管/代谢膜电位/药物作用心肌/代谢膜片钳术钾通道/化学钾通道/遗传学钾通道/代谢 RNA 信使/遗传学 RNA 信使/代谢组织分布动物豚鼠

来源：评论

学校读者我要写书评

暂无评论

Mitochondrial regulation of the cytosolic Ca²⁺ concentration and the InsP₃-sensitive Ca²⁺ store in guinea-pig colonic smooth muscle

引用

JOURNAL OF PHYSIOLOGY-LONDON 1999年第1期516卷 149-161页

作者： McCarron, JG Muir, TC Univ Glasgow Inst Biomed & Life Sci Neurosci & Biomed Syst Glasgow G12 8QQ Lanark Scotland

1. Mitochondrial regulation of the cytosolic Ca2+ concentration ([Ca2+](c)) in guinea-pig single colonic myocytes has been examined, using whole-cell recording, flash photolysis of caged InsP(3) and microfluorimetry. 2. Depolarization increased [Ca2+](c) and triggered contraction. Resting [Ca2+](c) was virtually restored some 4 s after the end of depolarization, a time when the muscle had shortened to 50% of its fully relaxed length. The muscle then slowly relaxed (t(1/2) = 17 s). 3. The decline in the Ca2+ transient was monophasic but often undershot or overshot resting levels, depending on resting [Ca2+](c). The extent of the overshoot or undershoot increased when increasmg peak [Ca2+](c). 4. Carbonyl cyanide m-chlorophenyl hydrazone (CCCP;5 mu M), which dissipates the mitochondrial proton electrochemical gradient and therefore prevents mitochondrial Ca2+ accumulation, slowed Ca2+ removal at high (> 300 nM) but not at lower [Ca2+](c) and abolished [Ca2+](c) overshoots. Oligomycin B (5 mu M), which prevents mitchondrial ATP production, affected neither the rate of decline nor the magnitude of the overshoot. 5. During depolarization, the global rhod-2 signal (which represents the mitochondrial matrix Ca2+ concentration, [Ca2+](m)) rose slowly in a CCCP-sensitive manner during and for about 3 s after depolarization had ended. [Ca2+](m) then slowly decreased over tens of seconds. 6. Inhibition of sarcoplasmic reticulum Ca2+ uptake with thapsigargin (100 nM) reduced the undershoot and increased the overshoot. 7. Flash photolysis of caged InsP(3) (20 mu M) evoked reproducible increases in [Ca2+](c). CCCP (5 mu M) reduced the magnitude of the [Ca2+](c) transients evoked by flash photolysis of caged InsP(3). Oligomycin B (5 mu M) did not reduce the inhibition of the InsP(3)-induced Ca2+ transient by CCCP thus minimizing the possibility that CCCP lowered ATP levels by reversing the mitochondrial ATP synthase and so reducing SR Ca2+ refilling. 8. While CCCP reduced the magn

关键词：腺苷三磷酸酶类/药理学抗代谢药/药理学钙/代谢碳酰氰化物间-氯苯基腙/药理学结肠/药物作用结肠/代谢结肠/超微结构胞质溶胶/药物作用胞质溶胶/代谢胞质溶胶/超微结构酶抑制剂/药理学荧光染料/诊断应用杂环化合物 3环肌醇1 4 5-三磷酸/药理学离子载体/药理学膜电位/生理学线粒体肌/代谢肌平滑/药物作用肌平滑/代谢肌平滑/超微结构寡霉素类/药理学膜片钳术毒胡萝卜内酯/药理学动物豚鼠男(雄)性

来源：评论

学校读者我要写书评

暂无评论

Suppression of replication of multidrug-resistant HIV type 1 variants by combinations of thymidylate synthase inhibitors with zidovudine or stavudine

引用

MOLECULAR PHARMACOLOGY 1999年第3期55卷 535-540页

作者： Gao, WY Johns, DG Tanaka, M Mitsuya, H NCI Expt Retrovirol Sect Med Branch Div Clin SciNIH Bethesda MD 20892 USA NCI Med Chem Lab Div Basic Sci NIH Bethesda MD 20892 USA

The replication of recombinant multidrug-resistant HIV-I clones modeled on clinically derived resistant HIV-I strains from patients receiving long-term combination therapy with zidovudine (AZT) plus 2',3'-dideoxycytidine was found to regain sensitivity to AZT and stavudine (D4T) as a consequence of a pharmacologically induced decrease in de novo dTMP synthesis. The host-cell system used was phytohemagglutinin-stimulated peripheral blood mononuclear cells;dTMP and dTTP depletion were induced by single exposures to a low level of the thymidylate synthase inhibitor 5-fluorouracil (5-FU) or its deoxynucleoside, 2'-deoxy-5-fluorouridine. The host-cell response to the latter was biphasic: a very rapid decrease in the rate of de novo dTMP formation and, consequently, in intracellular dTTP pools, followed by slower recovery in both indices over 3 to 24 h. With the additional presence of AZT or D4T, however, replication of the multidrug-resistant HIV-I strains remained inhibited, indicating dependence of HIV DNA chain termination by AZT-5'-monophosphate or 2',3'-didehydro-2',3'-dideoxythymidine-5'-monphosphate in these resistant strains on simultaneous inhibition of host-cell de novo synthesis of thymidine nucleotides. No effect on viability of control (uninfected) phytohemagglutinin-stimulated/peripheral blood mononuclear cells was noted on 6-day exposures to 5-FU or 2'-deoxy-5-fluorouridine alone or in combination with AZT or D4T, even at drug levels severalfold higher than those used in the viral inhibition studies. These studies may provide useful information for the potential clinical use of AZT/5-FU or D4T/5-FU combinations for the prevention or reversal of multidrug resistance associated with long-term dideoxynucleoside combination therapy.

关键词：抗HIV药/药理学抗代谢药/药理学药物相互作用抗药性微生物抗药性多药氟尿苷/药理学氟尿嘧啶/药理学 HIV-1/药物作用 HIV-1/分离和提纯突变逆转录酶抑制剂/药理学司他夫定/药理学胸苷酸合酶/拮抗剂和抑制剂胸腺嘧啶核苷酸类/代谢病毒复制/药物作用齐多夫定/药理学人类

来源：评论

学校读者我要写书评

暂无评论

EFFECT OF METABOLIC-INHIBITORS ON BONE LIPID-SYNTHESIS FROM RADIOACTIVE BASES

引用

JOURNAL OF DENTAL RESEARCH 1975年第5期54卷 1009-1014页

作者： DIRKSEN, TR SCHUSTER, GS MCKINNEY, R BUSTOS, SE MED COLL GEORGIA SCH MEDDEPT PATHOLAUGUSTAGA 30902 MED COLL GEORGIA SCH DENTDEPT ORAL BIOLAUGUSTAGA 30902 MED COLL GEORGIA SCH DENTDEPT ORAL PATHOLAUGUSTAGA 30902 MED COLL GEORGIA SCH MEDDEPT CELL & MOLEC BIOLAUGUSTAGA 30902

Iodoacetate at 10 -3 M and 10-4 M concentrations was found to strongly inhibit incorporation of both 14C-choline and 3H-inositol into phospholipids of calvaria from newborn rats; it had somewhat less effect on ethanol... 详细信息

Iodoacetate at 10^-3 M and 10^-4 M concentrations was found to strongly inhibit incorporation of both ¹⁴C-choline and ³H-inositol into phospholipids of calvaria from newborn rats; it had somewhat less effect on ethanolamine incorporation and almost no effect on serine incorporation. Similar though less dramatic results were observed with cyanide or dinitrophenol at similar concentrations.

关键词：动物新生抗代谢药/药理学骨和骨组织/代谢碳放射性同位素胆碱/代谢氰化物/药理学二硝基酚类/药理学乙醇胺类/代谢肌醇/代谢碘醋酸盐类/药理学脂类/生物合成磷脂酰丝氨酸类/生物合成丝氨酸/代谢氚动物大鼠

来源：评论

学校读者我要写书评

暂无评论

GENETIC EXPRESSION OF ARYL-HYDROCARBON HYDROXYLASE-ACTIVITY IN MOUSE - DISTINCTION BETWEEN RESPONSIVE-HOMOZYGOTE AND RESPONSIVE-HETEROZYGOTE AT AH-LOCUS

引用

ARCHIVES OF BIOCHEMISTRY AND BIOPHYSICS 1975年第2期166卷 559-564页

作者： NIWA, A KUMAKI, K NEBERT, DW POLAND, AP NICHHD NEONATAL & PEDIAT MED BRANCHBETHESDAMD 20014 UNIV ROCHESTER SCH MED & DENTDEPT PHARMACOL & TOXICOLROCHESTERNY 14642

β-Napththoflavone administration induces certain monooxygenase activities, such as aryl hydrocarbon (benzo[a ]pyrene) hydroxylase, and cytochrome P 1 -450 formation in the “responsive” C57BL/6 and C3H/He inbred mouse strains, whereas these changes are absent or relatively small in the so-called nonresponsive DBA 2 inbred strain. Dose-response curves—with the use of large numbers of animals of the same age and sex and with either β-naphthoflavone or the much more potent 2,3,7,8-tetrachlorodibenzo-p -dioxin as inducer—reveal a small, but statistically significant, difference in the hydroxylase induction between the C 57 BL 6 J homozygote and the (C 57 BL 6 J )(DBA 2 J )F1 heterozygote in liver, kidney, bowel, and lung. The (C3H/HeJ)(DBA 2 J )F1 heterozygote displays additive inheritance in each of these same tissues.

关键词：抗代谢药/药理学染色体图交叉遗传二恶烷类/药理学酶诱导/药物作用杂合子纯合子肠/酶学肾/酶学肝/酶学肺/酶学甲基胆蒽/药理学小鼠近交系混合功能氧化酶类/代谢动物小鼠

来源：评论

学校读者我要写书评

暂无评论

The increased sensitivity of neurons with elevated glucocerebroside to neurotoxic agents can be reversed by imiglucerase

引用

JOURNAL OF INHERITED METABOLIC DISEASE 2000年第2期23卷 175-184页

作者： Pelled, D Shogomori, H Futerman, AH Weizmann Inst Sci Dept Biol Chem IL-76100 Rehovot Israel

We have recently demonstrated that incubation of cultured rat hippocampal neurons with conduritol beta-epoxide (CBE), an inhibitor of glucocerebrosidase, the enzyme defective in Gaucher disease, results in changes in intracellular morphology and in functional calcium stores. Changes in levels of functional calcium stores are directly related to neuronal cell death. We now show that neurons incubated with either CBE or a non-hydrolysable analogue of GlcCer (glucosylthioceramide), are more sensitive to the toxic effects of high concentrations of glutamate and of a variety of metabolic inhibitors. A linear relationship exists between level of accumulation of GlcCer and the extent of neuronal cell death. The deleterious effects of elevated GlcCer levels can be completely reversed by addition of human glucocerebrosidase (imiglucerase) to the culture medium. Imiglucerase is internalized to lysosomes, where it presumably degrades excess GlcCer. This suggests that the limited success of enzyme replacement therapy in neuronopathic forms of Gaucher disease is not due to lack of efficacy of glucocerebroside in degrading GlcCer in neurons of the central nervous system, and adds impetus to attempts to develop ways to efficiently deliver glucocerebrosidase to the brains of neurologically compromised Gaucher disease patients.

关键词：抗代谢药/药理学羧酸类/药理学细胞死亡细胞培养的酶抑制剂/毒性伏马菌素类戈谢病/酶学葡糖苷酰鞘氨醇酶/拮抗剂和抑制剂葡糖苷酰鞘氨醇酶/药理学葡糖苷酰鞘氨醇类/代谢海马/细胞学海马/药物作用肌醇/类似物和衍生物肌醇/毒性神经元/药物作用神经元/代谢神经毒素类/毒性大鼠 Wistar 重组蛋白质类/药理学动物大鼠

来源：评论

学校读者我要写书评

暂无评论

Mechanisms of hypoxic vasodilatation of isolated rat mesenteric arteries: a comparison with metabolic inhibition

引用

JOURNAL OF PHYSIOLOGY-LONDON 1999年第1期516卷 249-259页

作者： Otter, D Austin, C Manchester Royal Infirm Dept Med Manchester M13 9WL Lancs England

1. Hypoxia (P-O2 < 5 mm Hg) decreased vessel tone in isolated rat mesenteric arteries precontracted with either high [K+] or the thromboxane analogue U46619. This response was not altered by N-nitro-L-arginine (L-NA) and indomethacin. 2. Simultaneous measurement of pH(i) and tension showed that the decrease in vessel tone was accompanied by an intracellular acidification. Similar reductions in tone and pH(i) were observed with the metabolic inhibitors 2,4-dinitrophenol (DNP) and sodium azide. 3. The presence of the lactate transport inhibitor alpha-cyano-4-hydroxy-cinnamic acid (CHC) increased the magnitude of the acidification and resulted in a significantly faster reduction in tone in response to hypoxia. Addition of CHC to normoxic tissues caused both a vasodilatation and a reduction of pH(i). 4. A decrease in pH(i) induced on washout of ammonium chloride (NH4Cl) resulted in an increase in tone. 5. Relaxation to hypoxia or metabolic inhibition was unaffected when the change in pH(i) was neutralized by addition of the weak base trimethylamine (TMA). 6. It is concluded that severe hypoxia decreases tone in isolated rat mesenteric arteries by a mechanism which is independent of nitric oxide and prostaglandins. Both severe hypoxia and metabolic inhibition reduced pH(i), although this does not appear to be contributing to the changes in tone observed.

关键词： 15-羟基-11α 9α-(环氧亚甲基)前列腺-5 13-二烯酸/药理学 2 4-二硝基苯酚/药理学氯化铵/药理学缺氧/病理生理学抗代谢药/药理学氢离子浓度肠系膜动脉/药物作用肠系膜动脉/病理生理学甲胺类/药理学肌收缩/药物作用肌松弛/药物作用一氧化氮/生理学钾/药理学大鼠 Wistar 解偶联药/药理学血管舒张/药物作用血管舒张/生理学动物男(雄)性大鼠

来源：评论

学校读者我要写书评

暂无评论

Hematopoietic stem cell quiescence maintained by p21^cip1/waf1

引用

SCIENCE 2000年第5459期287卷 1804-1808页

作者： Cheng, T Rodrigues, N Shen, HM Yang, YG Dombkowski, D Sykes, M Scadden, DT Harvard Univ Massachusetts Gen Hosp Sch Med Transplantat Biol Res Ctr Boston MA 02129 USA Massachusetts Gen Hosp Ctr Canc AIDS Res Ctr Boston MA USA

Relative quiescence is a defining characteristic of hematopoietic stem cells, while their progeny have dramatic proliferative ability and inexorably move toward terminal differentiation. The quiescence of stem cells has been conjectured to be of critical biologic importance in protecting the stem cell compartment, which we directly assessed using mice engineered to be deficient in the G(1) checkpoint regulator, cyclin-dependent kinase inhibitor, p21(cip1/waf1) (p21). In the absence of p21, hematopoietic stem cell proliferation and absolute number were increased under normal homeostatic conditions. Exposing the animals to cell cycle-specific myelotoxic injury resulted in premature death due to hematopoietic cell depletion. Further, self-renewal of primitive cells was impaired in serially transplanted bone marrow from p21(-/-) mice, leading to hematopoietic failure. Therefore, p21 is the molecular switch governing the entry of stem cells into the cell cycle, and in its absence, increased cell cycling leads to stem cell exhaustion. Under conditions of stress, restricted cell cycling is crucial to prevent premature stem cell depletion and hematopoietic death.

关键词：抗代谢药/药理学血细胞计数骨髓移植细胞计数细胞周期细胞死亡细胞分化细胞分裂共同培养技术集落形成单位测定周期素依赖激酶抑制剂p21 细胞周期蛋白类/遗传学细胞周期蛋白类/生理学氟尿嘧啶/药理学血细胞生成造血干细胞/细胞学造血干细胞/药物作用造血干细胞/生理学内环境稳定小鼠近交系动物女(雌)性男(雄)性小鼠

来源：评论

学校读者我要写书评

暂无评论

2-deoxyglucose-induced long-term potentiation of monosynaptic IPSPs in CA1 hippocampal neurons

引用

JOURNAL OF NEUROPHYSIOLOGY 2000年第2期83卷 879-887页

作者： Krnjevic, K Zhao, YT McGill Univ Anaesthesia Res Dept Montreal PQ H3G 1Y6 Canada

In previous experiments on excitatory synaptic transmission in CA1, temporary (10-20 min) replacement of glucose with 10 mM 2-deoxyglucose (2-DG) consistently caused a marked and very sustained potentiation (2-DG LTP). To find out whether 2-DG has a similar effect on inhibitory synapses, we recorded pharmacologically isolated mononosynaptic inhibitory postsynaptic potentials (IPSPs;under current clamp) and inhibitory postsynaptic currents (IPSCs;under voltage clamp);2-DG was applied both in the presence and the absence of antagonists of N-methyl-D-aspartate (NMDA). In spite of sharply varied results (some neurons showing large potentiation, lasting for >1 h, and many little or none), overall there was a significant and similar potentiation of IPSP conductance, both for the early (at approximate to 30 ms) and later (at approximate to 140 ms) components of IPSPs or IPSCs: by 35.1 +/- 10.25% (mean +/- SE;for n = 24, P = 0.0023) and 36.5 +/- 16.3% (for n = 19, P = 0.038), respectively. The similar potentiation of the early and late IPSP points to a presynaptic mechanism of LTP. Overall, the LTP was statistically significant only when 2-DG was applied in the absence of glutamate antagonists. Tetanic stimulations (in presence or absence of glutamate antagonists) only depressed IPSPs (by half). In conclusion, although smaller and more variable, 2-DG-induced LTP of inhibitory synapses appears to be broadly similar to the 2-DG-induced LTP of excitatory postsynaptic potentials previously observed in CA1.

关键词： 2-氨基-5-膦酰基戊酸盐/药理学抗代谢药/药理学脱氧葡萄糖/药理学兴奋性氨基酸拮抗剂/药理学海马/细胞学海马/生理学长时程增强/药物作用长时程增强/生理学微电极神经抑制/药物作用神经抑制/生理学膜片钳术锥体细胞/化学锥体细胞/药物作用锥体细胞/生理学喹恶啉类/药理学大鼠 Sprague-Dawley 受体 N-甲基-D-天冬氨酸/生理学动物男(雄)性小鼠大鼠

来源：评论

学校读者我要写书评

暂无评论

Differentiation between senescence (M1) and crisis (M2) in human fibroblast cultures

引用

EXPERIMENTAL CELL RESEARCH 1999年第2期253卷 519-522页

作者： Wei, WY Sedivy, JM Brown Univ Dept Mol Biol Cell Biol & Biochem Div Biol & Med Providence RI 02912 USA

Normal human fibroblasts undergo only a limited number of divisions in culture and eventually enter a nonreplicative state designated senescence or mortality stage 1 (M1). Expression of certain viral oncogenes, such as the SV40 large T antigen (SV40 T-Ag), can elicit a significant extension of replicative life span, but these cultures eventually also cease dividing. This proliferative decline has been designated crisis or mortality stage 2 (M2). BrdU incorporation assays are commonly used to distinguish between senescence (<5% labeling index) and crisis (>30% labeling index). It has not been possible, however, to ascertain whether the high labeling index, indicative of ongoing DNA replication, was caused by the presence of T-Ag. We used gene targeting to knock out both copies of the p21(CIP1/WAF1) gene in presenescent human fibroblasts. p21 -/- cells displayed an extended life span but eventually entered a nonproliferative state. In their terminally nonproliferative state both p21 +/+ and p21 -/-cultures were positive for the senescence-associated beta-galactosidase (SA-beta-gal) activity;in contrast, the labeling index of p21 +/+ cells was low (<5%) whereas the labeling index of p21 -/- cells was high (>30%). The observation that p21 -/- and SV40 T-Ag-expressing cells behave identically with respect to life span extension as well as the high labeling index in the terminally nonproliferative state indicates that crisis is not a phenomenon induced solely by viral oncogenes, but a physiological state resulting from the bypass of normal senescence mechanisms. The widely used biomarker for senescence, SA-beta-gal, cannot distinguish between senescence and crisis. We propose that all SA-beta-gal-positive cultures should be further examined for their BrdU labeling index, (C) 1999 Academic Press.

关键词：抗代谢药/药理学溴脱氧尿苷/药理学细胞衰老/生理学细胞培养的周期素依赖激酶抑制剂p21 细胞周期蛋白类/遗传学细胞学技术/标准成纤维细胞/细胞学基因表达调控酶学/药物作用基因表达调控酶学/生理学分子生物学/方法分子生物学/标准可重复性结果 β半乳糖苷酶类/遗传学人类

来源：评论

学校读者我要写书评

暂无评论

建议与咨询留下您的常用邮箱和电话号码，以便我们向您反馈解决方案和替代方法

时间限定

文献类型

馆藏选择

核心期刊

语言

文献类型

帮助

文字说明：

检索规则说明：

检索范例：

分类表

所选分类

限定检索结果

文献类型

馆藏范围

日期分布

学科分类号

主题

机构

作者

语言

请选择保存的检索档案：

请选择收藏分类：

通借通还

建议与咨询 留下您的常用邮箱和电话号码，以便我们向您反馈解决方案和替代方法

时间限定

文献类型

馆藏选择

核心期刊

语言

文献类型

帮助

文字说明：

检索规则说明：

检索范例：

分类表

所选分类

限定检索结果

文献类型

馆藏范围

日期分布

学科分类号

主题

机构

作者

语言

请选择保存的检索档案： 新增检索档案 确定 取消

请选择收藏分类： 新增自定义分类 确定 取消

通借通还

建议与咨询留下您的常用邮箱和电话号码，以便我们向您反馈解决方案和替代方法

请选择保存的检索档案：

请选择收藏分类：