Regulation of calcium influx by second messengers in rat mast cells

Biphasic increases in the free intracellular calcium concentration, consisting of a large initial transient followed by a sustained elevation, are frequently observed in non-excitable cells following stimulation. In rat peritoneal mast cells a cAMP- and Ca-activated chloride current can interact with IP3-dependent calcium influx to provide the sustained elevation of intracellular Ca concentration following transient IP3-induced release of calcium from intracellular stores. This novel combination of second messenger systems provides a flexible means to modulate calcium-dependent processes such as exocytosis.     

Direct modulation of Aplysia S-K+ channels by a 12-lipoxygenase metabolite of arachidonic acid

Lipoxygenase metabolites of arachidonic acid have recently been shown to modulate the activity of ion channels in nerve and muscle cells. The mechanism of action of these metabolites is, however, unknown. In sensory neurons of Aplysia, the S-K- channel is under the dual modulatory control of 5-hydroxytryptamine (5-HT), which decreases the number of active S channels through cyclic AMP-dependent phosphorylation, and the neuropeptide FMRFamide, which increases the probability of S-channel opening through the 12-lipoxygenase metabolite 12-hydroperoxyeicosatetraenoic acid (12-HPETE). Here we report that the increase in the probability of S-channel opening with FMRFamide is mimicked by application of 12-HPETE to cell-free membrane patches that lack ATP and GTP. Thus, 12-HPETE can act directly to modulate S-channel activity, independently of protein phosphorylation or dephosphorylation, G-protein activation or cyclic nucleotides.     

Arachidonic acid metabolites as mediators of somatostatin-induced increase of neuronal M-current

The M-current (IM) is a time- and voltage-dependent K+ current that persists at slightly depolarized membrane potentials. IM is reduced by muscarinic cholinergic agonists and certain peptides, and is thought to be responsible in part for the slow and late slow excitatory postsynaptic potentials in sympathetic neurons. Recently, we reported that IM in hippocampal neurons was also augmented by somatostatin-14 and -28 suggesting that two different receptors reciprocally regulate one neuronal channel type. Muscarinic effects on IM may be mediated by various components of the phosphatidylinositol phosphate pathway. We now report the involvement of a different second messenger pathway, that generated by phospholipase A2, in the somatostatin-induced augmentation of IM in hippocampal cells. This pathway generates arachidonic acid from which leukotrienes can be produced by lipoxygenases. We find that the IM-augmenting effects of somatostatin are abolished by two substances that can inhibit phospholipase A2, quinacrine and 4-bromophenacyl bromide, and that both arachidonic acid and leukotriene C4 mimic the effects of somatostatin-14 on hippocampal pyramidal neurons in vitro. Arachidonic and somatostatin effects are blocked by a lipoxygenase inhibitor, implicating an arachidonic acid metabolite, perhaps a leukotriene, in the somatostatin effect.     

The LDL receptor pathway delivers arachidonic acid for eicosanoid formation in cells stimulated by platelet-derived growth factor

Animal cells can convert 20-carbon polyunsaturated fatty acids into prostaglandins (PGs) and leukotrienes. These locally produced mediators of inflammatory and immunological reactions act in an autocrine or paracrine fashion. Arachidonic acid (AA), the precursor of most PGs and leukotrienes, is present in the form of lipid esters within plasma lipoproteins and cannot be synthesised de novo by animal cells. Therefore, AA or its plant-derived precursor, linoleic acid, must be provided to cells if PGs or leukotrienes are to be formed. Because several classes of lipoproteins, including low-density lipoproteins (LDL), very-low-density lipoproteins, and chylomicron remnants, are taken up by means of the LDL receptor, and because LDL and very-low-density lipoproteins, but not high-density lipoproteins, stimulate PG synthesis, we have suggested previously that PG formation is directly linked to the LDL pathway. Using fibroblasts with the receptor-negative phenotype of familial hypercholesterolaemia and anti-LDL receptor antibodies, we show here that LDL deliver AA for PG production and that an LDL receptor-dependent feedback mechanism inhibits the activity of PGH synthase, the rate-limiting enzyme of PG synthesis. These results indicate that the LDL pathway has a regulatory role in PG synthesis, in addition to its well-known role in the maintenance of cellular cholesterol homeostasis.     

Dopamine activation of the arachidonic acid cascade as a basis for D1/D2 receptor synergism

Understanding the actions of the neurotransmitter dopamine in the brain is important in view of its roles in neuropsychiatric illnesses. Dopamine D1 receptors, which stimulate both adenylyl cyclase and phospholipase C, and D2 receptors, which inhibit them, can nevertheless act synergistically to produce many electrophysiological and behavioral responses. Because this functional synergism can occur at the level of single neurons, another, as yet unidentified, signalling pathway activated by dopamine has been hypothesized. We report here that in Chinese hamster ovary (CHO) cells transfected with the D2 receptor complementary DNA, D2 agonists potently enhanced arachidonic acid release, provided that such release has been initiated by stimulating constitutive purinergic receptors or by increasing intracellular Ca2+. In CHO cells expressed D1 receptors, D1 agonists exert no such effect. When D1 and D2 receptors are coexpressed, however, activation of both subtypes results in a marked synergistic potentiation of arachidonic acid release. The numerous actions of arachidonic acid and its metabolites in neuronal signal transduction suggest that facilitation of its release may be implicated in dopaminergic responses, such as feedback inhibition mediated by D2 autoreceptors, and may constitute a molecular basis for D1/D2 receptor synergism.     

2-己基咪唑作为铜的盐酸酸洗缓蚀剂作用机理的研究

通过失重法研究了2-己基咪唑(2-HeIM)在5%盐酸中对铜的酸洗缓蚀性能.探讨了温度和2-HeIM浓度对缓蚀效果的影响,从中得出了2-HeIM在铜表面的吸附等温式,计算了吸附热及2-HeIM的加入对铜在盐酸中腐蚀反应活化能的影响,进而探讨了2-HeIM对铜的缓蚀作用机理.结果表明,30℃下,在5%盐酸中,当2-HeIM的浓度在6 mmol/L以下缓蚀率随2-HeIM浓度的增加而增加,当浓度达到6 mmol/L时,缓蚀率趋于定值.在2 mmol/L到6 mmol/L浓度范围内吸附在铜表面的2-HeIM分子间的作用力整体表现为引力;2-HeIM在铜表面的吸附是吸热反应;2-HeIM的加入降低了铜的腐蚀反应活化能.     

环保型阻垢剂聚天冬氨酸的研制

以天门冬氨酸为单体 ,采用加热缩聚法 ,合成了聚天冬氨酸 ,研究了温度、时间对收率的关系。测定了不同浓度下的聚天冬氨酸的阻垢性能 ,实验结果表明 ,聚天冬氨酸具有较好的阻垢分散性能 ,是一种优良的环保型水质稳定剂。     

Arachidonic acid metabolites as intracellular modulators of the G protein-gated cardiac K+ channel

Arachidonic acid is released from cell membranes in response to receptor-dependent as well as receptor-independent stimulation in various cells, including cardiac myocytes. Arachidonic acid is converted to prostaglandins by cyclooxygenase and to leukotrienes by 5-lipoxygenase, metabolites which are very biologically active and modulate cellular functions such as platelet aggregation, smooth muscle contraction and neural excitation. The molecular mechanisms underlying their modulations are, however, still badly understood. Here, we report that the 5-lipoxygenase metabolites of arachidonic acid activate the pertussis toxin-sensitive G protein-gated muscarinic K+ channel (IK.ACh): arachidonic acid activation of IK.ACh was prevented by the lipoxygenase inhibitors, nordihydroguaiaretic acid and AA-861; leukotriene A4 and C4 activated IK.ACh. The activation occurred in pertussis toxin-treated atrial cells and ceased when inside-out patches were formed but the patches were still susceptible to stimulation by GTP and to inhibition by GDP-beta-S. These results indicate that arachidonic acid metabolites may stimulate the G-protein in a receptor-independent way.     

Arachidonic acid induces a prolonged inhibition of glutamate uptake into glial cells

Activation of NMDA (N-methyl-D-aspartate) receptors by neurotransmitter glutamate stimulates phospholipase A2 to release arachidonic acid. This second messenger facilitates long-term potentiation of glutamatergic synapses in the hippocampus, possibly by blocking glutamate uptake. We have studied the effect of arachidonic acid on glutamate uptake into glial cells using the whole-cell patch-clamp technique to monitor the uptake electrically. Micromolar levels of arachidonic acid inhibit glutamate uptake, mainly by reducing the maximum uptake rate with only small effects on the affinity for external glutamate and sodium. On removal of arachidonic acid a rapid (5 minutes) phase of partial recovery is followed by a maintained suppression of uptake lasting at least 20 minutes. Surprisingly, the action of arachidonic acid is unaffected by cyclo-oxygenase or lipoxygenase inhibitors suggesting that it inhibits uptake directly, possibly by increasing membrane fluidity. As blockade of phospholipase A2 prevents the induction of long-term potentiation (LTP), inhibition of glutamate uptake by arachidonic acid may contribute to the increase of synaptic gain that occurs in LTP. During anoxia, release of arachidonic acid could severely compromise glutamate uptake and thus contribute to neuronal death.     

盐酸溶液中乌鲁托品对钢的缓蚀性能

用电化学阻抗谱(EIS)和开路电位测量法(OCPM)研究了在1 mol·L-1盐酸溶液中乌鲁托品(UP)与45#钢的界面吸附及缓蚀行为.EIS表明:随着缓蚀剂UP浓度的增大,吸附膜逐渐形成,电荷传递电阻增大.在缓蚀剂浓度为0.01 mol·L-1时,缓蚀效率出现最大值;大于该浓度时,缓蚀效率下降.OCPM表明:加缓蚀剂UP前后体系自腐蚀电位的改变与温度的倒数呈线性关系.UP对阳极过程有抑制作用,是阳极型缓蚀剂;吸附热为-35 kJ/mol,吸附形式为物理吸附.     

HCl介质中双子季铵盐表面活性剂对碳钢的缓蚀性能

采用质量损失法和电化学方法,研究羟基丙撑双(十二烷基二甲基氯化铵)(HPB)双子型季铵盐表面活性剂在40℃1.0 mol/L HCl、KCl、NaCl和HCl复配缓蚀介质中对碳钢的缓蚀性能。结果表明:HPB是一种性能优异的缓蚀剂,随着浓度的增大,其缓蚀效率逐渐增大,在质量浓度为50 mg/L时,缓蚀效率能达到98%。通过对吸附等温式的探讨,计算出其吸附自由能为-14.64 kJ/mol,推断出HPB在碳钢表面的吸附行为主要为物理吸附。电化学方法的测试结果表明,HPB是一种以抑制阴极反应为主的混合型缓蚀剂。     

不同表面活性剂在盐酸介质中对钢的缓蚀协同效应

用失重法研究了在盐酸介质中，十二烷基苯磺酸钠(DBSAS)和非离子表面活性剂聚乙二醇辛基苯基醚(OP)对钢的缓蚀协同效应，讨论了产生协同效应的原因。     

A nucleotide regulatory site for somatostatin inhibition of adenylate cyclase in S49 lymphoma cells

The cyc- variants of S49 lymphoma cells have served as powerful tools for studying the components and mechanisms of hormone-induced adenylate cyclase stimulation, as these cells are deficient in the guanine nucleotide regulatory site (Ns) mediating hormone, guanine nucleotide, cholera toxin and fluoride-induced stimulations of the enzyme. Because of this deficiency, membranes of these cells have been used for reconstitution of the system by inserting the coupling component derived from other cell types. The hormone-sensitive adenylate cyclase is not only stimulated by hormones but can also be inhibited by a wide variety of hormones and neurotransmitters, and there is some evidence that hormonal inhibition may be mediated by a distinct guanine nucleotide regulatory site. Studies in cyc- cells lacking a functional Ns may therefore answer this unresolved, important question. We have recently observed that stable GTP analogues can inhibit cyc- adenylate cyclase stimulated by purified, preactivated Ns or forskolin, which can activate adenylate cyclase even in the absence of a functional Ns (ref. 10). The data indicated that these Ns-deficient cells contain an inhibitory guanine nucleotide site, Ni. To strengthen this concept, we investigated whether the cyc- adenylate cyclase can be inhibited by a hormone. We report here that somatostatin decreases cyclic AMP levels in cyc- cells, inhibits the forskolin-stimulated adenylate cyclase and causes a concomitant increase in a high affinity GTPase activity in cyc- membranes. The data strongly suggest that both the hormone- and guanine nucleotide-induced adenylate cyclase inhibitions in cyc- cells are mediated by Ni and that the mechanisms of activation and inactivation of Ni are similar to those established for Ns.     

聚天门冬氨酸阻垢作用的研究

以L 天门冬氨酸为原料采用聚合—水解二步反应合成出具有优异阻垢性能的聚天冬氨酸 ,考察分析了它对碳酸钙的阻垢作用及相关机理     

Gemini表面活性剂与卤离子对钢在磷酸介质中缓蚀协同效应

通过失重法与极化曲线法考察了季铵盐型Gemini表面活性剂1,3-双(十二烷基二甲基溴化铵)丙烷(简写为12-3-12)及其与卤离子复合体系对冷轧钢在1 mol.L-1磷酸溶液中的缓蚀协同效应.实验结果表明,在一定浓度氯离子或溴离子的存在下,浓度很低的Gemini表面活性剂12-3-12(1×10-4mol.L-1)就可以对冷轧钢在磷酸介质中起到很好的缓蚀效果;通过在Gemini表面活性剂12-3-12溶液中加入一定浓度的Cl-或Br-构筑复合的缓蚀体系,利用表面活性剂与卤离子之间显著的缓蚀协同效应,大大降低了Gemini表面活性剂在缓蚀体系中的用量,极大地降低了Gemini表面活性剂作为酸介质中钢的缓蚀剂的综合使用成本;对酸介质中Gemini表面活性剂复合缓蚀体系在金属表面的吸附机理进行了探讨,并通过Langmuir吸附理论和相关公式得到了相关热力学参数.     

皂土附载复合固体酸催化剂合成DOP的研究

本文报道用皂土附载复合固体酸为催化剂合成 DOP.实验结果表明,该催化剂具有催化活性强,选择性高,化学和热稳定性好,制备简便,价格低廉,无腐蚀性等优点;而且可以重复使用4～5次。     

Superoxide dismutase as a target for the selective killing of cancer cells

Superoxide dismutases (SOD) are essential enzymes that eliminate superoxide radical (O2-) and thus protect cells from damage induced by free radicals. The active O2- production and low SOD activity in cancer cells may render the malignant cells highly dependent on SOD for survival and sensitive to inhibition of SOD. Here we report that certain oestrogen derivatives selectively kill human leukaemia cells but not normal lymphocytes. Using complementary DNA microarray and biochemical approaches, we identify SOD as a target of this drug action and show that chemical modifications at the 2-carbon (2-OH, 2-OCH3) of the derivatives are essential for SOD inhibition and for apoptosis induction. Inhibition of SOD causes accumulation of cellular O2- and leads to free-radical-mediated damage to mitochondrial membranes, the release of cytochrome c from mitochondria and apoptosis of the cancer cells. Our results indicate that targeting SOD may be a promising approach to the selective killing of cancer cells, and that mechanism-based combinations of SOD inhibitors with free-radical-producing agents may have clinical applications.     

分子筛型固体酸催化剂用于长直链烯烃和苯的烷基化反应

以分子筛型固体酸代替氢氟酸作催化剂,研究了长直链烯烃和苯的烷基化反应。对各种类型分子筛的研究表明:以金属阳离子交换的Y型分子筛为催化剂,在常压、苯/烯=8(摩尔比)、烯/剂=6(重量比)的条件下,反应0.5小时,烯烃的转化率可达97%以上,苯的单烷基化的选择性在90%以上。提高反应温度和压力可进一步提高烯烃的转化率,当反应温度150℃、压力2MPa、重量空速6h~(-1)时,烯烃转化率高于90%的时间可达100小时以上。