硝酸酯类药物及钙离子拮抗剂对胃食管反流的影响

目的:探讨硝酸酯类药物及钙离子拮抗剂对胃食管反流症状的影响.方法:选取2010年1月-2011年1月我院收治的心血管病患者99例,根据服用药物不同分为三组:单独使用硝酸酯类药物组35例;单独使用钙离子拮抗剂组31例;以及对照组(既无硝酸酯类药物也无钙离子拮抗剂)33例.比较三组患者胃食管反流症状积分.结果:单纯使用硝酸酯类药物组比其他药物组及钙离子拮抗剂组的病人在早饱、恶心和呕吐的症状积分上较高并存在明显差异(P＜0.05).钙离子拮抗剂组与硝酸酯类药物组比较烧心症状积分较高并有统计学上明显差异(P＜0.05).钙离子拮抗剂组与其他药物组比较烧心及返酸积分较高,但差异无统计学意义(P＞0.05).结论:硝酸酯类药物在早饱、恶心、呕吐几方面比使用其他类药物更多地引起症状.钙离子拮抗剂似乎更易引起反酸、烧心等胃食管反流症状,但未得到证实.     

EGTA和La3+对几种逆境诱导辣椒样半萜 环化酶基因表达的影响

用钙离子螯合剂EGTA及细胞膜钙离子通道拮抗剂La     

钙与钙调素对柑橘原生质体抗冻性的影响

钙与钙调素对柑橘原生质体低温锻炼过程中抗冻力的获得有影响。加钙残余螯合剂或钙调素（ChM）拮抗剂TFP,能明显抑制柑橘原生质体抗冻性的表达。钙离子载体A23187可提高未经低温锻炼的原生质体抗冻力,但该作用在钙调素拮抗剂TFP参入下则减弱,表明原生质体抗冻力的表达受钙和钙调素的调节。     

冠脉痉挛致急性冠脉综合征患者的临床探讨

目的:分析冠脉痉挛致急性冠脉综合征患者的临床特点。方法:回顾分析在2013年12月至2014年12月期间,从我院收治的急性冠脉综合征患者中抽取35例冠脉痉挛致急性冠脉综合征的患者作为研究对象,分析其临床特点。结果:吸烟患者的发病几率高,硝酸酯以及钙离子拮抗剂具有较好的治疗效果。结论:冠脉痉挛致急性冠脉综合征主要是在清晨以及夜间发作,持续的时间长;服用硝酸酯以及钙离子拮抗剂的治疗同时改变患者不良的生活习惯,才可以获得明显的治疗效果。     

钙-钙调素与小麦苗中热激蛋白的诱导

在 34℃热激条件下 ,种子经钙预处理的小麦苗中的钙调素含量随着热激时间的延长而增加 ,热激 90min时达最大值 ,而种子用钙离子螯合剂EGTA预处理的小麦苗中钙调素含量无明显增加。种子用EGTA及钙调素拮抗剂CPZ和TFP预处理的小麦幼苗在 34℃热激时 ,热激蛋白的合成量减少。 4d的小麦幼苗在34℃或 37℃热激条件下 ,能诱导耐热性的获得 ,分别用EGTA、钙离子通道阻断剂易博定、钙调素拮抗剂TFP或CPZ预处理种子后 ,所得幼苗热诱导的耐热性的提高程度有所下降     

钙与钙调素对柑橘原生质体抗冻性的影响

钙与钙调素对柑橘原生质体低温锻炼过程中抗冻力的获得有影响。加钙螯合剂或钙调素拮抗剂ＴＦＰ,能明显抑制柑橘原生质体抗冻性的表达。钙离子载体Ａ２３１８７可提高未经低温锻炼的原生质体抗冻力,但该作用在钙调素拮抗剂ＴＦＰ参入下则减弱,表明原生质体抗冻力的表达受钙和钙调素的调节。     

钙—钙调素与小麦苗中热激蛋白的诱导

在３４℃热激条件下,种子经钙预处理的小麦苗中的钙调素含量随着热激时间的延长而增加,热激９０ｍｉｎ时达最大值,面种子用钙离子螯合剂ＥＧＴＡ预处理的小麦苗中钙调素含量无明显增加。种子用ＥＧＴＡ及钙调素拮抗剂ＣＰＺ和ＴＦＰ预处理的小麦幼苗在３４℃热激时,热激蛋白的合成量减少。４ｄ的小麦幼苗在３４℃或３７℃热激条件下,能诱导耐热性的获得,分别用ＥＧＴＡ、钙离子通道阻断剂易博定、钙调素拮抗剂ＴＦＰ或ＣＰＺ预     

烟草培养细胞中钙离子,钙调素与细胞质流的关系

烟草愈伤组织的培养细胞中,当钙离子载体将Ca~(2 )导入细胞时,细胞质流停止.CaM拮抗剂试验表明,高钙使细胞质流停止的效应可能与CaM无关,除W7外的多种CaM拮抗剂都明显而且可逆地抑制细胞质流。酶联免疫吸附分析(ELISA)检出培养细胞中存在有CaM。间接酶标免疫组织化学分析进一步证明CaM存在于胞质条纹中。     

精氨酸加压素C端片段（4—8）对C6神经胶质瘤细胞胞内 …

ＺＮＣ（Ｃ）ＰＲ是精氨酸加压素（ＡＶＰ）在脑内的天然酶解产物,具有促进学习记忆的中枢效应。为了进一步阐明其作用的分子机制,以Ｃ６神经胶质瘤细胞为模型,用荧光染料Ｆｌｕｏ３负载细胞,用激光共聚焦显微镜观察胞内自由钙离子的变化情况。民现ＺＮＣ（Ｃ）ＰＲ能促进胞内钙离子的升高,这种作用是剂量依赖的,并能被其拮抗剂ＺＤＣ（Ｃ）ＰＲ所抑制,胞外钙离子对该升高没有影响。     

视黄酸对海马神经元细胞内钙离子浓度的影响

探讨全反式视黄酸(all-trans retinoic acid,atRA)对原代培养的海马神经元胞内钙离子浓度的影响,以进一步了解atRA参与学习记忆可能机制。分离新生Wistar大鼠海马,采用添加B27的无血清培养液进行海马神经元原代培养,免疫荧光鉴定培养的神经细胞;以fura-2/AM温育海马神经元,采用钙离子测定系统动态观察视黄酸对海马细胞内钙离子浓度的影响。结果显示:(1)培养的神经元纯度达90%;(2)atRA作用于海马神经元,能引起海马神经元胞内钙离子浓度的升高;(3)这种升高与atRA浓度及神经元的发育时间相关;(4)钙离子升高的具体方式是通过细胞外钙离子内流;(5)视黄酸核受体alpha(RARα)的拮抗剂Ro41-5253(Ro)对atRA升高的神经元胞内钙离子浓度有抑制作用。atRA与RARα结合,促使海马神经元胞外钙离子的内流,这可能是atRA参与学习记忆的机制之一。     

Effects of calcium channel antagonists on the corpora allata of adult male loreyi leafworm Mythimna loreyi: juvenile hormone acids release and intracellular calcium level

The effects of voltage-dependent calcium channel (VDCC) antagonists and the non-specific calcium channel antagonists on both juvenile hormone acids (JHA) release and cytosolic free calcium concentration ([Ca2+]i) are investigated in the corpora allata (CA) of the adult males loreyi leafworm Mythimna loreyi. The VDCC antagonists used in this study are: the L-type antagonists diltiazem, nifedipine, and verapamil, the N-type antagonist omega-Conotoxin (CgTx) GVIA, the N- and P/Q-type antagonist omega-CgTx MVIIC, and the T-type antagonist amiloride. The non-specific calcium channel antagonists used in this study were cadmium (Cd2+), cobalt (Co2+), nickle (Ni2+), and lanthanum (La3+). The results show that both the DHPs-sensitive L-type antagonist nifedipine and the N-type antagonist omega-CgTx GVIA were able to inhibit JHA release, but only omega-CgTx GVIA was able to reduce the [Ca2+]i. Among the non-specific calcium channel antagonists, Cd2+ is the most potent in reducing JHA release but without obvious effect on the [Ca2+]i, La3+ significantly increases the [Ca2+]i but without effect on JHA release.     

氨基甙类抗生素对家兔离体颈动脉窦压力感受器放电的抑制作用

实验用自制的压力感受器标本灌流－记录一体化装置,研究氨基甙类抗生素,胞外钙离子浓度变化和L－型钙通道拮抗剂对家兔离体颈动脉窦压力感受器活动（CS－BRA）的影响,研究中发现,（1）链霉素（0．24－0．75mmol/L)和庆大霉素（0．43－1．29mmol/L)浓度依赖性地抑制S－BRA,停药后可基本恢复;（2）高钙灌流液（3．3mmol/L)抑制S－BRA,而微量钙灌流液（10^-5mmol/L数量级）兴奋CS－BRA;（3）维拉帕米和地尔硫卓和选择怀阻断L－型钙通道的有效浓度范围内（＜106-7mol/L)对CS－BRA没有显著影响,在更高浓度（＞10^-6mol/L)时,则抑制CSBRA。结果表明。（1）氨基甙类抗生素特异性地抑制CS－BRA,是一种新的研究压力感受器活动的工具药;（2）钙离子不是形成压力感受器发生器电位的主要离子,而且L－型钙通道在CS－BRA中没有显著作用;（3）氨基甙类抗生素对CS－BRA的抑制作用可能不是阻断L－型钙通道实现的。     

Pyridyl amides as potent inhibitors of T-type calcium channels

A novel series of amide T-type calcium channel antagonists were prepared and evaluated using in vitro and in vivo assays. Optimization of the screening hit 3 led to identification of the potent and selective T-type antagonist 37 that displayed in vivo efficacy in rodent models of epilepsy and sleep.     

Effect of Ca2+ channel antagonists on the acrosome reaction of guinea pig and golden hamster spermatozoa

The effects of Ca²⁺ channel antagonists on the motility and acrosome reaction of guinea pig spermatozoa were examined by incubating the spermatozoa continuously in Ca²⁺-containing capacitating media with 10^?6 M to 10^?4 M antagonist. Antagonists tested were four voltage-gated Ca²⁺ channel antagonists (verapamil, nifedipine, nimodipine, and FR–34235) and two ligand-gated channel antagonists (NaNO₂ and Na-nitroprusside). None of these antagonists could block the acrosome reaction. Instead, three antagonists (verapamil, nimodipine, and FR-34235, each at 10^?4 M) accelerated the onset of the acrosome reaction with a subsequent decrease in sperm motility. Nifedipine and Na-nitroprusside at the same concentration caused a complete loss of sperm motility by 4 hr of incubation with no substantial effect on the rate of acrosome reaction. The detrimental effect of antagonists on the motility of spermatozoa appears to be due to a direct, Ca²⁺-independent, membrane-perturbing action of the reagents. The acrosome reaction was not inhibited when guinea pig spermatozoa were precapacitated in Ca²⁺-free medium (with a low concentration of lysolecithin) in the continuous presence of antagonists. An acceleration of the onset of the acrosome reaction by verapamil (10^?4 M) was also demonstrated in the golden hamster. These results may be interpreted as indicating that the entry of extracellular Ca²⁺ into spermatozoa, which triggers the acrosome reaction of guinea pig and hamster spermatozoa, is not mediated by Ca²⁺ channels. This is in marked contrast with the case reported in invertebrate spermatozoa. Possible mechanisms by which some of the antagonists stimulate the acrosome reaction and affect the motility of mammalian spermatozoa are discussed.     

1,4-Dihydropyridines as calcium channel ligands and privileged structures

1. The 1,4-dihydropyridine nucleus serves as the scaffold for important cardiovascular drugs—calcium antagonists—including nifedipine, nitrendipine, amlodipine, and nisoldipine, which exert their antihypertensive and antianginal actions through actions at voltage-gated calcium channels of the Ca_V1 (L-type) class.2. These drugs act at a specific receptor site for which defined structure-activity relationships exist, including stereoselectivity.3. Despite the widespread occurrence of the Ca_V1 class of channel, the calcium antagonists exhibit significant selectivity of action in the cardiovascular system. This selectivity arises from a number of factors including subtype of channel, state-dependent interactions, pharmacokinetics, and mode of calcium mobilization.4. The 1,4-dihydropyridine nucleus is also a privileged structure or scaffold that can, when appropriately decorated substituents, interact at diverse receptors and ion channels, including potassium and sodium channels and receptors of the G-protein class.     

Binding of [3H]phencyclidine to membranes from housefly thoracic muscles

The binding of [³H]phencyclidine ([³H]PCP) to a preparation of housefly thoracic muscle membranes was studied. Specific [³H]PCP binding saturated with both time and at concentrations of the radiolabeled ligand greater than 20 nM. One binding site with a K_D of 10.7 nM and a B_max of 3.9 pmol/mg protein was observed. Specific [³H]PCP binding was also readily reversible with a half-time of dissociation (t_1/2) of 13.8 min and varied proportionately with tissue concentration. Of the drugs tested, specific [³H]PCP binding was inhibited by PCP analogs, antipsychotics, antidepressants, Ca²⁺ channel antagonists, and K⁺ channel blockers. [³H]PCP binding was unaffected by addition of carbamylcholine or L-glutamate in absence or presence of ATP, GTP, cAMP, or cGMP. Though the identity of the [³H]PCP binding protein in housefly muscle membranes is still unclear, it is more likely to be an ionic channel such as K⁺ or Ca²⁺ channels than a neurotransmitter receptor.     

Arabidopsis thaliana root non-selective cation channels mediate calcium uptake and are involved in growth

Calcium is a critical structural and regulatory nutrient in plants. However, mechanisms of its uptake by root cells are poorly understood. We have found that Ca2+ influx in Arabidopsis root epidermal protoplasts is mediated by voltage-independent rapidly activating Ca2+-permeable non-selective cation channels (NSCCs). NSCCs showed the following permeability (P) sequence: PCa (1.00) = PBa (0.93) > PZn (0.51), PCa/PNa = 0.19, PCa/PK = 0.14. They were inhibited by quinine, Gd3+, La3+ and the His modifier diethylpyrocarbonate, but not by the Ca2+ or K+ channel antagonists, verapamil and tetraethylammonium (TEA+). Single channel conductance measured in 20 mm external Ca2+ was 5.9 pS. Calcium-permeable NSCCs co-existed with hyperpolarisation-activated Ca2+ channels (HACCs), which activated 40-60 min after forming the whole-cell configuration. HACCs activated at voltages <-130 to -150 mV, showed slow activation kinetics and were regulated by cytosolic Ca2+ ([Ca2+]cyt). Using aequorin-expressing plants, a linear relationship between membrane potential (Vm) and resting [Ca2+]cyt was observed, indicating the involvement of NSCCs. Intact root 45Ca2+ influx was reduced by Gd3+ (NSCC blocker) but was verapamil and TEA+ insensitive. In the root elongation zone, both root net Ca2+ influx (measured by Ca2+-selective vibrating microelectrode) and NSCC activity were increased compared to the mature epidermis, suggesting the involvement of NSCC in growth. A Ca2+ acquisition system based on NSCC and HACC co-existence is proposed. In mature epidermal cells, NSCC-mediated Ca2+ influx dominates whereas in specialised root cells (root hairs and elongation zone cells) where elevated [Ca2+]cyt activates HACCs, HACC-mediated Ca2+ influx predominates.     

Hydroxyproline-induced Helical Disruption in Conantokin Rl-B Affects Subunit-selective Antagonistic Activities toward Ion Channels of N-Methyl-d-aspartate Receptors

Conantokins are ∼20-amino acid peptides present in predatory marine snail venoms that function as allosteric antagonists of ion channels of the N-methyl-d-aspartate receptor (NMDAR). These peptides possess a high percentage of post-/co-translationally modified amino acids, particularly γ-carboxyglutamate (Gla). Appropriately spaced Gla residues allow binding of functional divalent cations, which induces end-to-end α-helices in many conantokins. A smaller number of these peptides additionally contain 4-hydroxyproline (Hyp). Hyp should prevent adoption of the metal ion-induced full α-helix, with unknown functional consequences. To address this disparity, as well as the role of Hyp in conantokins, we have solved the high resolution three-dimensional solution structure of a Gla/Hyp-containing 18-residue conantokin, conRl-B, by high field NMR spectroscopy. We show that Hyp¹⁰ disrupts only a small region of the α-helix of the Mn²⁺·peptide complex, which displays cation-induced α-helices on each terminus of the peptide. The function of conRl-B was examined by measuring its inhibition of NMDA/Gly-mediated current through NMDAR ion channels in mouse cortical neurons. The conRl-B displays high inhibitory selectivity for subclasses of NMDARs that contain the functionally important GluN2B subunit. Replacement of Hyp¹⁰ with N⁸Q results in a Mg²⁺-complexed end-to-end α-helix, accompanied by attenuation of NMDAR inhibitory activity. However, replacement of Hyp¹⁰ with Pro¹⁰ allowed the resulting peptide to retain its inhibitory property but diminished its GluN2B specificity. Thus, these modified amino acids, in specific peptide backbones, play critical roles in their subunit-selective inhibition of NMDAR ion channels, a finding that can be employed to design NMDAR antagonists that function at ion channels of distinct NMDAR subclasses.     

Voltage-sensitive calcium flux promoted by vesicles in an isolated cardiac sarcolemma preparation

Summary The effect of membrane potential on the vesicular uptake of calcium in an isolated cardiac sarcolemma preparation from canine ventricle was evaluated. Membrane potentials were developed by the establishment of potassium gradients across the vesicular membranes. In the presence of valinomycin, the fluorescence changes of the voltage sensitive dye, diS-C₃-(5) were consistent with the development of potassium equilibrium potentials. Using EGTA to remove endogenous calcium from the preparation and to maintain a low intravesicular calcium concentration over time, the uptake of calcium was linear from 5 to 100 sec, in the absence of sodium, at both –98 and –1 mV. The rate of calcium uptake (calcium influx) was approximately twofold greater at –1 mV than at –98 mV, and prepolarization of the membrane potential to –98 mV did not enhance calcium influx upon subsequent depolarization to –1 mV. Hence, calcium influx was voltage-sensitive but not depolarization-induced and did not inactivate with time. Furthermore, the calcium influx was not inhibited by the organic calcium antagonists, which suggests that this flux did not occur via the transient calcium channel. Evaluation of calcium influx over a wide range of membrane potentials produced a profile consistent with the hypothesis that calcium entered the vesicles through the pathway responsible for the persistent inward current observed in voltage-clamped isolated myocytes. A model was proposed to account for these results.     

Leukotriene receptor antagonists,LY293111 and ONO-1078, protect neurons from the sPLA2-IB-induced neuronal cell death independently of blocking their receptors

In the ischemic brain, leukotrienes (LTs) are increased and their receptor antagonists protect neurons. However, it has not yet been sufficiently clarified how antagonists for LT receptors exhibit neuroprotective effects. In the present study, we evaluated protective effects of receptor antagonists for LTB₄ (LY293111) and cysteinyl LTs (ONO-1078) in the primary culture of rat cortical neurons. The group IB secretory phospholipase A₂ (sPLA₂-IB)-induced neuronal cell death had been established as the in vitro model for cerebral ischemia. sPLA₂-IB triggered the influx of Ca²⁺ into neurons via L-type voltage-dependent calcium channel (L-VDCC). Subsequently, the enzyme produced eicosanoids including LTB₄ before neuronal cell death. Neither administration of LTB₄ nor cysteinyl LTs such as LTC₄, LTD₄ and LTE₄ killed neurons. However, both LY293111 and ONO-1078 significantly prevented neurons from the neurotoxicity of sPLA₂-IB, suggesting that the two LT receptor blockers protected neurons through alternative pathways beside LT receptors. An L-VDCC blocker does not only inhibit the influx of Ca²⁺ into neurons but also rescues neurons from the sPLA₂-IB-induced neuronal cell death. The two LT receptor antagonists also blocked the sPLA₂-IB-induced Ca²⁺ influx significantly. Thus, LTs exhibited no neurotoxicity, but their receptor antagonists protected neurons directly in the in vitro ischemic model. Furthermore, the suppression of L-VDCC appeared to be involved in the neuroprotective effects of LY293111 and ONO-1078 independent of blocking their receptors.