Abstract:
:Calcium ions are versatile and universal biological signaling factors that regulate numerous cellular processes ranging from cell fertilization, to neuronal plasticity that underlies learning and memory, to cell death. For these functions to be properly executed, calcium signaling requires precise regulation, and failure of this regulation may tip the scales from a signal for life to a signal for death. Disruptions in calcium channel function can generate complex multi-system disorders collectively referred to as "calciumopathies" that can target essentially any cell type or organ. In this review, we focus on the multifaceted involvement of calcium signaling in the pathophysiology of Alzheimer's disease (AD), and summarize the various therapeutic options currently available to combat this disease. Detailing the series of disappointing AD clinical trial results on cognitive outcomes, we emphasize the urgency to design alternative therapeutic strategies if synaptic and memory functions are to be preserved. One such approach is to target early calcium channelopathies centrally linked to AD pathogenesis.
journal_name
Eur J Pharmacoljournal_title
European journal of pharmacologyauthors
Chakroborty S,Stutzmann GEdoi
10.1016/j.ejphar.2013.11.012subject
Has Abstractpub_date
2014-09-15 00:00:00pages
83-95eissn
0014-2999issn
1879-0712pii
S0014-2999(13)00883-2journal_volume
739pub_type
杂志文章,评审abstract::The aim of this study was to elucidate the possible mechanism of the potentiating action of metal ions (Cu2+, Hg2+, Ag+ and SeO3(2-)) on the ryanodine-induced contracture of the mouse diaphragm. The ryanodine contracture in the quiescent muscle could be augmented by either electrical stimulation or pretreatment with h...
journal_title:European journal of pharmacology
pub_type: 杂志文章
doi:10.1016/0014-2999(94)90443-x
更新日期:1994-01-04 00:00:00
abstract::We recently observed that the 5-hydroxytryptamine (5-HT)(1A) receptor antagonist N-[2-[4-(2-methoxyphenyl)-1-piperazinyl]ethyl]-N-(2-pyridinyl)-cycloh exanecarboxamide (WAY 100635) enhanced antipsychotic-induced catalepsy, which we hypothesized to be due to a blockade of tonic 5-HT(1A) receptor activation. Here, we ex...
journal_title:European journal of pharmacology
pub_type: 杂志文章
doi:10.1016/s0014-2999(00)00178-3
更新日期:2000-04-28 00:00:00
abstract::Galantamine is a reversible inhibitor of acetylcholinesterase and an allosteric-potentiating ligand of the nicotinic acetylcholine receptors. It is used for treating mild-to-moderate Alzheimer's disease. Interestingly, QT interval prolongation on the electrocardiogram (ECG), malignant ventricular arrhythmias and synco...
journal_title:European journal of pharmacology
pub_type: 杂志文章
doi:10.1016/j.ejphar.2012.02.002
更新日期:2012-04-15 00:00:00
abstract::The effects of several slow channel blockers were compared on the normal fast action potentials (APs) and the slow APs of guinea pig Purkinje fibers. In spontaneously-firing Purkinje fibers perfused with normal Tyrode solution, mesudipine (analog of nifedipine) at 10(-7) and 10(-6) M, had no significant effect on the ...
journal_title:European journal of pharmacology
pub_type: 杂志文章
doi:10.1016/0014-2999(83)90007-9
更新日期:1983-03-25 00:00:00
abstract::This review selectively explores some areas of pain research that, until recently, have been poorly understood. We have chosen four topics that relate to clinical pain and we discuss the underlying mechanisms and related pathophysiologies contributing to these pain states. A key issue in pain medicine involves crucial...
journal_title:European journal of pharmacology
pub_type: 杂志文章,评审
doi:10.1016/j.ejphar.2013.01.069
更新日期:2013-09-15 00:00:00
abstract::In rat stomach fundus, contractions induced by Ca2+ (1.8 mM) were strikingly potentiated by thapsigargin. This potentiation was partially inhibited by the blockers of Ca2+ release activated channels (CRACs), miconazole and SK&F96365 ([1-[beta-[3-(4-methoxyphenyl)propoxy]-4-methoxyphenethyl]-1H-imidazole, HCL]) and sli...
journal_title:European journal of pharmacology
pub_type: 杂志文章
doi:10.1016/s0014-2999(97)01537-9
更新日期:1998-01-19 00:00:00
abstract::Bacterial lipopolysaccharide and other immunostimulants induce gene expression of an isoform of nitric oxide synthase (iNOS) in vascular smooth muscle cells. This process is dependent on nuclear factor-kappa B (NF-kappa B) activation. The aim of this study was to investigate whether the NF-kappa B and Akt signaling pa...
journal_title:European journal of pharmacology
pub_type: 杂志文章
doi:10.1016/j.ejphar.2003.09.034
更新日期:2003-11-28 00:00:00
abstract::Cynaropicrin, a sesquiterpene lactone from Saussurea lappa, has been reported to possess immunomodulatory effects on cytokine release, nitric oxide production and immunosuppressive effects. In this study, we have examined cytotoxic effect of cynaropicrin against several types of cell lines such as macrophages, eosinop...
journal_title:European journal of pharmacology
pub_type: 杂志文章
doi:10.1016/j.ejphar.2004.03.027
更新日期:2004-05-25 00:00:00
abstract::The effects of angiotensin II (AII) and angiotensin III (AIII) on mean arterial pressure (MAP) and mean circulatory filling pressure (MCFP), an index of total body venous tone, in the presence and absence of [Sar1,Ile8]AII in conscious rats were examined. The infusion of AII caused dose-dependent increases in MAP and ...
journal_title:European journal of pharmacology
pub_type: 杂志文章
doi:10.1016/0014-2999(87)90074-4
更新日期:1987-10-27 00:00:00
abstract::The psychotropic actions of crude ginseng saponins, pure ginsenoside Rb1 (GS-Rb1) and ginsenoside Rg1 (GS-Rg1) obtained from the root of Panax ginseng, were evaluated from their effects on agonistic behavior in mice. A resident-intruder test situation was used. When the resident mouse was treated with crude ginseng sa...
journal_title:European journal of pharmacology
pub_type: 杂志文章
doi:10.1016/0014-2999(88)90305-6
更新日期:1988-02-09 00:00:00
abstract::This study was undertaken to define some of the cellular mechanisms of action of serotonin on cerebral vascular muscle. Application of serotonin to cat basilar artery resulted in a dose dependent depolarization and contraction beginning at 10(-8) M. The correlation coefficient relating the degree of force development ...
journal_title:European journal of pharmacology
pub_type: 杂志文章
doi:10.1016/0014-2999(83)90034-1
更新日期:1983-09-16 00:00:00
abstract::Histamine levels are elevated in inflammatory bowel disease. We investigated the mechanism by which histamine affects electrolyte transport in the mouse cecum. Using the Ussing-chamber voltage clamp technique, histamine was found to cause a transient concentration-dependent increase in short-circuit current, a measure...
journal_title:European journal of pharmacology
pub_type: 杂志文章
doi:10.1016/s0014-2999(97)00184-2
更新日期:1997-07-23 00:00:00
abstract::Yawning was recorded from five rhesus monkeys restrained in a chair after i.m. injection of dopaminergic compounds: apomorphine (0.03 mg/kg), quinpirole (0.01 mg/kg), and (-)-3-(3-hydroxyphenyl)-N-(1-propyl)piperidine (1 mg/kg). SKF 38393 or physostigmine produced no yawning. Yawning from apomorphine was blocked by ch...
journal_title:European journal of pharmacology
pub_type: 杂志文章
doi:10.1016/0014-2999(91)90351-p
更新日期:1991-08-29 00:00:00
abstract::Activated microglia that produce reactive nitrogen species (RNS), inflammatory factors, reactive oxygen species (ROS), and other neurovirulent factors may lead to the development of neurodegenerative diseases. Certain compounds can inhibit the activation of microglia. However, these mechanisms remain unclear. In the p...
journal_title:European journal of pharmacology
pub_type: 杂志文章
doi:10.1016/j.ejphar.2016.03.029
更新日期:2016-06-05 00:00:00
abstract::The effects of inhibitors of Ca(2+)-dependent endopeptidases (antipain and leupeptin) on morphine analgesia, reinforcing properties of morphine and on the development of opiate physical dependence were studied. Male Wistar rats were used. The analgesic action of morphine in the tail-immersion test was increased signif...
journal_title:European journal of pharmacology
pub_type: 杂志文章
doi:10.1016/0014-2999(96)00092-1
更新日期:1996-05-23 00:00:00
abstract::Thirty percent of osteosarcoma patients die within 5 years. New agents that induce apoptosis of osteosarcoma cells might be therapeutically useful. Here, we characterized the apoptotic mechanism induced by capsaicin in G292 osteosarcoma cells. Our results show that capsaicin induces an increase in the cytosolic Ca(2+)...
journal_title:European journal of pharmacology
pub_type: 杂志文章
doi:10.1016/j.ejphar.2013.08.011
更新日期:2013-10-15 00:00:00
abstract::To determine the properties of cromakalim-opened K+ channels in arterial smooth muscle of spontaneously hypertensive rats (SHR), the effects of cromakalim on tension and 86Rb efflux were compared in endothelium-denuded strips of carotid arteries from 13-week-old SHR and normotensive Wistar-Kyoto rats (WKY). The additi...
journal_title:European journal of pharmacology
pub_type: 杂志文章
doi:10.1016/0014-2999(94)90532-0
更新日期:1994-09-22 00:00:00
abstract::We have tested for anti-nociceptive effects of the anticonvulsant KCNQ channel opener, N-(2-amino-4-(4-fluorobenzylamino)-phenyl)carbamic acid ethyl ester (retigabine), in rat models of experimental pain. In the chronic constriction injury and spared nerve models of neuropathic pain, injection of retigabine (5 and 20 ...
journal_title:European journal of pharmacology
pub_type: 杂志文章
doi:10.1016/s0014-2999(02)02924-2
更新日期:2003-01-24 00:00:00
abstract::The spontaneous and electrically evoked activity was examined in guinea-pig, ferret and marmoset urinary bladder. Electrical field stimulation of detrusor strips in vitro induced a rapid, frequency-dependent contraction with a maximum response at 40 Hz. This contraction was partly decreased by either atropine (0.29 mi...
journal_title:European journal of pharmacology
pub_type: 杂志文章
doi:10.1016/0014-2999(85)90375-9
更新日期:1985-08-27 00:00:00
abstract::Nicorandil is an adenosine triphosphate-sensitive potassium channel opener with additional antioxidant properties. Doxorubicin (DOX) is an anticancer drug that exerts oxidation-mediated adverse cardiovascular effects. This study examined the effects of nicorandil on DOX-induced cytotoxicity in human umbilical vein end...
journal_title:European journal of pharmacology
pub_type: 杂志文章
doi:10.1016/j.ejphar.2019.172542
更新日期:2019-09-15 00:00:00
abstract::We investigated whether or not insulin and cAMP-elevating agents induce the proliferation of adult rat hepatocytes during the early and late phases of primary culture. Adult rat hepatocytes synthesized a significant amount of DNA when cultured in the presence of 10(-7) M insulin for 3 h. Under these conditions, the nu...
journal_title:European journal of pharmacology
pub_type: 杂志文章
doi:10.1016/s0014-2999(97)89682-3
更新日期:1997-05-26 00:00:00
abstract::FK-33,824 (Tyr-D-Ala-Gly-MePhe-Met(O)-ol) and metkephamid (Tyr-D-Ala-Gly-Phe-N(Me)Met-CONH2; LY 127623) are two parenterally active synthetic analogues of the endogenous morphinomimetic pentapeptide, [Met5]-enkephalin. Acute s.c. administration of each analogue raised the seizure threshold in a dose-related manner in ...
journal_title:European journal of pharmacology
pub_type: 杂志文章
doi:10.1016/0014-2999(81)90392-7
更新日期:1981-04-24 00:00:00
abstract::Berberine, which is a major constituent of the rhizome of Coptidis japonica (CJ), inhibits IL-8 production in colonic epithelial cells and improves 2,4,6-trinitrobenzene sulfonic acid (TNBS)-induced colitis in mice. In our preliminary studies, berberine inhibited lipid peroxidation in liposomes prepared from l-α-phosp...
journal_title:European journal of pharmacology
pub_type: 杂志文章
doi:10.1016/j.ejphar.2010.08.046
更新日期:2010-12-01 00:00:00
abstract::We investigated the effects of acute p.o. pretraining treatment with an indirect acetylcholinesterase inhibitor, metrifonate, on water maze spatial navigation and passive avoidance behavior. Metrifonate (10-100 mg/kg, orally, p.o.) did not improve the water maze or passive avoidance performance of young intact rats. H...
journal_title:European journal of pharmacology
pub_type: 杂志文章
doi:10.1016/0014-2999(96)00336-6
更新日期:1996-08-08 00:00:00
abstract::Stonefish skin secretion contains a smooth muscle relaxant, synancein II, that selectively inhibits tonic responses of KCl-induced contractions of the guinea-pig vas deferens. Synancein II (5-50 micrograms/ml) and nifedipine (10(-8)-10(-7) M) reduced tonic responses equally. Over these concentrations, synancein II inh...
journal_title:European journal of pharmacology
pub_type: 杂志文章
doi:10.1016/0014-2999(86)90341-9
更新日期:1986-09-23 00:00:00
abstract::Nausea and vomiting are common gastrointestinal complaints which could be triggered by stimuli in both the peripheral and central nervous systems. They may be considered as defense mechanisms when threatening toxins/agents enter the gastrointestinal tract or there is excessive retention of gastrointestinal contents du...
journal_title:European journal of pharmacology
pub_type: 杂志文章,评审
doi:10.1016/j.ejphar.2013.09.075
更新日期:2014-01-05 00:00:00
abstract::Dietary fish oils rich in n-3 polyunsaturated fatty acids can modulate a diverse range of factors contributing to cardiovascular disease. This study examined the relative roles of eicosapentaenoic acid (20:5 n-3; EPA) and docosahexaenoic acid (22:6 n-3; DHA) which are the principal n-3 polyunsaturated fatty acids rega...
journal_title:European journal of pharmacology
pub_type: 杂志文章
doi:10.1016/0014-2999(95)00861-6
更新日期:1996-04-04 00:00:00
abstract::Prazosin is believed to have an antihypertensive action due to a selective blockade of alpha-adrenoceptors on vascular smooth muscle. Using an in vitro autoradiographic technique specific binding of [3H]prazosin to the abdominal aorta and renal artery in the rat has been shown. The binding of [3H]prazosin to arterial ...
journal_title:European journal of pharmacology
pub_type: 杂志文章
doi:10.1016/0014-2999(82)90380-6
更新日期:1982-02-19 00:00:00
abstract::The role of leukotriene synthesis in the gastrointestinal damage induced by platelet-activating factor (PAF) was examined in the rat. The effects of a 20-min infusion of PAF (100 ng/kg per min) on leukotriene B4 (LTB4) and leukotriene C4 (LTC4) synthesis were examined in samples of the stomach, duodenum, jejunum, ileu...
journal_title:European journal of pharmacology
pub_type: 杂志文章
doi:10.1016/0014-2999(88)90690-5
更新日期:1988-06-22 00:00:00
abstract::Our previous research showed that ATP and adenosine 5'-O-2-thiodiphosphate (ADPbetaS) induce contractile effects in the longitudinal muscle of mouse distal colon via activation of P2Y receptors which are not P2Y(1) or P2Y(12) subtypes. This study investigated the nature of the P2Y receptor subtype(s) and the mechanism...
journal_title:European journal of pharmacology
pub_type: 杂志文章
doi:10.1016/j.ejphar.2008.07.057
更新日期:2008-10-24 00:00:00