当前位置： SCI文献检索 > EUROPEAN JOURNAL OF PHARMACOLOGY期刊下所有文献 > The selective p38 inhibitor SB-239063 protects primary neurons from mild to moderate excitotoxic injury.

The selective p38 inhibitor SB-239063 protects primary neurons from mild to moderate excitotoxic injury.

Abstract：

:Inhibition of the p38 mitogen-activated protein kinase (MAP Kinase) pathway reduces acute ischemic injury in vivo, suggesting a direct role for this signaling pathway in a number of neurodegenerative processes. The present study was designed to evaluate further the role of p38 MAP Kinase in acute excitotoxic neuronal injury using the selective p38 inhibitor SB-239063 (trans-1-(4hydroxycyclohexyl)-4-(fluorophenyl)-5-(2-methoxy-pyrimidin-4-yl) imidazole). Unlike the widely used p38 inhibitor, SB-203580 (4-(4-Fluorophenyl)-2-(4-methylsulfinylphenyl)-5-(4-pyridyl)1H-imidazole), this second generation p38 inhibitor more selectively inhibits p38 MAP Kinase without affecting the activity of other MAP Kinase signaling pathways and provides a more accurate means to selectively assess the role of p38 in excitotoxicity that has not been previously possible. SB-239063 provided substantial protection against cell death induced by either oxygen glucose deprivation (OGD) or magnesium deprivation in cultured neurons. The ability of this compound to block excitotoxicity was not due to direct inhibition of N-methyl-D-aspartate (NMDA) receptor-mediated currents as SB-239063 did not alter NMDA electrophysiological responses. SB-239063 did not protect against a severe excitotoxic insult induced by 60-min exposure to NMDA. However, when tested against a less severe, brief (5 min) NMDA exposure, p38 inhibition provided substantial protection. These data demonstrate that inhibition of p38 MAP Kinase can confer neuroprotection in vitro against mild but not severe excitotoxic exposure, and suggests that other additional pathways/mechanism(s) may be involved in severe excitotoxic cell death.

journal_name

Eur J Pharmacol

journal_title

European journal of pharmacology

authors

Legos JJ,McLaughlin B,Skaper SD,Strijbos PJ,Parsons AA,Aizenman E,Herin GA,Barone FC,Erhardt JA

doi

10.1016/s0014-2999(02)01890-3

keywords:

subject

Has Abstract

pub_date

2002-06-28 00:00:00

pages

37-42

issue

1

eissn

0014-2999

issn

1879-0712

pii

S0014299902018903

journal_volume

447

pub_type

杂志文章

相关文献

EUROPEAN JOURNAL OF PHARMACOLOGY文献大全
  • Overexpression of SLFN5 induced the epithelial-mesenchymal transition in human lung cancer cell line A549 through β-catenin/Snail/E-cadherin pathway.

    abstract：:Lung cancer is a disease with increasing morbidity worldwide in recent years. Approaches such as chemotherapy and biological targeting for its treatment are urgently needed. Epithelial-mesenchymal transition (EMT) is an important initiation stage for tumor cells to acquire invasive and metastatic abilities. Increasing...

    journal_title：European journal of pharmacology

    pub_type： 杂志文章

    doi：10.1016/j.ejphar.2019.172630

    authors： Guo L,Liu Z,Tang X

    更新日期：2019-11-05 00:00:00

  • L-Arginine supplementation improves insulin sensitivity and beta cell function in the offspring of diabetic rats through AKT and PDX-1 activation.

    abstract：:Maternal hyperglycemia can result in defects in glucose metabolism and pancreatic β-cell function in offspring. The purpose of this study was to evaluate the impact of maternal diabetes mellitus on pancreatic islets, muscle and adipose tissue of the offspring, with or without oral l-Arginine supplementation. The induc...

    journal_title：European journal of pharmacology

    pub_type： 杂志文章

    doi：10.1016/j.ejphar.2016.10.001

    authors： Carvalho DS,Diniz MM,Haidar AA,Cavanal MF,da Silva Alves E,Carpinelli AR,Gil FZ,Hirata AE

    更新日期：2016-11-15 00:00:00

  • Omega-3 polyunsaturated fatty acids--modulation of voltage-dependent L-type Ca2+ current in guinea-pig tracheal smooth muscle cells.

    abstract：:Omega-3 polyunsaturated fatty acids have been reported to be associated with favorable changes in the respiratory system. To determine one of the mechanisms for this effect, membrane currents were recorded in guinea-pig tracheal myocytes by using the whole-cell voltage clamp technique. Without EGTA in the patch pipett...

    journal_title：European journal of pharmacology

    pub_type： 杂志文章

    doi：10.1016/s0014-2999(98)00484-1

    authors： Hazama H,Nakajima T,Asano M,Iwasawa K,Morita T,Igarashi K,Nagata T,Horiuchi T,Suzuki J,Soma M,Okuda Y

    更新日期：1998-08-21 00:00:00

  • Understanding antidepressant discontinuation syndrome (ADS) through preclinical experimental models.

    abstract：:Antidepressant drugs are currently one of the most prescribed medications. In addition to treatment resistance and side effects of antidepressants, their clinical use is further complicated by antidepressant discontinuation syndrome (ADS). ADS is a common problem in patients following the interruption, dose reduction,...

    journal_title：European journal of pharmacology

    pub_type： 杂志文章,评审

    doi：10.1016/j.ejphar.2018.04.003

    authors： Zabegalov KN,Kolesnikova TO,Khatsko SL,Volgin AD,Yakovlev OA,Amstislavskaya TG,Alekseeva PA,Meshalkina DA,Friend AJ,Bao W,Demin KA,Gainetdinov RR,Kalueff AV

    更新日期：2018-06-15 00:00:00

  • The thromboxane A2/prostaglandin endoperoxide receptor antagonist activity of CV-4151, a thromboxane A2 synthetase inhibitor.

    abstract：:The thromboxane A2/prostaglandin endoperoxide (TXA2/PGH2) receptor antagonist activity of CV-4151, a potent TXA2 synthetase inhibitor, was examined. CV-4151 inhibited guinea pig and human platelet aggregation induced by U-44069 with IC50 values of 1.2 +/- 0.3 X 10(-5) and 1.9 +/- 0.4 X 10(-5) M, respectively, and inhi...

    journal_title：European journal of pharmacology

    pub_type： 杂志文章

    doi：10.1016/0014-2999(88)90169-0

    authors： Imura Y,Terashita Z,Shibouta Y,Nishikawa K

    更新日期：1988-03-15 00:00:00

  • Two populations of neurotensin binding sites in murine brain: discrimination by the antihistamine levocabastine reveals markedly different radioautographic distribution.

    abstract：:Monoiodo-[125I-Tyr3]neurotensin (NT) bound to a high affinity, low capacity binding component and a lower affinity, high capacity component in rat brain synaptic membranes. The antihistamine H1 agent levocabastine, which bears no structural relationship to NT, selectively and totally inhibited NT binding to its low af...

    journal_title：European journal of pharmacology

    pub_type： 杂志文章

    doi：10.1016/0014-2999(87)90285-8

    authors： Kitabgi P,Rostène W,Dussaillant M,Schotte A,Laduron PM,Vincent JP

    更新日期：1987-08-21 00:00:00

  • Antidepressant activity of non-competitive and competitive NMDA receptor antagonists in a chronic mild stress model of depression.

    abstract：:The antidepressant properties of the non-competitive NMDA receptor antagonist, MK-801 (dizocilpine), and the competitive NMDA receptor antagonist, CGP 37849 (DL-(E)-2-amino-4-methyl-5-phosphono-3-pentonoic acid) and its (R)-enantiomer CGP 40116, were studied in a chronic mild stress model of depression. In this model,...

    journal_title：European journal of pharmacology

    pub_type： 杂志文章

    doi：10.1016/0014-2999(94)90516-9

    authors： Papp M,Moryl E

    更新日期：1994-09-22 00:00:00

  • A novel anticancer agent Broussoflavonol B downregulates estrogen receptor (ER)-α36 expression and inhibits growth of ER-negative breast cancer MDA-MB-231 cells.

    abstract：:Estrogen receptor (ER)-negative breast cancers are aggressive and unresponsive to antiestrogens, and current therapeutic modalities for ER-negative breast cancer patients are usually associated with strong toxicity and side effects. Less toxic and more effective targeted therapies are urgently needed to treat this typ...

    journal_title：European journal of pharmacology

    pub_type： 杂志文章

    doi：10.1016/j.ejphar.2013.05.047

    authors： Guo M,Wang M,Deng H,Zhang X,Wang ZY

    更新日期：2013-08-15 00:00:00

  • In vitro aggregation facilities beta-amyloid peptide-(25-35)-induced amnesia in the rat.

    abstract：:The beta-amyloid peptide-(25-35) fragment, but not beta-amyloid peptide-(1-28), shares with beta-amyloid protein-(1-42) the ability to self-aggregate and to induce neurotoxicity in vitro. This study examined the induction of amnesia in rats given intracerebroventricularly soluble or aggregated beta-amyloid peptide-(25...

    journal_title：European journal of pharmacology

    pub_type： 杂志文章

    doi：10.1016/s0014-2999(96)00922-3

    authors： Delobette S,Privat A,Maurice T

    更新日期：1997-01-14 00:00:00

  • Involvement of chemical mediators in nasal allergic responses of HDC-KO mice.

    abstract：:The present study was undertaken to investigate the involvement of chemical mediators in nasal allergic responses using histidine decarboxylase knockout (HDC-KO) mice. An allergic rhinitis model was developed in HDC-KO and wild-type mice by the intraperitoneal injection of ovalbumin, aluminum hydroxide gel and pertuss...

    journal_title：European journal of pharmacology

    pub_type： 杂志文章

    doi：10.1016/j.ejphar.2007.01.082

    authors： Rahman MA,Inoue T,Ishikawa T,Yatsuzuka R,Ohtsu H,Kamei C

    更新日期：2007-07-19 00:00:00

  • Proanaphylactic action of morphine is mediated through a central cholinergic mechanism.

    abstract：:Intracerebroventricular (i.c.v.) or intravenous (i.v.) administration of morphine (10 micrograms or 25 mg/kg, respectively) increased the mortality rate in experimental anaphylaxis in mice. This effect was blocked by the opiate antagonist naltrexone administered systemically (5 mg/kg) or i.c.v. (10 micrograms). Moreov...

    journal_title：European journal of pharmacology

    pub_type： 杂志文章

    doi：10.1016/0014-2999(83)90274-1

    authors： Amir S

    更新日期：1983-11-11 00:00:00

  • Antidiabetic effects and sustained metabolic benefits of sub-chronic co-administration of exendin-4/gastrin and xenin-8-Gln in high fat fed mice.

    abstract：:The present study has examined the antidiabetic effects of 21 days co-administration of xenin-8-Gln with the dual-acting fusion peptide, exendin-4/gastrin, as well as persistence of beneficial metabolic benefits, in high fat fed (HFF) mice. Xenin-8-Gln, exendin-4 and gastrin represent compounds that activate receptors...

    journal_title：European journal of pharmacology

    pub_type： 杂志文章

    doi：10.1016/j.ejphar.2019.172733

    authors： Hasib A,Khan D,Craig SL,Gault VA,Flatt PR,Irwin N

    更新日期：2019-12-15 00:00:00

  • [14C]guanidinium ion influx into Na+ channel preparations from mouse cerebral cortex.

    abstract：:[14C]Guanidinium ion influx into Na+ channel preparations from mouse and rat cerebral cortex (purified synaptosomes, and synaptoneurosomes) was characterized and its properties were compared with those for 22Na+ influx. Tetrodotoxin-sensitive influx of [14C]guanidinium ion was stimulated by aconitine, veratridine, and...

    journal_title：European journal of pharmacology

    pub_type： 杂志文章

    doi：10.1016/0922-4106(90)90245-s

    authors： Reith ME

    更新日期：1990-01-23 00:00:00

  • p-Chloroamphetamine, a serotonin-releasing drug, elicited in rats a hyperglycemia mediated by the 5-HT1A and 5-HT2B/2C receptors.

    abstract：:The effects of a serotonin (5-HT) releasing drug, p-chloroamphetamine, on plasma glucose levels were investigated in rats. p-Chloroamphetamine elicited a significant hyperglycemia. The hyperglycemic effects of p-chloroamphetamine were completely prevented by the 5-HT synthesis inhibitor, p-chlorophenylalanine. Prior a...

    journal_title：European journal of pharmacology

    pub_type： 杂志文章

    doi：10.1016/s0014-2999(98)00639-6

    authors： Yamada J,Sugimoto Y,Yoshikawa T

    更新日期：1998-10-23 00:00:00

  • Mu-, delta- and kappa-opioid receptor-mediated inhibition of neurotransmitter release and adenylate cyclase activity in rat brain slices: studies with fentanyl isothiocyanate.

    abstract：:We investigated the effects of [D-Ala2,D-Leu5]enkephalin (DADLE). [D-Ala2,MePhe4,Gly-ol5]enkephalin (DAGO), [D-Pen2,D-Pen5]enkephalin (DPDPE) (0.01-1 microM) and bremazocine (0.001-0.3 microM) on the electrically evoked release of radiolabelled neurotransmitters and on the dopamine (DA)-stimulated cyclic AMP efflux fr...

    journal_title：European journal of pharmacology

    pub_type： 杂志文章

    doi：10.1016/0014-2999(88)90094-5

    authors： Schoffelmeer AN,Rice KC,Jacobson AE,Van Gelderen JG,Hogenboom F,Heijna MH,Mulder AH

    更新日期：1988-09-13 00:00:00

  • Human organic cation transporter 3 mediates the transport of antiarrhythmic drugs.

    abstract：:Antiarrhythmic drugs have been considered to be transported by the organic cation transport system. The purpose of this study was to elucidate the molecular mechanism underlying the transport of antiarrhythmic drugs using cells from the second segment of the proximal tubule (S2) cells of mice expressing human-organic ...

    journal_title：European journal of pharmacology

    pub_type： 杂志文章

    doi：10.1016/j.ejphar.2004.07.098

    authors： Hasannejad H,Takeda M,Narikawa S,Huang XL,Enomoto A,Taki K,Niwa T,Jung SH,Onozato ML,Tojo A,Endou H

    更新日期：2004-09-19 00:00:00

  • Lycopene, quercetin and tyrosol prevent macrophage activation induced by gliadin and IFN-gamma.

    abstract：:Oxidative stress plays an important role in inflammatory process of celiac disease. We have studied the effect of the lycopene, quercetin and tyrosol natural antioxidants on the inducible nitric oxide synthase (iNOS) and cyclooxygenase-2 (COX-2) gene expression in RAW 264.7 macrophages stimulated by gliadin in associa...

    journal_title：European journal of pharmacology

    pub_type： 杂志文章

    doi：10.1016/j.ejphar.2007.03.051

    authors： De Stefano D,Maiuri MC,Simeon V,Grassia G,Soscia A,Cinelli MP,Carnuccio R

    更新日期：2007-07-02 00:00:00

  • ATP induces contraction mediated by the P2Y(2) receptor in rat intestinal subepithelial myofibroblasts.

    abstract：:Intestinal subepithelial myofibroblasts (IMFs) exist just under the epithelial membrane directly facing the mucosal microvascular capillary surface distributed in the lamina propria. In the gastrointestinal tract, ATP is released from epithelial and endothelial cells in response to mechanical stimuli. Although it has ...

    journal_title：European journal of pharmacology

    pub_type： 杂志文章

    doi：10.1016/j.ejphar.2011.01.047

    authors： Nakamura T,Iwanaga K,Murata T,Hori M,Ozaki H

    更新日期：2011-04-25 00:00:00

  • Inhibitors of Ca(2+)-dependent endopeptidases modulate morphine-induced effects in rats.

    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

    authors： Lyupina YV,Sudakov SK,Yarygin VN

    更新日期：1996-05-23 00:00:00

  • Role of RhoA-ROCK signaling in Parkinson's disease.

    abstract：:Parkinson's disease (PD) is a complex and widespread neurodegenerative disease characterized by depletion of midbrain dopaminergic (DA) neurons. Key issues are the development of therapies that can stop or reverse the disease progression, identification of dependable biomarkers, and better understanding of the pathoph...

    journal_title：European journal of pharmacology

    pub_type： 杂志文章,评审

    doi：10.1016/j.ejphar.2020.173815

    authors： Iyer M,Subramaniam MD,Venkatesan D,Cho SG,Ryding M,Meyer M,Vellingiri B

    更新日期：2020-12-17 00:00:00

  • Potential adverse interaction of human cardiac calsequestrin.

    abstract：:Calsequestrin (CASQ) is a major Ca(2+) storage protein within the sarcoplasmic reticulum (SR) of both cardiac and skeletal muscles. CASQ reportedly acts as a Ca(2+) buffer and Ca(2+)-channel regulator through its unique Ca(2+)-dependent oligomerization, maintaining the free Ca(2+) concentration at a low level (0.5-1mM...

    journal_title：European journal of pharmacology

    pub_type： 杂志文章

    doi：10.1016/j.ejphar.2010.08.001

    authors： Kang C,Nissen MS,Sanchez EJ,Lam KS,Milting H

    更新日期：2010-11-10 00:00:00

  • Evidence for purinergic transmission in mouse bladder and for modulation of responses to electrical stimulation by 5-hydroxytryptamine.

    abstract：:Electrical stimulation (ES) contracted superfused mouse bladder, and 10(-7) M tetrodotoxin (TTX) abolished the twitches without impairing responses to acetylcholine (ACh) or beta,gamma-methylene ATP. ES acted largely through nerves which were not cholinergic, adrenergic or histaminergic. They may be purinergic because...

    journal_title：European journal of pharmacology

    pub_type： 杂志文章

    doi：10.1016/0014-2999(85)90190-6

    authors： Holt SE,Cooper M,Wyllie JH

    更新日期：1985-10-08 00:00:00

  • Serotonin-like actions of quipazine and CPP on spinal motoneurones.

    abstract：:The actions of iontophoretically applied quipazine (QPZ) and 6-chloro-2-[1-piperazinyl]-pyrazine (CPP) were compared with those of serotonin (5-HT) on rat spinal motoneurones. QPZ and CPP qualitatively resembled 5-HT in that both facilitated single unit activity evoked by glutamate. Like 5-HT, the facilitation they pr...

    journal_title：European journal of pharmacology

    pub_type： 杂志文章

    doi：10.1016/0014-2999(82)90600-8

    authors： Neuman RS,White SR

    更新日期：1982-06-16 00:00:00

  • Ca2+ release-activated channels in rat stomach smooth muscle cells.

    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

    authors： Smaili SS,Cavalcanti PM,Oshiro ME,Ferreira AT,Jurkiewicz A

    更新日期：1998-01-19 00:00:00

  • Hesperidin reverses cognitive and depressive disturbances induced by olfactory bulbectomy in mice by modulating hippocampal neurotrophins and cytokine levels and acetylcholinesterase activity.

    abstract：:Depression is a serious mental disorder that is becoming more common. To better treat patients suffering from this illness, elucidation of the underlying psychopathological and neurobiological mechanisms of depression is needed. Based on the evidence, we sought to investigate the effects of hesperidin in a model of de...

    journal_title：European journal of pharmacology

    pub_type： 杂志文章

    doi：10.1016/j.ejphar.2016.07.042

    authors： Antunes MS,Jesse CR,Ruff JR,de Oliveira Espinosa D,Gomes NS,Altvater EET,Donato F,Giacomeli R,Boeira SP

    更新日期：2016-10-15 00:00:00

  • Further evaluation of the selectivity of a novel antihypertensive agent, SGB-1534, for peripheral alpha 1-adrenoceptors in the spinally anesthetized dog.

    abstract：:Experiments were designed to examine some characteristics of an orally active antihypertensive agent, SGB-1534 on alpha-adrenoceptors in spinally anesthetized dogs. In the saphenous arterial bed perfused by a constant pump volume, saphenous nerve stimulation and bolus applications of norepinephrine and phenylephrine i...

    journal_title：European journal of pharmacology

    pub_type： 杂志文章

    doi：10.1016/0014-2999(86)90579-0

    authors： Imagawa J,Sakai K

    更新日期：1986-11-19 00:00:00

  • Oleanonic acid, a 3-oxotriterpene from Pistacia, inhibits leukotriene synthesis and has anti-inflammatory activity.

    abstract：:One of the best known bioactive triterpenoids is oleanolic acid, a widespread 3-hydroxy-17-carboxy oleanane-type compound. In order to determine whether further oxidation of carbon 3 affects anti-inflammatory activity in mice, different tests were carried out on oleanolic acid and its 3-oxo-analogue oleanonic acid, wh...

    journal_title：European journal of pharmacology

    pub_type： 杂志文章

    doi：10.1016/s0014-2999(01)01290-0

    authors： Giner-Larza EM,Máñez S,Recio MC,Giner RM,Prieto JM,Cerdá-Nicolás M,Ríos JL

    更新日期：2001-09-28 00:00:00

  • In vivo and in vitro evaluation of novel μ-opioid receptor agonist compounds.

    abstract：:Opioids are the most effective and widely used drugs for pain treatment. Morphine is an archetypal opioid and is an opioid receptor agonist. Unfortunately, the clinical usefulness of morphine is limited by adverse effects such as analgesic tolerance and addiction. Therefore, it is important to study the development of...

    journal_title：European journal of pharmacology

    pub_type： 杂志文章

    doi：10.1016/j.ejphar.2015.10.025

    authors： Nikaido Y,Kurosawa A,Saikawa H,Kuroiwa S,Suzuki C,Kuwabara N,Hoshino H,Obata H,Saito S,Saito T,Osada H,Kobayashi I,Sezutsu H,Takeda S

    更新日期：2015-11-15 00:00:00

  • Epidermal growth factor-induced rapid relaxation of the isolated rabbit mesenteric artery.

    abstract：:Epidermal growth factor (EGF) (10-100 ng ml-1) induced a rapidly developing relaxation of precontracted rabbit mesenteric artery rings within 30 min of exposure. Indomethacin or protein synthesis inhibitors prevented or acutely reversed the effect of EGF on the preparation and an erbstatin analogue significantly reduc...

    journal_title：European journal of pharmacology

    pub_type： 杂志文章

    doi：10.1016/0014-2999(94)90164-3

    authors： Petitclerc E,Poubelle PE,Marceau F

    更新日期：1994-06-23 00:00:00

  • Modification of the peripheral-type benzodiazepine receptor by arachidonate, diethylpyrocarbonate and thiol reagents.

    abstract：:Peripheral type benzodiazepine receptors are differentially modified by arachidonate, diethylpyrocarbonate and thiol reagents, as evidenced by the finding that binding of a proposed agonist ([3H]R05-4864) and a proposed antagonist ([3H]PK 11195) to rat kidney mitochondrial membranes can be modified separately. (1) Ara...

    journal_title：European journal of pharmacology

    pub_type： 杂志文章

    doi：10.1016/0014-2999(87)90454-7

    authors： Skowroński R,Beaumont K,Fanestil DD

    更新日期：1987-11-17 00:00:00