当前位置： SCI文献检索 > MOLECULAR PHARMACOLOGY期刊下所有文献 > Glutamate uptake is inhibited by arachidonic acid and oxygen radicals via two distinct and additive mechanisms.

Glutamate uptake is inhibited by arachidonic acid and oxygen radicals via two distinct and additive mechanisms.

Abstract：

:Reuptake of glutamate in astrocytes, a critical mechanism involved in the maintenance of physiological excitatory amino acid neurotransmission, is inhibited by both arachidonic acid (AA) and reactive oxygen species (ROS), via incompletely defined molecular mechanisms. Because ROS are generated during AA metabolism and AA can be released as a result of ROS-mediated phospholipase A2 activation, it seems likely that their effects on uptake are mediated by a common mechanism. However, here we show that rapid (10-min) uptake inhibitions by AA or by ROS generated by the xanthine plus xanthine oxidase (XO) reaction are selectively abolished by distinct agents; bovine serum albumin (BSA) acts only on AA, whereas the scavenger enzymes superoxide dismutase (SOD) and catalase (CAT) and the disulfide-reducing agent dithiothreitol (DTT) act only on ROS. Moreover, when added together, xanthine/XO and AA decrease uptake in a fully additive manner. In particular, the effect of xanthine/XO is seen also in the presence of maximal AA inhibition. No major signs of cell damage or chemical reaction between AA and radicals accompany their cumulative effects on uptake. Finally, uptake inhibition elicited by AA and xanthine/XO together is attenuated but not blocked by either BSA, DTT, or SOD/CAT individually, whereas it is fully blocked and substantially reversed by a combination of SOD/CAT and BSA or SOD/CAT, DTT, and BSA. Together, these data indicate that AA and ROS act on glial glutamate transport via distinct noninteracting mechanisms. Therefore, they could independently and additively contribute to the impairment of reuptake function, a phenomenon observed in pathological conditions such as ischemia/reperfusion injury.

journal_name

Mol Pharmacol

journal_title

Molecular pharmacology

authors

Volterra A,Trotti D,Racagni G

subject

Has Abstract

pub_date

1994-11-01 00:00:00

pages

986-92

issue

5

eissn

0026-895X

issn

1521-0111

journal_volume

46

pub_type

杂志文章

相关文献

MOLECULAR PHARMACOLOGY文献大全
  • In vitro binding characteristics of a new selective group II metabotropic glutamate receptor radioligand, [3H]LY354740, in rat brain.

    abstract：:The in vitro binding of [3H]LY354740, the first high affinity group II-selective metabotropic glutamate (mGlu) receptor radioligand, was characterized in rat cortical, hippocampal, and thalamic membranes as well as in rat brain sections. [3H]LY354740 binding was saturable in all regions investigated. Nonspecific bindi...

    journal_title：Molecular pharmacology

    pub_type： 杂志文章

    doi：

    authors： Schaffhauser H,Richards JG,Cartmell J,Chaboz S,Kemp JA,Klingelschmidt A,Messer J,Stadler H,Woltering T,Mutel V

    更新日期：1998-02-01 00:00:00

  • Muscarinic modulation of synaptic transmission via endocannabinoid signalling in the rat midbrain periaqueductal gray.

    abstract：:The midbrain periaqueductal gray (PAG) is involved in organizing behavioral responses to threat, stress, and pain. These PAG functions are modulated by cholinergic agents. In the present study, we examined the cholinergic modulation of synaptic transmission in the PAG using whole-cell voltage-clamp recordings from rat...

    journal_title：Molecular pharmacology

    pub_type： 杂志文章

    doi：10.1124/mol.108.045872

    authors： Lau BK,Vaughan CW

    更新日期：2008-11-01 00:00:00

  • Notch1 in Cancer Therapy: Possible Clinical Implications and Challenges.

    abstract：:The Notch family consists of four highly conserved transmembrane receptors. The release of the active intracellular domain requires the enzymatic activity of γ-secretase. Notch is involved in embryonic development and in many physiologic processes of normal cells, in which it regulates growth, apoptosis, and different...

    journal_title：Molecular pharmacology

    pub_type： 杂志文章,评审

    doi：10.1124/molpharm.120.000006

    authors： Gharaibeh L,Elmadany N,Alwosaibai K,Alshaer W

    更新日期：2020-11-01 00:00:00

  • Nonsteroidal human progesterone receptor modulators from the marine alga Cymopolia barbata.

    abstract：:The co-transfection assay is a novel functional assay using cells transiently transfected with plasmids encoding intracellular receptors and corresponding reporter genes. Using this assay, natural product extracts were tested to identify compounds that modulate intracellular receptor activity, measured as changes in r...

    journal_title：Molecular pharmacology

    pub_type： 杂志文章

    doi：

    authors： Pathirana C,Stein RB,Berger TS,Fenical W,Ianiro T,Mais DE,Torres A,Goldman ME

    更新日期：1995-03-01 00:00:00

  • Effects of temperature and membrane phase transitions on ligand binding to alpha 2-receptors of human platelets.

    abstract：:The binding of agonists and antagonists to alpha 2-adrenergic receptors of human platelets was studied. The receptors showed homogeneous affinities for antagonists but two affinity states for the agonist (-)-epinephrine, which were modulated by guanine nucleotides. Van't Hoff plots of antagonist binding had a break po...

    journal_title：Molecular pharmacology

    pub_type： 杂志文章

    doi：

    authors： Lohse MJ,Klotz KN,Schwabe U

    更新日期：1986-03-01 00:00:00

  • Analysis of the four alleles of the murine aryl hydrocarbon receptor.

    abstract：:The cDNAs for the four murine aryl hydrocarbon (Ah) receptor alleles were cloned and sequenced, and the deduced amino acid sequences were compared. The Ahb-1 allele encodes a protein of 805 amino acids, the Ahd and Ahb-2 alleles encode proteins of 848 amino acids, and the Ahb-3 allele encodes a protein of 883 amino ac...

    journal_title：Molecular pharmacology

    pub_type： 杂志文章

    doi：

    authors： Poland A,Palen D,Glover E

    更新日期：1994-11-01 00:00:00

  • Alterations of Histone Modifications Contribute to Pregnane X Receptor-Mediated Induction of CYP3A4 by Rifampicin.

    abstract：:CYP3A4 is one of the major drug-metabolizing enzymes in human and is responsible for the metabolism of 60% of clinically used drugs. Many drugs are able to induce the expression of CYP3A4, which usually causes drug-drug interactions and adverse drug reactions. This study aims to explore the role of histone modificatio...

    journal_title：Molecular pharmacology

    pub_type： 杂志文章

    doi：10.1124/mol.117.108225

    authors： Yan L,Wang Y,Liu J,Nie Y,Zhong XB,Kan Q,Zhang L

    更新日期：2017-08-01 00:00:00

  • Increased biliary GSSG efflux from rat livers perfused with thiocarbamide substrates for the flavin-containing monooxygenase.

    abstract：:Thiourea, phenylthiourea, and methimazole perfused into rat liver stimulated the biliary efflux of GSSG without affecting the excretion of GSH into either the bile or the caval perfusate. The thiocarbamide moiety appears essential, since perfusion with urea, phenylurea, or N-methylimidazole did not stimulate GSSG rele...

    journal_title：Molecular pharmacology

    pub_type： 杂志文章

    doi：

    authors： Krieter PA,Ziegler DM,Hill KE,Burk RF

    更新日期：1984-07-01 00:00:00

  • Novel adamantane derivatives act as blockers of open ligand-gated channels and as anticonvulsants.

    abstract：:We examined the influence of the molecular structure of four novel adamantane derivatives on their ability to block the channels of nicotinic acetylcholine (ACh) and N-methyl-D-aspartate (NMDA) receptors. The structure of the drugs is Ad-CH2-N+H2-(CH2)5-R, where Ad is adamantane and R was varied from ammonium (IEM-175...

    journal_title：Molecular pharmacology

    pub_type： 杂志文章

    doi：

    authors： Antonov SM,Johnson JW,Lukomskaya NY,Potapyeva NN,Gmiro VE,Magazanik LG

    更新日期：1995-03-01 00:00:00

  • Alteration in accumulated aldosterone synthesis as a result of N-terminal cleavage of aldosterone synthase.

    abstract：:Aldosterone synthase (AS) regulates blood volume by synthesizing the mineralocorticoid aldosterone. Overproduction of aldosterone in the adrenal gland can lead to hypertension, a major cause of heart disease and stroke. Aldosterone production depends upon stimulation of AS expression by the renin-angiotensin system, w...

    journal_title：Molecular pharmacology

    pub_type： 杂志文章

    doi：10.1124/mol.111.076471

    authors： Adams BP,Bose HS

    更新日期：2012-03-01 00:00:00

  • Orientation of the heterodimeric aryl hydrocarbon (dioxin) receptor complex on its asymmetric DNA recognition sequence.

    abstract：:The 2,3,7,8-tetrachlorodibenzo-p-dioxin-transformed aryl hydrocarbon receptor (AHR) complex binds to xenobiotic-responsive element (XRE) sequences in the 5' flanking region of the CYP1A1 gene, resulting in initiation of transcription. Both components of the transformed AHR complex [the ligand-binding AHR monomer and t...

    journal_title：Molecular pharmacology

    pub_type： 杂志文章

    doi：

    authors： Bacsi SG,Reisz-Porszasz S,Hankinson O

    更新日期：1995-03-01 00:00:00

  • Transcriptional regulation of mouse mu opioid receptor gene: Sp3 isoforms (M1, M2) function as repressors in neuronal cells to regulate the mu opioid receptor gene.

    abstract：:The 5'-flanking region of the mouse mu opioid receptor (MOR) gene has two promoters, referred to as distal and proximal. MOR mRNA is predominantly initiated by the proximal promoter. Previously, several important cis-elements and trans-factors have been shown to play a functional role in the proximal promoter of the M...

    journal_title：Molecular pharmacology

    pub_type： 杂志文章

    doi：10.1124/mol.104.008284

    authors： Choi HS,Hwang CK,Kim CS,Song KY,Law PY,Wei LN,Loh HH

    更新日期：2005-05-01 00:00:00

  • 2,3,7,8-Tetrachlorodibenzo-p-dioxin suppresses tumor necrosis factor-alpha and anti-CD40-induced activation of NF-kappaB/Rel in dendritic cells: p50 homodimer activation is not affected.

    abstract：:2,3,7,8-Tetrachlorodibenzo-p-dioxin (TCDD) suppresses many immune responses, both innate and adaptive. Suppression is mediated by the aryl hydrocarbon receptor (AhR), a ligand-activated transcription factor. The AhR mediates TCDD toxicity presumably through the alteration of transcriptional events, either by promoting...

    journal_title：Molecular pharmacology

    pub_type： 杂志文章

    doi：10.1124/mol.62.3.722

    authors： Ruby CE,Leid M,Kerkvliet NI

    更新日期：2002-09-01 00:00:00

  • Ligand binding and kinetics of folate receptor recycling in vivo: impact on receptor-mediated drug delivery.

    abstract：:Folate receptor-targeted cancer therapies constitute a promising treatment for the approximately one third of human cancers that overexpress the folate receptor (FR). However, the potencies of all folate-receptor targeted therapies depend on 1) the rate of folate-linked drug conjugate binding to the cancer cell surfac...

    journal_title：Molecular pharmacology

    pub_type： 杂志文章

    doi：10.1124/mol.104.003723

    authors： Paulos CM,Reddy JA,Leamon CP,Turk MJ,Low PS

    更新日期：2004-12-01 00:00:00

  • S-nitrosylating agents: a novel class of compounds that increase cystic fibrosis transmembrane conductance regulator expression and maturation in epithelial cells.

    abstract：:The endogenous bronchodilator, S-nitrosoglutathione (GSNO), increases expression, maturation, and function of both the wild-type and the DeltaF508 mutant of the cystic fibrosis transmembrane conductance regulatory protein (CFTR). Though transcriptional mechanisms of action have been identified, GSNO seems also to have...

    journal_title：Molecular pharmacology

    pub_type： 杂志文章

    doi：10.1124/mol.106.023242

    authors： Zaman K,Carraro S,Doherty J,Henderson EM,Lendermon E,Liu L,Verghese G,Zigler M,Ross M,Park E,Palmer LA,Doctor A,Stamler JS,Gaston B

    更新日期：2006-10-01 00:00:00

  • Modeling and Mutational Analysis of the Binding Mode for the Multimodal Antidepressant Drug Vortioxetine to the Human 5-HT3A Receptor.

    abstract：:5-Hydroxytryptamine3 (5-HT3) receptors are ligand-gated ion channels that mediate neurotransmission by serotonin in the central nervous system. Pharmacological inhibition of 5-HT3 receptor activity has therapeutic potential in several psychiatric diseases, including depression and anxiety. The recently approved multim...

    journal_title：Molecular pharmacology

    pub_type： 杂志文章

    doi：10.1124/mol.118.113530

    authors： Ladefoged LK,Munro L,Pedersen AJ,Lummis SCR,Bang-Andersen B,Balle T,Schiøtt B,Kristensen AS

    更新日期：2018-12-01 00:00:00

  • Low concentrations of vinflunine induce apoptosis in human SK-N-SH neuroblastoma cells through a postmitotic G1 arrest and a mitochondrial pathway.

    abstract：:Vinflunine, the newest fluorinated Vinca alkaloid, currently in phase III clinical trials, targets the microtubule network to induce mitotic block and apoptosis by mechanisms that remain unclear. In the current study, we investigated the apoptotic pathways induced by a wide range of vinflunine concentrations in SK-N-S...

    journal_title：Molecular pharmacology

    pub_type： 杂志文章

    doi：10.1124/mol.66.3.

    authors： Pourroy B,Carré M,Honoré S,Bourgarel-Rey V,Kruczynski A,Briand C,Braguer D

    更新日期：2004-09-01 00:00:00

  • Effect of avermectin B1a on chick neuronal gamma-aminobutyrate receptor channels expressed in Xenopus oocytes.

    abstract：:Chick brain mRNA was isolated and injected into Xenopus oocytes. This led to the expression of gamma-aminobutyrate (GABA) channels easily accessible for current measurements using the voltage clamp technique. The effect of the anthelmintic natural product avermectin B1a on the GABA current was studied quantitatively. ...

    journal_title：Molecular pharmacology

    pub_type： 杂志文章

    doi：

    authors： Sigel E,Baur R

    更新日期：1987-12-01 00:00:00

  • RGS14, a GTPase-activating protein for Gialpha, attenuates Gialpha- and G13alpha-mediated signaling pathways.

    abstract：:Regulator of G protein signaling (RGS) proteins are a family of approximately 20 proteins that negatively regulate signaling through heterotrimeric G protein-coupled receptors. The RGS proteins act as GTPase-activating proteins (GAPs) for certain Galpha subunits and as effector antagonists for Gqalpha. Mouse RGS14 enc...

    journal_title：Molecular pharmacology

    pub_type： 杂志文章

    doi：10.1124/mol.58.3.569

    authors： Cho H,Kozasa T,Takekoshi K,De Gunzburg J,Kehrl JH

    更新日期：2000-09-01 00:00:00

  • Cloning and expression of a human metabotropic glutamate receptor 1 alpha: enhanced coupling on co-transfection with a glutamate transporter.

    abstract：:We cloned and expressed a human metabotropic glutamate receptor 1 alpha (HmGluR1 alpha) in a novel cell line. The human mGluR1 alpha cDNA was found to be 86% identical to rat mGluR1 alpha, and the predicted protein sequence was found to be 93% identical to rat mGluR1 alpha. We expressed HmGluR1 alpha in AV12-664, an a...

    journal_title：Molecular pharmacology

    pub_type： 杂志文章

    doi：

    authors： Desai MA,Burnett JP,Mayne NG,Schoepp DD

    更新日期：1995-10-01 00:00:00

  • Are alpha9alpha10 nicotinic acetylcholine receptors a pain target for alpha-conotoxins?

    abstract：:The synthetic alpha-conotoxin Vc1.1 is a small disulfide bonded peptide currently in development as a treatment for neuropathic pain. Unlike Vc1.1, the native post-translationally modified peptide vc1a does not act as an analgesic in vivo in rat models of neuropathic pain. It has recently been proposed that the primar...

    journal_title：Molecular pharmacology

    pub_type： 杂志文章

    doi：10.1124/mol.107.040568

    authors： Nevin ST,Clark RJ,Klimis H,Christie MJ,Craik DJ,Adams DJ

    更新日期：2007-12-01 00:00:00

  • Mitochondria, calcium, and calpain are key mediators of resveratrol-induced apoptosis in breast cancer.

    abstract：:Resveratrol (RES), a natural plant polyphenol, has gained interest as a nontoxic chemopreventive agent capable of inducing tumor cell death in a variety of cancer types. However, the early molecular mechanisms of RES-induced apoptosis are not well defined. Using the human breast cancer cell lines MDA-MB-231 and MCF-7,...

    journal_title：Molecular pharmacology

    pub_type： 杂志文章

    doi：10.1124/mol.107.039040

    authors： Sareen D,Darjatmoko SR,Albert DM,Polans AS

    更新日期：2007-12-01 00:00:00

  • Comparison of two putatively selective radioligands for labeling central nervous system beta-adrenergic receptors: inadequacy of [3H]dihydroalprenolol.

    abstract：:[3H]Dihydroalprenolol ([3H]DHA) has been used extensively in receptor binding studies to measure beta-adrenergic receptors in the central nervous system. Usually, nonspecific binding has been defined by high concentrations of the beta-adrenergic receptor agonist isoproterenol or antagonists such as alprenolol or propr...

    journal_title：Molecular pharmacology

    pub_type： 杂志文章

    doi：

    authors： Riva MA,Creese I

    更新日期：1989-07-01 00:00:00

  • Vasoactive intestinal polypeptide facilitates tyrosine hydroxylase induction by cholinergic agonists in bovine adrenal chromaffin cells.

    abstract：:The possibility that vasoactive intestinal polypeptide (VIP) may facilitate the nicotine-mediated induction of adrenal medullary tyrosine hydroxylase (TH) was investigated with primary cultures (5-7 days in vitro) of bovine adrenal chromaffin (BAC) cells. Exposure of BAC cells to 100 microM nicotine led to only a marg...

    journal_title：Molecular pharmacology

    pub_type： 杂志文章

    doi：

    authors： Olasmaa M,Guidotti A,Costa E

    更新日期：1992-03-01 00:00:00

  • Identification of the multidrug resistance-related P-glycoprotein as a cyclosporine binding protein.

    abstract：:The immunosuppressive agent cyclosporine A has been shown to reverse multidrug resistance (MDR) in malignant cells. In the present study, a 3H-cyclosporine diazirine analogue was used to photolabel viable MDR Chinese hamster ovary cells. The 170-kDa membrane P-glycoprotein, which functions as a drug efflux pump, was s...

    journal_title：Molecular pharmacology

    pub_type： 杂志文章

    doi：

    authors： Foxwell BM,Mackie A,Ling V,Ryffel B

    更新日期：1989-10-01 00:00:00

  • Mutations in the main cytoplasmic loop of the GABA(A) receptor α4 and δ subunits have opposite effects on surface expression.

    abstract：:We examined the role of putative trafficking sequences in two GABA(A) receptor subunits: α4 and δ. These subunits assemble with a β subunit to form a subtype of GABA(A) receptor involved in generating the "tonic" outward current. Both α4 and δ subunits contain dibasic retention motifs in homologous positions. When bas...

    journal_title：Molecular pharmacology

    pub_type： 杂志文章

    doi：10.1124/mol.114.092791

    authors： Bracamontes JR,Li P,Akk G,Steinbach JH

    更新日期：2014-07-01 00:00:00

  • ORKAMBI-Mediated Rescue of Mucociliary Clearance in Cystic Fibrosis Primary Respiratory Cultures Is Enhanced by Arginine Uptake, Arginase Inhibition, and Promotion of Nitric Oxide Signaling to the Cystic Fibrosis Transmembrane Conductance Regulator Channe

    abstract：:ORKAMBI, a combination of the corrector, lumacaftor, and the potentiator, ivacaftor, partially rescues the defective processing and anion channel activity conferred by the major cystic fibrosis-causing mutation, F508del, in in vitro studies. Clinically, the improvement in lung function after ORKAMBI treatment is modes...

    journal_title：Molecular pharmacology

    pub_type： 杂志文章

    doi：10.1124/mol.119.117143

    authors： Wu YS,Jiang J,Ahmadi S,Lew A,Laselva O,Xia S,Bartlett C,Ip W,Wellhauser L,Ouyang H,Gonska T,Moraes TJ,Bear CE

    更新日期：2019-10-01 00:00:00

  • The role of the seventh transmembrane region in high affinity binding of a beta 2-selective agonist TA-2005.

    abstract：:To determine the structural basis for binding subtype selective agonists in the beta-adrenergic receptor (beta AR), we examined the interaction of the mutant beta 2AR and chimeric beta 1/beta 2AR with a selective beta 2AR agonist, TA-2005 (8-hydroxy-5-[(1R)-1-hydroxy-2-[N-[(1R)-2-(p-methoxyphenyl)-1-methyle thy l] am...

    journal_title：Molecular pharmacology

    pub_type： 杂志文章

    doi：10.1124/mol.53.1.128

    authors： Kikkawa H,Isogaya M,Nagao T,Kurose H

    更新日期：1998-01-01 00:00:00

  • Palmitoylation of the 5-hydroxytryptamine4a receptor regulates receptor phosphorylation, desensitization, and beta-arrestin-mediated endocytosis.

    abstract：:The mouse 5-hydroxytryptamine4a (5-HT4a) receptor is an unusual member of the G protein-coupled receptor superfamily because it possesses two separate carboxyl-terminal palmitoylation sites, which may allow the receptor to adopt different conformations in an agonist-dependent manner (J Biol Chem 277:2534-2546, 2002). ...

    journal_title：Molecular pharmacology

    pub_type： 杂志文章

    doi：10.1124/mol.104.008748

    authors： Ponimaskin E,Dumuis A,Gaven F,Barthet G,Heine M,Glebov K,Richter DW,Oppermann M

    更新日期：2005-05-01 00:00:00

  • Inactivation and biotransformation of the endogenous cannabinoids anandamide and 2-arachidonoylglycerol.

    abstract：:The cannabinoid field is currently an active research area. Anandamide (AEA) and 2-arachidonoylglycerol (2-AG) are the most characterized endogenous cannabinoids (also known as endocannabinoids). These neuromodulators have been implicated in various physiologically relevant phenomena, including mood (Witkin et al., 20...

    journal_title：Molecular pharmacology

    pub_type： 杂志文章,评审

    doi：10.1124/mol.109.055251

    authors： Yates ML,Barker EL

    更新日期：2009-07-01 00:00:00