Activation of 5-HT2A receptors upregulates the function of the neuronal K-Cl cotransporter KCC2.

Abstract:

:In healthy adults, activation of γ-aminobutyric acid (GABA)(A) and glycine receptors inhibits neurons as a result of low intracellular chloride concentration ([Cl(-)](i)), which is maintained by the potassium-chloride cotransporter KCC2. A reduction of KCC2 expression or function is implicated in the pathogenesis of several neurological disorders, including spasticity and chronic pain following spinal cord injury (SCI). Given the critical role of KCC2 in regulating the strength and robustness of inhibition, identifying tools that may increase KCC2 function and, hence, restore endogenous inhibition in pathological conditions is of particular importance. We show that activation of 5-hydroxytryptamine (5-HT) type 2A receptors to serotonin hyperpolarizes the reversal potential of inhibitory postsynaptic potentials (IPSPs), E(IPSP), in spinal motoneurons, increases the cell membrane expression of KCC2 and both restores endogenous inhibition and reduces spasticity after SCI in rats. Up-regulation of KCC2 function by targeting 5-HT(2A) receptors, therefore, has therapeutic potential in the treatment of neurological disorders involving altered chloride homeostasis. However, these receptors have been implicated in several psychiatric disorders, and their effects on pain processing are controversial, highlighting the need to further investigate the potential systemic effects of specific 5-HT(2A)R agonists, such as (4-bromo-3,6-dimethoxybenzocyclobuten-1-yl)methylamine hydrobromide (TCB-2).

authors

Bos R,Sadlaoud K,Boulenguez P,Buttigieg D,Liabeuf S,Brocard C,Haase G,Bras H,Vinay L

doi

10.1073/pnas.1213680110

subject

Has Abstract

pub_date

2013-01-02 00:00:00

pages

348-53

issue

1

eissn

0027-8424

issn

1091-6490

pii

1213680110

journal_volume

110

pub_type

杂志文章
  • Association mapping of local climate-sensitive quantitative trait loci in Arabidopsis thaliana.

    abstract::Flowering time (FT) is the developmental transition coupling an internal genetic program with external local and seasonal climate cues. The genetic loci sensitive to predictable environmental signals underlie local adaptation. We dissected natural variation in FT across a new global diversity set of 473 unique accessi...

    journal_title:Proceedings of the National Academy of Sciences of the United States of America

    pub_type: 杂志文章

    doi:10.1073/pnas.1007431107

    authors: Li Y,Huang Y,Bergelson J,Nordborg M,Borevitz JO

    更新日期:2010-12-07 00:00:00

  • Estimating enhanced prevaccination measles transmission hotspots in the context of cross-scale dynamics.

    abstract::A key question in clarifying human-environment interactions is how dynamic complexity develops across integrative scales from molecular to population and global levels. Apart from its public health importance, measles is an excellent test bed for such an analysis. Simple mechanistic models have successfully illuminate...

    journal_title:Proceedings of the National Academy of Sciences of the United States of America

    pub_type: 历史文章,杂志文章

    doi:10.1073/pnas.1604976113

    authors: Becker AD,Birger RB,Teillant A,Gastanaduy PA,Wallace GS,Grenfell BT

    更新日期:2016-12-20 00:00:00

  • Alleles of the Ly-17 alloantigen define polymorphisms of the murine IgG Fc receptor.

    abstract::Antibodies specific for allelic determinants of the cell membrane alloantigen Ly-17 were found to react with genetically determined polymorphic sites on the murine IgG Fc receptor (Fc gamma R). Monoclonal antibodies specific for Ly-17.2 and the Fc gamma R detected identical populations of cells in thymus, spleen, lymp...

    journal_title:Proceedings of the National Academy of Sciences of the United States of America

    pub_type: 杂志文章

    doi:10.1073/pnas.82.22.7706

    authors: Holmes KL,Palfree RG,Hammerling U,Morse HC 3rd

    更新日期:1985-11-01 00:00:00

  • Geometric derivation of the chronometric redshift.

    abstract::The chronometric redshift-distance relation z = tan 2(1/2rho), where rho is the distance in radians in the Einstein metric, is derived by an elementary geometric analysis comparable to that in traditional analysis of the expanding universe model. The differential dTt of Einstein time evolution Tt through time t, as ap...

    journal_title:Proceedings of the National Academy of Sciences of the United States of America

    pub_type: 杂志文章

    doi:10.1073/pnas.90.23.11114

    authors: Segal IE

    更新日期:1993-12-01 00:00:00

  • gamma-Aminobutyric acid antagonists decrease junctional communication between L-horizontal cells of the retina.

    abstract::The antagonists of gamma-aminobutyric acid, bicuculline and picrotoxin, were found to narrow the receptive field profile of the large field horizontal cell (L1HC) in the turtle retina when added to the perfusion medium in micromolar concentrations. The coupling resistance between neighboring L1HCs was increased by bic...

    journal_title:Proceedings of the National Academy of Sciences of the United States of America

    pub_type: 杂志文章

    doi:10.1073/pnas.79.11.3671

    authors: Piccolino M,Neyton J,Witkovsky P,Gerschenfeld HM

    更新日期:1982-06-01 00:00:00

  • Dynamics of a protein matrix revealed by fluorescence quenching.

    abstract::The fluorescence of the supposedly buried tryptophan in ribonuclease T1 has been found to be collisionally quenched by acrylamide with a rate constant of 3 X 10(8) M--1 sec--1. Only a slight decrease in the quenching rate is observed upon a 5-fold increase in the viscosity of the solution. For this to be the case, the...

    journal_title:Proceedings of the National Academy of Sciences of the United States of America

    pub_type: 杂志文章

    doi:10.1073/pnas.72.9.3290

    authors: Eftink MR,Ghiron CA

    更新日期:1975-09-01 00:00:00

  • Unexpected NO-dependent DNA binding by the CooA homolog from Carboxydothermus hydrogenoformans.

    abstract::CooA, the CO-sensing heme protein from Rhodospirillum rubrum, regulates the expression of genes that encode a CO-oxidation system, allowing R. rubrum to use CO as a sole energy source. To better understand the gas-sensing regulation mechanism used by R. rubrum CooA and its homologs in other organisms, we characterized...

    journal_title:Proceedings of the National Academy of Sciences of the United States of America

    pub_type: 杂志文章

    doi:10.1073/pnas.0505919103

    authors: Clark RW,Lanz ND,Lee AJ,Kerby RL,Roberts GP,Burstyn JN

    更新日期:2006-01-24 00:00:00

  • The contribution of epistasis to the architecture of fitness in an RNA virus.

    abstract::The tendency for genetic architectures to exhibit epistasis among mutations plays a central role in the modern synthesis of evolutionary biology and in theoretical descriptions of many evolutionary processes. Nevertheless, few studies unquestionably show whether, and how, mutations typically interact. Beneficial mutat...

    journal_title:Proceedings of the National Academy of Sciences of the United States of America

    pub_type: 杂志文章

    doi:10.1073/pnas.0404125101

    authors: Sanjuán R,Moya A,Elena SF

    更新日期:2004-10-26 00:00:00

  • Conserved mechanism for coordinating replication fork helicase assembly with phosphorylation of the helicase.

    abstract::Dbf4-dependent kinase (DDK) phosphorylates minichromosome maintenance 2 (Mcm2) during S phase in yeast, and Sld3 recruits cell division cycle 45 (Cdc45) to minichromosome maintenance 2-7 (Mcm2-7). We show here DDK-phosphoryled Mcm2 preferentially interacts with Cdc45 in vivo, and that Sld3 stimulates DDK phosphorylati...

    journal_title:Proceedings of the National Academy of Sciences of the United States of America

    pub_type: 杂志文章

    doi:10.1073/pnas.1509608112

    authors: Bruck I,Kaplan DL

    更新日期:2015-09-08 00:00:00

  • Identification of genes that synergize with Cbfb-MYH11 in the pathogenesis of acute myeloid leukemia.

    abstract::Acute myeloid leukemia subtype M4 with eosinophilia is associated with a chromosome 16 inversion that creates a fusion gene CBFB-MYH11. We have previously shown that CBFB-MYH11 is necessary but not sufficient for leukemogenesis. Here, we report the identification of genes that specifically cooperate with CBFB-MYH11 in...

    journal_title:Proceedings of the National Academy of Sciences of the United States of America

    pub_type: 杂志文章

    doi:10.1073/pnas.0400930101

    authors: Castilla LH,Perrat P,Martinez NJ,Landrette SF,Keys R,Oikemus S,Flanegan J,Heilman S,Garrett L,Dutra A,Anderson S,Pihan GA,Wolff L,Liu PP

    更新日期:2004-04-06 00:00:00

  • Molecular immune responses of the mosquito Anopheles gambiae to bacteria and malaria parasites.

    abstract::Immune responses of the malaria vector mosquito Anopheles gambiae were monitored systematically by the induced expression of five RNA markers after infection challenge. One newly isolated marker encodes a homologue of the moth Gram-negative bacteria-binding protein (GNBP), and another corresponds to a serine protease-...

    journal_title:Proceedings of the National Academy of Sciences of the United States of America

    pub_type: 杂志文章

    doi:10.1073/pnas.94.21.11508

    authors: Dimopoulos G,Richman A,Müller HM,Kafatos FC

    更新日期:1997-10-14 00:00:00

  • Stage-specific predator species help each other to persist while competing for a single prey.

    abstract::Prey in natural communities are usually shared by many predator species. How predators coexist while competing for the same prey is one of the fundamental questions in ecology. Here, we show that competing predator species may not only coexist on a single prey but even help each other to persist if they specialize on ...

    journal_title:Proceedings of the National Academy of Sciences of the United States of America

    pub_type: 杂志文章

    doi:10.1073/pnas.0803834105

    authors: De Roos AM,Schellekens T,Van Kooten T,Persson L

    更新日期:2008-09-16 00:00:00

  • Biosynthesis of the enediyne antitumor antibiotic C-1027 involves a new branching point in chorismate metabolism.

    abstract::C-1027 is an enediyne antitumor antibiotic composed of four distinct moieties: an enediyne core, a deoxy aminosugar, a beta-amino acid, and a benzoxazolinate moiety. We now show that the benzoxazolinate moiety is derived from chorismate by the sequential action of two enzymes-SgcD, a 2-amino-2-deoxyisochorismate (ADIC...

    journal_title:Proceedings of the National Academy of Sciences of the United States of America

    pub_type: 杂志文章

    doi:10.1073/pnas.0708750105

    authors: Van Lanen SG,Lin S,Shen B

    更新日期:2008-01-15 00:00:00

  • HLA-linked congenital adrenal hyperplasia results from a defective gene encoding a cytochrome P-450 specific for steroid 21-hydroxylation.

    abstract::We have determined the molecular genetic basis of congenital adrenal hyperplasia due to 21-hydroxylase (21-OHase) deficiency. This common disorder of cortisol biosynthesis is HLA-linked. The haplotype HLA-(A3);Bw47;DR7 is strongly associated with 21-OHase deficiency and always carries a null allele at the locus encodi...

    journal_title:Proceedings of the National Academy of Sciences of the United States of America

    pub_type: 杂志文章

    doi:10.1073/pnas.81.23.7505

    authors: White PC,New MI,Dupont B

    更新日期:1984-12-01 00:00:00

  • RNA polymerase-associated transcription specificity factor encoded by vaccinia virus.

    abstract::Vaccinia virus encodes a multisubunit DNA-dependent RNA polymerase (EC 2.7.7.6) that is packaged in the infectious virus particle. This polymerase was found to contain a submolar polypeptide of approximately 85 kDa in addition to the core subunits, which consist of two larger and several smaller polypeptides. The poly...

    journal_title:Proceedings of the National Academy of Sciences of the United States of America

    pub_type: 杂志文章

    doi:10.1073/pnas.89.8.3536

    authors: Ahn BY,Moss B

    更新日期:1992-04-15 00:00:00

  • TMEM203 is a binding partner and regulator of STING-mediated inflammatory signaling in macrophages.

    abstract::Regulation of IFN signaling is critical in host recognition and response to pathogens while its dysregulation underlies the pathogenesis of several chronic diseases. STimulator of IFN Genes (STING) has been identified as a critical mediator of IFN inducing innate immune pathways, but little is known about direct coreg...

    journal_title:Proceedings of the National Academy of Sciences of the United States of America

    pub_type: 杂志文章

    doi:10.1073/pnas.1901090116

    authors: Li Y,James SJ,Wyllie DH,Wynne C,Czibula A,Bukhari A,Pye K,Bte Mustafah SM,Fajka-Boja R,Szabo E,Angyal A,Hegedus Z,Kovacs L,Hill AVS,Jefferies CA,Wilson HL,Yongliang Z,Kiss-Toth E

    更新日期:2019-08-13 00:00:00

  • The ionic layer is required for efficient dissociation of the SNARE complex by alpha-SNAP and NSF.

    abstract::The four-helical bundle soluble N-ethylmaleimide-sensitive fusion protein (NSF) attachment protein receptor (SNARE) complex that mediates intracellular membrane fusion events contains a highly conserved ionic layer at the center of an otherwise hydrophobic core. This layer has an undetermined function; it consists of ...

    journal_title:Proceedings of the National Academy of Sciences of the United States of America

    pub_type: 杂志文章

    doi:10.1073/pnas.251547598

    authors: Scales SJ,Yoo BY,Scheller RH

    更新日期:2001-12-04 00:00:00

  • Inhibition of RNA polymerase II transcription in human cells by synthetic DNA-binding ligands.

    abstract::Sequence-specific DNA-binding small molecules that can permeate human cells potentially could regulate transcription of specific genes. Multiple cellular DNA-binding transcription factors are required by HIV type 1 for RNA synthesis. Two pyrrole-imidazole polyamides were designed to bind DNA sequences immediately adja...

    journal_title:Proceedings of the National Academy of Sciences of the United States of America

    pub_type: 杂志文章

    doi:10.1073/pnas.95.22.12890

    authors: Dickinson LA,Gulizia RJ,Trauger JW,Baird EE,Mosier DE,Gottesfeld JM,Dervan PB

    更新日期:1998-10-27 00:00:00

  • Single-step selection of clones of a mouse hepatoma line deficient in aryl hydrocarbon hydroxylase.

    abstract::The mouse hepatoma line Hepa-1 has high and inducible aryl hydrocarbon (benzo[a]pyrene) hydroxylase[benzo[a]pyrene, reduced-flavoprotein:oxygen oxidoreductase (3-hydroxylating), EC 1.14.14.2] activity. Fourteen subclones of a clonal derivative of Hepa-1 were isolated and shown not to display heterogeneity in aryl hydr...

    journal_title:Proceedings of the National Academy of Sciences of the United States of America

    pub_type: 杂志文章

    doi:10.1073/pnas.76.1.373

    authors: Hankinson O

    更新日期:1979-01-01 00:00:00

  • High-throughput patterning of photonic structures with tunable periodicity.

    abstract::A patterning method termed "RIPPLE" (reactive interface patterning promoted by lithographic electrochemistry) is applied to the fabrication of arrays of dielectric and metallic optical elements. This method uses cyclic voltammetry to impart patterns onto the working electrode of a standard three-electrode electrochemi...

    journal_title:Proceedings of the National Academy of Sciences of the United States of America

    pub_type: 杂志文章

    doi:10.1073/pnas.1504280112

    authors: Kempa TJ,Bediako DK,Kim SK,Park HG,Nocera DG

    更新日期:2015-04-28 00:00:00

  • Cell density and mobility protect swarming bacteria against antibiotics.

    abstract::Swarming bacteria move in multicellular groups and exhibit adaptive resistance to multiple antibiotics. Analysis of this phenomenon has revealed the protective power of high cell densities to withstand exposure to otherwise lethal antibiotic concentrations. We find that high densities promote bacterial survival, even ...

    journal_title:Proceedings of the National Academy of Sciences of the United States of America

    pub_type: 杂志文章

    doi:10.1073/pnas.0910934107

    authors: Butler MT,Wang Q,Harshey RM

    更新日期:2010-02-23 00:00:00

  • Refined crystal structure of DsRed, a red fluorescent protein from coral, at 2.0-A resolution.

    abstract::The crystal structure of DsRed, a red fluorescent protein from a corallimorpharian, has been determined at 2.0-A resolution by multiple-wavelength anomalous dispersion and crystallographic refinement. Crystals of the selenomethionine-substituted protein have space group P2(1) and contain a tetramer with 222 noncrystal...

    journal_title:Proceedings of the National Academy of Sciences of the United States of America

    pub_type: 杂志文章

    doi:10.1073/pnas.98.2.462

    authors: Yarbrough D,Wachter RM,Kallio K,Matz MV,Remington SJ

    更新日期:2001-01-16 00:00:00

  • Physiologically relevant and portable tandem ubiquitin-binding domain stabilizes polyubiquitylated proteins.

    abstract::Ubiquitylation of proteins can be a signal for a variety of cellular processes beyond the classical role in proteolysis. The different signaling functions of ubiquitylation are thought to rely on ubiquitin-binding domains (UBDs). Several distinct UBD families are known, but their functions are not understood in detail...

    journal_title:Proceedings of the National Academy of Sciences of the United States of America

    pub_type: 杂志文章

    doi:10.1073/pnas.1010648107

    authors: Tyrrell A,Flick K,Kleiger G,Zhang H,Deshaies RJ,Kaiser P

    更新日期:2010-11-16 00:00:00

  • The peptide-catalyzed stereospecific synthesis of tetroses: a possible model for prebiotic molecular evolution.

    abstract::Using a water-based prebiotic model of sugar synthesis involving glycolaldehyde self-condensation, we demonstrate that homochiral L-dipeptide catalysts lead to the stereospecific syntheses of tetroses. The asymmetric effect is largest for erythrose, which may reach a D-enantiomeric excess of >80% with L-Val-L-Val cata...

    journal_title:Proceedings of the National Academy of Sciences of the United States of America

    pub_type: 杂志文章

    doi:10.1073/pnas.0602320103

    authors: Weber AL,Pizzarello S

    更新日期:2006-08-22 00:00:00

  • A theory of the chain melting phase transition of aqueous phospholipid dispersions.

    abstract::A model for the chain melting phase transition in dilute aqueous phospholipid bilayer dispersions is presented. This model includes interactions between head groups, between hydrocarbon chains, and within the chains. The head groups are modeled as hard disks which are constrained to lie on a two-dimensional surface se...

    journal_title:Proceedings of the National Academy of Sciences of the United States of America

    pub_type: 杂志文章

    doi:10.1073/pnas.72.10.3993

    authors: Jacobs RE,Hudson B,Andersen HC

    更新日期:1975-10-01 00:00:00

  • Antagonism of microRNA-126 suppresses the effector function of TH2 cells and the development of allergic airways disease.

    abstract::Allergic asthma is an inflammatory disease of the lung characterized by abnormal T helper-2 (T(H)2) lymphocyte responses to inhaled antigens. The molecular mechanisms leading to the generation of T(H)2 responses remain unclear, although toll-like receptors (TLRs) present on innate immune cells play a pivotal role in s...

    journal_title:Proceedings of the National Academy of Sciences of the United States of America

    pub_type: 杂志文章

    doi:10.1073/pnas.0905063106

    authors: Mattes J,Collison A,Plank M,Phipps S,Foster PS

    更新日期:2009-11-03 00:00:00

  • Memory T cells have gene expression patterns intermediate between naive and effector.

    abstract::The biological basis underlying differentiation of naive (NAI) T cells into effector (EFFE) and memory (MEM) cells is incompletely understood. Furthermore, whether NAI T cells serially differentiate into EFFE and then MEM cells (linear differentiation) or whether they concurrently differentiate into either EFFE or MEM...

    journal_title:Proceedings of the National Academy of Sciences of the United States of America

    pub_type: 杂志文章

    doi:10.1073/pnas.0501437102

    authors: Holmes S,He M,Xu T,Lee PP

    更新日期:2005-04-12 00:00:00

  • Mechanochemical model for myosin V.

    abstract::A rigorous numerical test of a hypothetical mechanism of a molecular motor should model explicitly the diffusive motion of the motor's degrees of freedom as well as the transition rates between the motor's chemical states. We present such a Brownian dynamics, mechanochemcial model of the coarse-grain structure of the ...

    journal_title:Proceedings of the National Academy of Sciences of the United States of America

    pub_type: 杂志文章

    doi:10.1073/pnas.0908192106

    authors: Craig EM,Linke H

    更新日期:2009-10-27 00:00:00

  • The ciliate Euplotes raikovi heterozygous at the mat genetic locus coreleases two individual species of mating pheromone: Genetic and biochemical evidence.

    abstract::Euplotes raikovi of the wild-type strain 13 was found to be heterozygous (mat-1/mat-2) for the genetic locus mat, which is supposed to control the mating-type specificity of freely released mating pheromones ("euplomones"), and capable of yielding the two types of corresponding homozygotes (mat-1/mat-1, mat-2/mat-2). ...

    journal_title:Proceedings of the National Academy of Sciences of the United States of America

    pub_type: 杂志文章

    doi:10.1073/pnas.83.9.2889

    authors: Luporini P,Raffioni S,Concetti A,Miceli C

    更新日期:1986-05-01 00:00:00

  • Exploring the aggregation free energy landscape of the amyloid-β protein (1-40).

    abstract::A predictive coarse-grained protein force field [associative memory, water-mediated, structure, and energy model for molecular dynamics (AWSEM)-MD] is used to study the energy landscapes and relative stabilities of amyloid-β protein (1-40) in the monomer and all of its oligomeric forms up to an octamer. We find that a...

    journal_title:Proceedings of the National Academy of Sciences of the United States of America

    pub_type: 杂志文章

    doi:10.1073/pnas.1612362113

    authors: Zheng W,Tsai MY,Chen M,Wolynes PG

    更新日期:2016-10-18 00:00:00