当前位置： SCI文献检索 > MOLECULAR PHARMACOLOGY期刊下所有文献 > Molecular interactions underlying the unusually high adenosine affinity of a novel Trypanosoma brucei nucleoside transporter.

Molecular interactions underlying the unusually high adenosine affinity of a novel Trypanosoma brucei nucleoside transporter.

Abstract：

:Trypanosoma brucei encodes a relatively high number of genes of the equilibrative nucleoside transporter (ENT) family. We report here the cloning and in-depth characterization of one T. brucei brucei ENT member, TbNT9/AT-D. This transporter was expressed in Saccharomyces cerevisiae and displayed a uniquely high affinity for adenosine (Km = 0.068 +/- 0.013 microM), as well as broader selectivity for other purine nucleosides in the low micromolar range, but was not inhibited by nucleobases or pyrimidines. This selectivity profile is consistent with the P1 transport activity observed previously in procyclic and long-slender bloodstream T. brucei, apart from the 40-fold higher affinity for adenosine than for inosine. We found that, like the previously investigated P1 activity of long/slender bloodstream trypanosomes, the 3'-hydroxy, 5'-hydroxy, N3, and N7 functional groups contribute to transporter binding. In addition, we show that the 6-position amine group of adenosine, but not the inosine 6-keto group, makes a major contribution to binding (DeltaG0 = 12 kJ/mol), explaining the different Km values of the purine nucleosides. We further found that P1 activity in procyclic and long-slender trypanosomes is pharmacologically distinct, and we identified the main gene encoding this activity in procyclic cells as NT10/AT-B. The presence of multiple P1-type nucleoside transport activities in T. brucei brucei facilitates the development of nucleoside-based treatments for African trypanosomiasis and would delay the onset of uptake-related drug resistance to such therapy. We show that both TbNT9/AT-D and NT10/AT-B transport a range of potentially therapeutic nucleoside analogs.

journal_name

Mol Pharmacol

journal_title

Molecular pharmacology

authors

Al-Salabi MI,Wallace LJ,Lüscher A,Mäser P,Candlish D,Rodenko B,Gould MK,Jabeen I,Ajith SN,de Koning HP

doi

10.1124/mol.106.031559

subject

Has Abstract

pub_date

2007-03-01 00:00:00

pages

921-9

issue

3

eissn

0026-895X

issn

1521-0111

pii

mol.106.031559

journal_volume

71

pub_type

杂志文章

相关文献

MOLECULAR PHARMACOLOGY文献大全
  • Hormonal regulation of hepatic organic anion transporting polypeptides.

    abstract：:Organic anion transporting polypeptides (Oatp) mediate the transport of a wide variety of amphipathic organic substrates. Rat Oatp1b2 and human OATP1B3 are members of a liver-specific subfamily of Oatps/OATPs. We investigated whether prolactin (PRL) and growth hormone (GH) regulated Oatp1b2 and OATP1B3 gene expression...

    journal_title：Molecular pharmacology

    pub_type： 杂志文章

    doi：10.1124/mol.104.010371

    authors： Wood M,Ananthanarayanan M,Jones B,Wooton-Kee R,Hoffman T,Suchy FJ,Vore M

    更新日期：2005-07-01 00:00:00

  • Stereospecific activation of cardiac ATP-sensitive K(+) channels by epoxyeicosatrienoic acids: a structural determinant study.

    abstract：:The heart is richly endowed with K(ATP) channels, which function as biological sensors, regulating membrane potentials and electrical excitability in response to metabolic alterations. We recently reported that the cytochrome P450 metabolites of arachidonic acid, epoxyeicosatrienoic acids (EETs), potently activate car...

    journal_title：Molecular pharmacology

    pub_type： 杂志文章

    doi：10.1124/mol.62.5.1076

    authors： Lu T,VanRollins M,Lee HC

    更新日期：2002-11-01 00:00:00

  • Cysteine Scanning Mutagenesis of TM4b-4c Loop of Glutamate Transporter EAAT1 Reveals Three Conformationally Sensitive Residues.

    abstract：:Glutamatergic synaptic transmitters are cleared from the synaptic cleft through excitatory amino acid transporters (EAATs) that are responsible for recycling glutamate and transporting it into neurons and glial cells. To probe the structural role of the TM4b-4c loop of EAAT1 (Rattus norvegicus), each of the 57 amino a...

    journal_title：Molecular pharmacology

    pub_type： 杂志文章

    doi：10.1124/mol.117.111245

    authors： Zhang W,Zhang X,Qu S

    更新日期：2018-07-01 00:00:00

  • Dual targeting of the androgen receptor and hypoxia-inducible factor 1α pathways synergistically inhibits castration-resistant prostate cancer cells.

    abstract：:Enzalutamide is a potent second-generation androgen receptor (AR) antagonist with activity in metastatic castrate-resistant prostate cancer (CRPC). Although enzalutamide is initially effective, disease progression inevitably ensues with the emergence of resistance. Intratumoral hypoxia is also associated with CRPC pro...

    journal_title：Molecular pharmacology

    pub_type： 杂志文章

    doi：10.1124/mol.114.097477

    authors： Fernandez EV,Reece KM,Ley AM,Troutman SM,Sissung TM,Price DK,Chau CH,Figg WD

    更新日期：2015-06-01 00:00:00

  • Down-regulation of inducible nitric-oxide synthase (NOS-2) during parasite-induced gut inflammation: a path to identify a selective NOS-2 inhibitor.

    abstract：:Nitric oxide (NO) possesses potent anti-inflammatory properties; however, an over-production of NO will promote inflammation and induce cell and tissue dysfunction. Thus, the ability to precisely regulate NO production could prove beneficial in controlling damage. In this study, advantage was taken of the well charact...

    journal_title：Molecular pharmacology

    pub_type： 杂志文章

    doi：10.1124/mol.59.4.939

    authors： Bian K,Harari Y,Zhong M,Lai M,Castro G,Weisbrodt N,Murad F

    更新日期：2001-04-01 00:00:00

  • Dolastatin 11, a marine depsipeptide, arrests cells at cytokinesis and induces hyperpolymerization of purified actin.

    abstract：:The successful synthesis of dolastatin 11, a depsipeptide originally isolated from the mollusk Dolabella auricularia, permitted us to study its effects on cells. The compound arrested cells at cytokinesis by causing a rapid and massive rearrangement of the cellular actin filament network. In a dose-and time-dependent ...

    journal_title：Molecular pharmacology

    pub_type： 杂志文章

    doi：10.1124/mol.59.3.462

    authors： Bai R,Verdier-Pinard P,Gangwar S,Stessman CC,McClure KJ,Sausville EA,Pettit GR,Bates RB,Hamel E

    更新日期：2001-03-01 00:00:00

  • Functional selectivity of D2 receptor ligands in a Chinese hamster ovary hD2L cell line: evidence for induction of ligand-specific receptor states.

    abstract：:There are now several examples of single G protein-coupled receptors to which binding of specific agonists causes differential effects on the associated signaling pathways. The dopamine D(2) receptor is of special importance because the selective activation of functional pathways has been shown both in vitro and in si...

    journal_title：Molecular pharmacology

    pub_type： 杂志文章

    doi：10.1124/mol.66.1.97

    authors： Gay EA,Urban JD,Nichols DE,Oxford GS,Mailman RB

    更新日期：2004-07-01 00:00:00

  • Reduction of calcineurin activity in brain by antisense oligonucleotides leads to persistent phosphorylation of tau protein at Thr181 and Thr231.

    abstract：:Phosphorylation of tau protein promotes stability of the axonal cytoskeleton; aberrant tau phosphorylation is implicated in the biogenesis of paired helical filaments (PHF) seen in Alzheimer's disease. Protein kinases and phosphatases that modulate tau phosphorylation have been identified using in vitro techniques; ho...

    journal_title：Molecular pharmacology

    pub_type： 杂志文章

    doi：

    authors： Garver TD,Kincaid RL,Conn RA,Billingsley ML

    更新日期：1999-04-01 00:00:00

  • Endogenous regulators of G protein signaling differentially modulate full and partial mu-opioid agonists at adenylyl cyclase as predicted by a collision coupling model.

    abstract：:Regulator of G protein signaling (RGS) proteins accelerate the endogenous GTPase activity of Galpha(i/o) proteins to increase the rate of deactivation of active Galpha-GTP and Gbetagamma signaling molecules. Previous studies have suggested that RGS proteins are more effective on less efficiently coupled systems such a...

    journal_title：Molecular pharmacology

    pub_type： 杂志文章

    doi：10.1124/mol.107.043547

    authors： Clark MJ,Linderman JJ,Traynor JR

    更新日期：2008-05-01 00:00:00

  • Amphetamines take two to tango: an oligomer-based counter-transport model of neurotransmitter transport explores the amphetamine action.

    abstract：:Amphetamine congeners [e.g., 3,4-methylenedioxymetamphetamine (MDMA), or "ecstasy"] are substrates for monoamine transporters (i.e., the transporters for serotonin, norepinephrine, and dopamine); however, their in vivo-action relies on their ability to promote monoamine efflux. The mechanistic basis for this counter t...

    journal_title：Molecular pharmacology

    pub_type： 杂志文章

    doi：10.1124/mol.67.1.

    authors： Seidel S,Singer EA,Just H,Farhan H,Scholze P,Kudlacek O,Holy M,Koppatz K,Krivanek P,Freissmuth M,Sitte HH

    更新日期：2005-01-01 00:00:00

  • Detection, quantitation, and verification of allosteric interactions of agents with labeled and unlabeled ligands at G protein-coupled receptors: interactions of strychnine and acetylcholine at muscarinic receptors.

    abstract：:Novel methods of detecting and quantitating cooperative interactions between an agent and both a tritiated (muscarinic) antagonist and the endogenous agonist (acetylcholine), acting at a common (muscarinic) receptor, have been devised. In a semiquantitative protocol, binding data are transformed into affinity ratios (...

    journal_title：Molecular pharmacology

    pub_type： 杂志文章

    doi：

    authors： Lazareno S,Birdsall NJ

    更新日期：1995-08-01 00:00:00

  • Topoisomerase II alpha promoter trans-activation early in monocytic differentiation of HL-60 human leukemia cells.

    abstract：:The cytotoxic efficacy of antitumor drugs targeted at DNA topoisomerase II (topo II) in many cases varies in direct proportion to cellular topo II content. To investigate the transcriptional control of the predominant alpha form of topo II, the 5' flanking region of the human topo II alpha gene (positions -562 to +90)...

    journal_title：Molecular pharmacology

    pub_type： 杂志文章

    doi：

    authors： Fraser DJ,Brandt TL,Kroll DJ

    更新日期：1995-04-01 00:00:00

  • Binding of [3H]Ro 11-2465. Possible identification of a subclass of [3H]imipramine binding sites.

    abstract：:Ro 11-2465 is a cyanide derivative of imipramine. In cerebral cortex homogenates, [3H] Ro 11-2465 displays a binding profile similar to that of [3H]imipramine. Agents compete with binding of [3H]Ro 11-2465 in an order of potency similar to their ability to block serotonin uptake, and raphe lesions greatly decrease the...

    journal_title：Molecular pharmacology

    pub_type： 杂志文章

    doi：

    authors： Dumbrille-Ross A,Tang SW

    更新日期：1983-05-01 00:00:00

  • Open channel block of HERG K(+) channels by vesnarinone.

    abstract：:Vesnarinone, a cardiotonic agent, blocks I(Kr) and, unlike other I(Kr) blockers, produces a frequency-dependent prolongation of action potential duration (APD). To elucidate the mechanisms, we studied the effects of vesnarinone on HERG, the cloned human I(Kr) channel, heterologously expressed in Xenopus laevis oocytes...

    journal_title：Molecular pharmacology

    pub_type： 杂志文章

    doi：10.1124/mol.60.2.244

    authors： Kamiya K,Mitcheson JS,Yasui K,Kodama I,Sanguinetti MC

    更新日期：2001-08-01 00:00:00

  • Clonidine-displacing substance from bovine brain binds to imidazoline receptors and releases catecholamines in adrenal chromaffin cells.

    abstract：:Identification of nonadrenergic binding sites for clonidine and related imidazolines in brain and peripheral tissues and partial purification of an endogenous ligand for these sites have led to the postulation of a novel transmitter/receptor system. The receptors seem to be present in adrenal medulla and to regulate c...

    journal_title：Molecular pharmacology

    pub_type： 杂志文章

    doi：

    authors： Regunathan S,Meeley MP,Reis DJ

    更新日期：1991-12-01 00:00:00

  • Myristyl trimethyl ammonium bromide and octadecyl trimethyl ammonium bromide are surface-active small molecule dynamin inhibitors that block endocytosis mediated by dynamin I or dynamin II.

    abstract：:Dynamin is a GTPase enzyme involved in membrane constriction and fission during endocytosis. Phospholipid binding via its pleckstrin homology domain maximally stimulates dynamin activity. We developed a series of surface-active small-molecule inhibitors, such as myristyl trimethyl ammonium bromide (MiTMAB) and octadec...

    journal_title：Molecular pharmacology

    pub_type： 杂志文章

    doi：10.1124/mol.107.034207

    authors： Quan A,McGeachie AB,Keating DJ,van Dam EM,Rusak J,Chau N,Malladi CS,Chen C,McCluskey A,Cousin MA,Robinson PJ

    更新日期：2007-12-01 00:00:00

  • Molecular cloning of human 5-hydroxytryptamine3 receptor: heterogeneity in distribution and function among species.

    abstract：:The 5-hydroxytryptamine3 receptor 5-HT3R has been implicated in gut and cardiac motility and in behavioral disorders. Characteristics of 5-HT3Rs appear to be heterogeneous among species, but human 5-HT3R cDNA has not been identified. We isolated a cDNA encoding 5-HT3R from human hippocampus. The mouse 5-HT3R gene has ...

    journal_title：Molecular pharmacology

    pub_type： 杂志文章

    doi：

    authors： Miyake A,Mochizuki S,Takemoto Y,Akuzawa S

    更新日期：1995-09-01 00:00:00

  • GPR139, an Orphan Receptor Highly Enriched in the Habenula and Septum, Is Activated by the Essential Amino Acids L-Tryptophan and L-Phenylalanine.

    abstract：:GPR139 is an orphan G-protein-coupled receptor expressed in the central nervous system. To identify its physiologic ligand, we measured GPR139 receptor activity from recombinant cells after treatment with amino acids, orphan ligands, serum, and tissue extracts. GPR139 activity was measured using guanosine 5'-O-(3-[(35...

    journal_title：Molecular pharmacology

    pub_type： 杂志文章

    doi：10.1124/mol.115.100412

    authors： Liu C,Bonaventure P,Lee G,Nepomuceno D,Kuei C,Wu J,Li Q,Joseph V,Sutton SW,Eckert W,Yao X,Yieh L,Dvorak C,Carruthers N,Coate H,Yun S,Dugovic C,Harrington A,Lovenberg TW

    更新日期：2015-11-01 00:00:00

  • Diphosphoinositol polyphosphates: metabolic messengers?

    abstract：:The diphosphoinositol polyphosphates ("inositol pyrophosphates") are a specialized subgroup of the inositol phosphate signaling family. This review proposes that many of the current data concerning the metabolic turnover and biological effects of the diphosphoinositol polyphosphates are linked by a common theme: these...

    journal_title：Molecular pharmacology

    pub_type： 杂志文章,评审

    doi：10.1124/mol.109.055897

    authors： Shears SB

    更新日期：2009-08-01 00:00:00

  • Characterization of a specific binding protein for 2,3,7,8-tetrachlorodibenzo-p-dioxin in human thymic epithelial cells.

    abstract：:Specific toxic and biochemical responses elicited by 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) in human thymic epithelial (TE) cells in culture are mediated by the TCDD receptor protein. Characterization of the physicochemical properties of the TCDD receptor in cytosol fractions from cultured human TE cells indicates...

    journal_title：Molecular pharmacology

    pub_type： 杂志文章

    doi：

    authors： Cook JC,Greenlee WF

    更新日期：1989-05-01 00:00:00

  • Partial agonist clonidine mediates alpha(2)-AR subtypes specific regulation of cAMP accumulation in adenylyl cyclase II transfected DDT1-MF2 cells.

    abstract：:alpha2-Adrenergic receptor (alpha(2)-AR) activation in the pregnant rat myometrium at midterm potentiates beta(2)-AR stimulation of adenylyl cyclase (AC) via Gbetagamma regulation of the type II isoform of adenylyl cyclase. However, at term, alpha(2)-AR activation inhibits beta(2)-AR stimulation of AC. This phenomenon...

    journal_title：Molecular pharmacology

    pub_type： 杂志文章

    doi：10.1124/mol.59.2.331

    authors： Limon-Boulez I,Bouet-Alard R,Gettys TW,Lanier SM,Maltier JP,Legrand C

    更新日期：2001-02-01 00:00:00

  • Organotin compounds promote adipocyte differentiation as agonists of the peroxisome proliferator-activated receptor gamma/retinoid X receptor pathway.

    abstract：:Nuclear receptors play important roles in the maintenance of the endocrine system, regulation of organ differentiation, and fetal development. Endocrine disruptors exert their adverse effects by disrupting the endocrine system via various mechanisms. To assess the effects of endocrine disruptors on nuclear receptors, ...

    journal_title：Molecular pharmacology

    pub_type： 杂志文章

    doi：10.1124/mol.104.008409

    authors： Kanayama T,Kobayashi N,Mamiya S,Nakanishi T,Nishikawa J

    更新日期：2005-03-01 00:00:00

  • The class III antiarrhythmic drug amiodarone directly activates pertussis toxin-sensitive G proteins.

    abstract：:The class III antiarrhythmic drugs amiodarone and bretylium tosylate are cationic/amphiphilic, and various substances with these physico-chemical properties are known to directly activate heterotrimeric regulatory G proteins. We asked the question of whether class III antiarrhythmic drugs are also direct G protein act...

    journal_title：Molecular pharmacology

    pub_type： 杂志文章

    doi：

    authors： Hagelüken A,Nürnberg B,Harhammer R,Grünbaum L,Schunack W,Seifert R

    更新日期：1995-02-01 00:00:00

  • Rat brain cannabinoid receptor modulates N-type Ca2+ channels in a neuronal expression system.

    abstract：:Modulation of neuronal ion channels by the cloned rat brain CB1 cannabinoid receptor was investigated with the use of a heterologous neuronal expression system. Transient expression of the rat brain CB1 cannabinoid receptor was accomplished through microinjection of in vitro transcribed cRNA into the cytoplasm of enzy...

    journal_title：Molecular pharmacology

    pub_type： 杂志文章

    doi：

    authors： Pan X,Ikeda SR,Lewis DL

    更新日期：1996-04-01 00:00:00

  • Hepatocyte nuclear factor 3 is a major determinant of CYP2C6 promoter activity in hepatoma cells.

    abstract：:Cytochrome P450 2C6 (CYP2C6) is a developmentally regulated, constitutively expressed form of rat liver microsomal cytochrome P450 that in the liver of adult male rats is induced to a limited extent by phenobarbital. The gene is not expressed at detectable levels in the lung, kidney, or brain. It is expressed and indu...

    journal_title：Molecular pharmacology

    pub_type： 杂志文章

    doi：

    authors： Shaw PM,Weiss MC,Adesnik M

    更新日期：1994-07-01 00:00:00

  • Alpha 2-adrenoceptor stimulation affects total glucose utilization in isolated islets of Langerhans.

    abstract：:Glucose utilization in isolated islets of Langerhans of the rat was determined by measuring the conversion of [5-3H]glucose (10 mM) to 3H2O. The alpha 2-adrenoceptor agonists clonidine, epinephrine, and norepinephrine in the presence of the alpha 1-adrenoceptor antagonist prazosin and the beta-adrenoceptor antagonist ...

    journal_title：Molecular pharmacology

    pub_type： 杂志文章

    doi：

    authors： Laychock SG

    更新日期：1987-08-01 00:00:00

  • Copper transporters and the cellular pharmacology of the platinum-containing cancer drugs.

    abstract：:Multiple lines of evidence indicate that the platinum-containing cancer drugs enter cells, are distributed to various subcellular compartments, and are exported from cells via transporters that evolved to manage copper homeostasis. The cytotoxicity of the platinum drugs is directly related to how much drug enters the ...

    journal_title：Molecular pharmacology

    pub_type： 杂志文章,评审

    doi：10.1124/mol.109.063172

    authors： Howell SB,Safaei R,Larson CA,Sailor MJ

    更新日期：2010-06-01 00:00:00

  • Steroid interaction with a single potentiating site is sufficient to modulate GABA-A receptor function.

    abstract：:Neuroactive steroids are efficacious potentiators of GABA-A receptors. Recent work has identified a site in the alpha1 subunit of the GABA-A receptor, that is essential for potentiation by steroids. However, each receptor contains two copies of the alpha1 subunit. We generated concatemers of subunits so that the alpha...

    journal_title：Molecular pharmacology

    pub_type： 杂志文章

    doi：10.1124/mol.108.053629

    authors： Bracamontes JR,Steinbach JH

    更新日期：2009-04-01 00:00:00

  • Ca(2+) requirement for high-affinity gamma-aminobutyric acid (GABA) binding at GABA(B) receptors: involvement of serine 269 of the GABA(B)R1 subunit.

    abstract：:The gamma-aminobutyric acid (GABA) receptor type B (GABA(B)R) is constituted of at least two homologous proteins, GABA(B)R1 and GABA(B)R2. These proteins share sequence and structural similarity with metabotropic glutamate and Ca(2+)-sensing receptors, both of which are sensitive to Ca(2+). Using rat brain membranes, ...

    journal_title：Molecular pharmacology

    pub_type： 杂志文章

    doi：10.1124/mol.57.3.419

    authors： Galvez T,Urwyler S,Prézeau L,Mosbacher J,Joly C,Malitschek B,Heid J,Brabet I,Froestl W,Bettler B,Kaupmann K,Pin JP

    更新日期：2000-03-01 00:00:00

  • Investigation of the molecular mechanism of the α7 nicotinic acetylcholine receptor positive allosteric modulator PNU-120596 provides evidence for two distinct desensitized states.

    abstract：:Although α7 nicotinic acetylcholine receptors are considered potentially important therapeutic targets, the development of selective agonists has been stymied by the α7 receptor's intrinsically low probability of opening (P(open)) and the concern that an agonist-based therapeutic approach would disrupt endogenous chol...

    journal_title：Molecular pharmacology

    pub_type： 杂志文章

    doi：10.1124/mol.111.074302

    authors： Williams DK,Wang J,Papke RL

    更新日期：2011-12-01 00:00:00