Picrate and niflumate block anion modulation of radioligand binding to the gamma-aminobutyric acid/benzodiazepine receptor complex.

Abstract:

:The organic anions picrate (2,4,6-trinitrophenol) and niflumate (2-[[3-(trifluoromethyl)phenyl]-amino]-3-pyridinecarboxylate) were examined for their effects on radioligand binding to the gamma-aminobutyric acid (GABA)/benzodiazepine receptor complex. Neither organic anion produced the enhancement of [35S] t-butylbicyclophosphorothionate (TBPS) binding characteristic of anions (such as Cl- and Br-) known to permeate GABA-gated chloride channels. However, both picrate and niflumate potently (IC50 values between 66 and 531 and 30 and 155 microM, respectively) inhibited the effect of 100-200 mM concentrations of anions (I-, Br-, Cl-, SCN-, and F-) to increase the binding of [35S]TBPS to GABA-gated chloride channels. This inhibition resulted from a decrease in both the maximum number of binding sites and the apparent affinity (increased Kd) of [35S]TBPS. Niflumate was consistently more potent than picrate, but both organic anions exhibited the same sequence of relative potencies against smaller anions (I- greater than Br- greater than Cl- greater than SCN- greater than F-). This sequence was similar to that described for the relative permeabilities of these anions through GABA-gated chloride channels. Niflumate and picrate were potent inhibitors of Cl-, but not GABA-modulated radioligand binding to benzodiazepine receptors. These findings suggest that picrate and niflumate bind with high affinity at or near an anion binding site that may regulate the movement of anions through GABA-gated chloride channels and radioligand binding at this "supramolecular complex."

journal_name

Mol Pharmacol

journal_title

Molecular pharmacology

authors

Evoniuk G,Skolnick P

subject

Has Abstract

pub_date

1988-12-01 00:00:00

pages

837-42

issue

6

eissn

0026-895X

issn

1521-0111

journal_volume

34

pub_type

杂志文章
  • Identification of a glucocorticoid response element in the rat beta2-adrenergic receptor gene.

    abstract::Regulation of beta2-adrenergic receptor (beta2AR) levels by glucocorticoids is a physiologically important mechanism for altering beta2AR responsiveness. Glucocorticoids increase beta2AR density by increasing the rate of beta2AR gene transcription, but the cis-elements involved have not been well characterized. We now...

    journal_title:Molecular pharmacology

    pub_type: 杂志文章

    doi:10.1124/mol.54.6.1016

    authors: Cornett LE,Hiller FC,Jacobi SE,Cao W,McGraw DW

    更新日期:1998-12-01 00:00:00

  • Involvement of phenyl radicals in iodonium inhibition of flavoenzymes.

    abstract::Iodonium inhibition of the flavoenzymes neutrophil NADPH oxidase and cytochrome P450 reductase has been suggested to require reductive metabolism of the inhibitor to a phenyl radical. Inhibition would ultimately result from covalent attachment of phenyl radicals to either the flavin cofactor or adjacent amino acid sid...

    journal_title:Molecular pharmacology

    pub_type: 杂志文章

    doi:

    authors: O'Donnell VB,Smith GC,Jones OT

    更新日期:1994-10-01 00:00:00

  • Selectivity for binding of peptide analogs to vascular receptors for vasoactive intestinal peptide.

    abstract::The structure-activity relationships for vasoactive intestinal peptide (VIP) receptor binding were studied using N-terminally modified VIP analogs. VIP fragments, and VIP receptor antagonists. Tissue sources included bovine coronary artery, rat mesenteric artery, rat pituitary, rat brain synaptosomes, and rat liver. E...

    journal_title:Molecular pharmacology

    pub_type: 杂志文章

    doi:

    authors: Rorstad OP,Wanke I,Coy DH,Fournier A,Huang M

    更新日期:1990-06-01 00:00:00

  • Paclitaxel-induced immune suppression is associated with NF-kappaB activation via conventional PKC isotypes in lipopolysaccharide-stimulated 70Z/3 pre-B lymphocyte tumor cells.

    abstract::Paclitaxel, a potent antitumor agent, has been shown to be lipopolysaccharide (LPS) mimetic in mice, stimulating signaling pathways and gene expression indistinguishably from LPS. In the present study, we showed the intracellular signaling pathway of paclitaxel-induced nuclear factor-kappaB (NF-kappaB) activation and ...

    journal_title:Molecular pharmacology

    pub_type: 杂志文章

    doi:10.1124/mol.59.2.248

    authors: Lee M,Jeon YJ

    更新日期:2001-02-01 00:00:00

  • Characterization of bicuculline/baclofen-insensitive (rho-like) gamma-aminobutyric acid receptors expressed in Xenopus oocytes. II. Pharmacology of gamma-aminobutyric acidA and gamma-aminobutyric acidB receptor agonists and antagonists.

    abstract::Poly(A)+ RNA from mammalian retina expresses bicuculline/baclofen-insensitive gamma-aminobutyric acid (GABA) receptors in Xenopus oocytes with properties similar to those of homooligomeric GABA rho 1 receptors. The pharmacological profile of these rho-like receptors was extended by measuring sensitivities to various G...

    journal_title:Molecular pharmacology

    pub_type: 杂志文章

    doi:

    authors: Woodward RM,Polenzani L,Miledi R

    更新日期:1993-04-01 00:00:00

  • In vivo involvement of heparan sulfate proteoglycan in the bioavailability, internalization, and catabolism of exogenous basic fibroblast growth factor.

    abstract::The in vivo bioavailability of exogenous fibroblast growth factor 2 (FGF2) was studied after i.v. injection of uniformly 14C-labeled FGF2 into young rats. 14C-FGF2 was rapidly accumulated in almost all solid organs within 5 min. After 30 min, more than 65% of FGF2 was retained in liver, 4.5% in kidneys, 1.2% in spleen...

    journal_title:Molecular pharmacology

    pub_type: 杂志文章

    doi:10.1124/mol.55.1.74

    authors: Colin S,Jeanny JC,Mascarelli F,Vienet R,Al-Mahmood S,Courtois Y,Labarre J

    更新日期:1999-01-01 00:00:00

  • Evidence that cytochrome b5 and cytochrome b5 reductase can act as sole electron donors to the hepatic cytochrome P450 system.

    abstract::We previously described the development of genetic models to study the in vivo functions of the hepatic cytochrome P450 (P450) system, through the hepatic deletion of either cytochrome P450 oxidoreductase [POR; HRN (hepatic reductase null) line] or cytochrome b(5) [HBN (hepatic cytochrome b(5) null) line]. However, HR...

    journal_title:Molecular pharmacology

    pub_type: 杂志文章

    doi:10.1124/mol.112.084616

    authors: Henderson CJ,McLaughlin LA,Wolf CR

    更新日期:2013-06-01 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

  • Molecular basis for the selective interaction of synthetic agonists with the human histamine H1-receptor compared with the guinea pig H1-receptor.

    abstract::Previous studies revealed that phenylhistamines and histaprodifens possess higher potency and affinity at guinea pig histamine H(1)-receptor (gpH(1)R) than at human histamine H(1)-receptor (hH(1)R). However, we recently identified an imidazolylpropylguanidine [N(1)-(3-cyclohexylbutanoyl)-N(2)-[3-(1H-imidazol-4-yl)-pro...

    journal_title:Molecular pharmacology

    pub_type: 杂志文章

    doi:10.1124/mol.108.053009

    authors: Strasser A,Wittmann HJ,Kunze M,Elz S,Seifert R

    更新日期:2009-03-01 00:00:00

  • Modeling the effects of β1-adrenergic receptor blockers and polymorphisms on cardiac myocyte Ca2+ handling.

    abstract::β-Adrenergic receptor blockers (β-blockers) are commonly used to treat heart failure, but the biologic mechanisms governing their efficacy are still poorly understood. The complexity of β-adrenergic signaling coupled with the influence of receptor polymorphisms makes it difficult to intuit the effect of β-blockers on ...

    journal_title:Molecular pharmacology

    pub_type: 杂志文章

    doi:10.1124/mol.113.090951

    authors: Amanfu RK,Saucerman JJ

    更新日期:2014-08-01 00:00:00

  • N-methyl-D-aspartate receptors activate transcription of c-fos and NGFI-A by distinct phospholipase A2-requiring intracellular signaling pathways.

    abstract::Activation of N-methyl-D-aspartate (NMDA) receptors is required for induction of some lasting changes in nervous system structure and function. The cellular mechanisms involved in transducing receptor stimulation into long-lasting changes in cellular activity are unknown. Immediate-early genes (IEGs) have been implica...

    journal_title:Molecular pharmacology

    pub_type: 杂志文章

    doi:

    authors: Lerea LS,Carlson NG,McNamara JO

    更新日期:1995-06-01 00:00:00

  • Essential role of C-Rel in nitric-oxide synthase-2 transcriptional activation: time-dependent control by salicylate.

    abstract::To determine the role of C-Rel in nitric-oxide synthase-2 (NOS-2) transcriptional activation, we evaluated the effect of lipopolysaccharide and interferon-gamma (LPS/IFNgamma) on C-Rel DNA binding in RAW 264.7. LPS/IFNgamma-stimulated C-Rel binding peaked at 4 to 8 h and declined at 24 h. Transfection of cells with a ...

    journal_title:Molecular pharmacology

    pub_type: 杂志文章

    doi:10.1124/mol.106.026054

    authors: Cieslik KA,Deng WG,Wu KK

    更新日期:2006-12-01 00:00:00

  • The Pharmacology and Function of Receptors for Short-Chain Fatty Acids.

    abstract::Despite some blockbuster G protein-coupled receptor (GPCR) drugs, only a small fraction (∼ 15%) of the more than 390 nonodorant GPCRs have been successfully targeted by the pharmaceutical industry. One way that this issue might be addressed is via translation of recent deorphanization programs that have opened the pro...

    journal_title:Molecular pharmacology

    pub_type: 杂志文章,评审

    doi:10.1124/mol.115.102301

    authors: Bolognini D,Tobin AB,Milligan G,Moss CE

    更新日期:2016-03-01 00:00:00

  • Synergy between coproduced CC and CXC chemokines in monocyte chemotaxis through receptor-mediated events.

    abstract::CC and CXC chemokines coinduced in fibroblasts and leukocytes by cytokines and microbial agents determine the number of phagocytes infiltrating into inflamed tissues. Interleukin-8/CXCL8 and stromal cell-derived factor-1/CXCL12 significantly and dose-dependently increased the migration of monocytes, expressing the cor...

    journal_title:Molecular pharmacology

    pub_type: 杂志文章

    doi:10.1124/mol.108.045146

    authors: Gouwy M,Struyf S,Noppen S,Schutyser E,Springael JY,Parmentier M,Proost P,Van Damme J

    更新日期:2008-08-01 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

  • A Latin American Perspective on G Protein-Coupled Receptors.

    abstract::G protein-coupled receptors are sensors that interact with a large variety of elements, including photons, ions, and large proteins. Not surprisingly, these receptors participate in the numerous normal physiologic processes that we refer to as health and in its perturbations that constitute disease. It has been estima...

    journal_title:Molecular pharmacology

    pub_type:

    doi:10.1124/mol.116.106062

    authors: Pupo AS,García-Sáinz JA

    更新日期:2016-11-01 00:00:00

  • Opposite effects of histone deacetylase inhibitors on glucocorticoid and estrogen signaling in human endometrial Ishikawa cells.

    abstract::Histone deacetylase inhibitors (HDACi), which have emerged as a new class of anticancer agents, act by modulating expression of genes controlling apoptosis or cell proliferation. Here, we compared the effect of HDACi on transcriptional activation by estrogen or glucocorticoid receptors (ER and GR, respectively), two m...

    journal_title:Molecular pharmacology

    pub_type: 杂志文章

    doi:10.1124/mol.105.014514

    authors: Rocha W,Sanchez R,Deschênes J,Auger A,Hébert E,White JH,Mader S

    更新日期:2005-12-01 00:00:00

  • Photoaffinity labeling and purification of ZG-16p, a high-affinity dihydropyridine binding protein of rat pancreatic zymogen granule membranes that regulates a K(+)-selective conductance.

    abstract::In rat pancreatic zymogen granules (ZG), an ATP-sensitive K(+) conductance and a Cl(-) conductance have been characterized that are inversely regulated by an approximately 65-kDa multidrug resistance P-glycoprotein (mdr1) gene product. In search of a label for purification of this protein, we found that the dihydropyr...

    journal_title:Molecular pharmacology

    pub_type: 杂志文章

    doi:

    authors: Braun M,Thévenod F

    更新日期:2000-02-01 00:00:00

  • Gastrin-releasing peptide receptor signaling resulting in growth inhibition.

    abstract::We demonstrate that gastrin-releasing peptide (GRP) can inhibit the proliferation of human immortal nontumorigenic (184-B5) mammary epithelial cells ectopically expressing the human GRP receptor. Growth of Balb 3T3 cells ectopically expressing relatively high levels of the GRP receptor was also inhibited by GRP; howev...

    journal_title:Molecular pharmacology

    pub_type: 杂志文章

    doi:

    authors: Feldman RI,Fried S,Mann E,Wu JM,Liang M

    更新日期:1996-03-01 00:00:00

  • Targeted disruption of the multidrug and toxin extrusion 1 (mate1) gene in mice reduces renal secretion of metformin.

    abstract::Multidrug and toxin extrusion 1 (MATE1/SLC47A1) is important for excretion of organic cations in the kidney and liver, where it is located on the luminal side. Although its functional and regulatory characteristics have been clarified, its pharmacokinetic roles in vivo have yet to be elucidated. In the present study, ...

    journal_title:Molecular pharmacology

    pub_type: 杂志文章

    doi:10.1124/mol.109.056242

    authors: Tsuda M,Terada T,Mizuno T,Katsura T,Shimakura J,Inui K

    更新日期:2009-06-01 00:00:00

  • Receptor-mediated inositol phosphate formation in relation to calcium mobilization: a comparison of two cell lines.

    abstract::Previous studies indicated that activation of alpha 1-adrenergic receptors in BC3H-1 muscle cells (S. K. Ambler and P. Taylor, J. Biol. Chem. 261:5866-5871, 1986) and muscarinic receptors in 1321N1 astrocytoma cells (S. B. Masters, T. K. Harden, and J. H. Brown, Mol. Pharmacol. 27:325-332, 1985) resulted in the rapid ...

    journal_title:Molecular pharmacology

    pub_type: 杂志文章

    doi:

    authors: Ambler SK,Thompson B,Solski PA,Brown JH,Taylor P

    更新日期:1987-09-01 00:00:00

  • Evidence that gamma-secretase-mediated Notch signaling induces neuronal cell death via the nuclear factor-kappaB-Bcl-2-interacting mediator of cell death pathway in ischemic stroke.

    abstract::Notch-1 (Notch) is a cell surface receptor that regulates cell-fate decisions in the developing nervous system, and it may also have roles in synaptic plasticity in the adult brain. Binding of its ligands results in the proteolytic cleavage of Notch by the γ-secretase enzyme complex, thereby causing the release of a N...

    journal_title:Molecular pharmacology

    pub_type: 杂志文章

    doi:10.1124/mol.111.071076

    authors: Arumugam TV,Cheng YL,Choi Y,Choi YH,Yang S,Yun YK,Park JS,Yang DK,Thundyil J,Gelderblom M,Karamyan VT,Tang SC,Chan SL,Magnus T,Sobey CG,Jo DG

    更新日期:2011-07-01 00:00:00

  • Interaction of [3H]orphanin FQ and 125I-Tyr14-orphanin FQ with the orphanin FQ receptor: kinetics and modulation by cations and guanine nucleotides.

    abstract::The heptadecapeptide orphanin FQ (OFQ) has been identified as the endogenous ligand for a G protein-coupled receptor (OFQ-R), which, despite its high degree of sequence similarity to opioid receptors, fails to bind opioid ligands. We developed two radioligands for the OFQ-R: a tritiated native OFQ peptide ([3H]OFQ) an...

    journal_title:Molecular pharmacology

    pub_type: 杂志文章

    doi:10.1124/mol.51.5.816

    authors: Ardati A,Henningsen RA,Higelin J,Reinscheid RK,Civelli O,Monsma FJ Jr

    更新日期:1997-05-01 00:00:00

  • New signaling mechanism of angiotensin II in neuroblastoma neuro-2A cells: activation of soluble guanylyl cyclase via nitric oxide synthesis.

    abstract::We previously reported that angiotensin II (Ang II) increases cGMP content through a new Ang II receptor subtype that is distinct from both the AT1 and AT2 subtypes in differentiated Neuro-2A cells. In this study, the mechanism of the Ang II-stimulated cGMP increase was investigated in comparison with bradykinin- and ...

    journal_title:Molecular pharmacology

    pub_type: 杂志文章

    doi:

    authors: Chaki S,Inagami T

    更新日期:1993-04-01 00:00:00

  • Effect of ethanol on intracellular ionized calcium concentrations in synaptosomes and hepatocytes.

    abstract::The effect of ethanol on intracellular ionized calcium concentrations (Cai) was studied in synaptosomes isolated from mouse whole brain and in hepatocytes isolated from rat liver. The fluorescent calcium chelator, fura-2, was used to quantitate Cai. Incubation of synaptosomes with ethanol (350-700 mM) increased restin...

    journal_title:Molecular pharmacology

    pub_type: 杂志文章

    doi:

    authors: Daniell LC,Brass EP,Harris RA

    更新日期:1987-12-01 00:00:00

  • Efficacy as a vector: the relative prevalence and paucity of inverse agonism.

    abstract::This article describes the expected phenotypic behavior of all types of ligands in constitutively active receptor systems and, in particular, the molecular mechanisms of inverse agonism. The possible physiological relevance of inverse agonism also is discussed. Competitive antagonists with the molecular property of ne...

    journal_title:Molecular pharmacology

    pub_type: 杂志文章,评审

    doi:10.1124/mol.65.1.2

    authors: Kenakin T

    更新日期:2004-01-01 00:00:00

  • Structural Determinants for the Selectivity of the Positive KCa3.1 Gating Modulator 5-Methylnaphtho[2,1-d]oxazol-2-amine (SKA-121).

    abstract::Intermediate-conductance (KCa3.1) and small-conductance (KCa2) calcium-activated K+ channels are gated by calcium binding to calmodulin (CaM) molecules associated with the calmodulin-binding domain (CaM-BD) of these channels. The existing KCa activators, such as naphtho[1,2-d]thiazol-2-ylamine (SKA-31), 6,7-dichloro-1...

    journal_title:Molecular pharmacology

    pub_type: 杂志文章

    doi:10.1124/mol.117.109421

    authors: Brown BM,Shim H,Zhang M,Yarov-Yarovoy V,Wulff H

    更新日期:2017-10-01 00:00:00

  • Cell cycle signaling by endothelin-1 requires Src nonreceptor protein tyrosine kinase.

    abstract::Cross-talk between G protein-coupled receptors and protein tyrosine kinases is well established, but the phenotypic consequences of these signaling interactions are not completely understood. To investigate the role of Src family kinases in mitogenic signaling by G protein-coupled receptors, we used genetic and pharma...

    journal_title:Molecular pharmacology

    pub_type: 杂志文章

    doi:10.1124/mol.104.010546

    authors: Mishra R,Wang Y,Simonson MS

    更新日期:2005-06-01 00:00:00

  • A new method to study glutathione adduct formation in periportal and pericentral regions of the liver lobule by micro-reflectance spectrophotometry.

    abstract::A method was developed to measure the formation of glutathione adducts of 1-chloro-2,4-dinitrobenzene (CDNB) and 2,4-dichloro-1-nitrobenzene (DCNB) in periportal and pericentral regions of the liver lobule in the isolated perfused rat liver by surface reflectance spectrophotometry. Conjugates of DCNB and CDNB are rele...

    journal_title:Molecular pharmacology

    pub_type: 杂志文章

    doi:

    authors: Harris C,Thurman RG

    更新日期:1986-01-01 00:00:00

  • Bcl-2 down-regulation is a novel mechanism of paclitaxel resistance.

    abstract::Taxanes act by inhibiting microtubule dynamics; in this study, we have investigated mitochondria as an additional target of taxanes. We incubated isolated mitochondria in the presence of taxanes with or without stimulation of the mitochondrial respiratory state. Results showed that they rapidly induced the loss of del...

    journal_title:Molecular pharmacology

    pub_type: 杂志文章

    doi:10.1124/mol.64.1.51

    authors: Ferlini C,Raspaglio G,Mozzetti S,Distefano M,Filippetti F,Martinelli E,Ferrandina G,Gallo D,Ranelletti FO,Scambia G

    更新日期:2003-07-01 00:00:00