Use of knockout technology to resolve pharmacological problems.

Abstract:

:Knock-out (KO) mouse technology has given pharmacologists a powerful tool to study function in the absence of selective antagonists or inhibitors. Such KO technology can confirm predicted function, serendipitously reveal unrecognized function, or help define the mode of action of a drug. In this issue, Liles et al. demonstrate, employing mice unable to synthesize noradrenaline due to the KO of the dopamine-beta-hydroxylase gene, that the sympathomimetic actions of ephedrine are directly, rather than indirectly, mediated. This may end 50 years of debate about the actions of ephedrine.

journal_name

Br J Pharmacol

authors

Docherty JR

doi

10.1038/sj.bjp.0706941

subject

Has Abstract

pub_date

2007-01-01 00:00:00

pages

1-2

issue

1

eissn

0007-1188

issn

1476-5381

pii

0706941

journal_volume

150

pub_type

评论,杂志文章
  • Pharmacological profile of novel psychoactive benzofurans.

    abstract:BACKGROUND AND PURPOSE:Benzofurans are newly used psychoactive substances, but their pharmacology is unknown. The aim of the present study was to pharmacologically characterize benzofurans in vitro. EXPERIMENTAL APPROACH:We assessed the effects of the benzofurans 5-APB, 5-APDB, 6-APB, 6-APDB, 4-APB, 7-APB, 5-EAPB and ...

    journal_title:British journal of pharmacology

    pub_type: 杂志文章

    doi:10.1111/bph.13128

    authors: Rickli A,Kopf S,Hoener MC,Liechti ME

    更新日期:2015-07-01 00:00:00

  • Quantification of the characteristics of antagonists exhibiting both competitive antagonism and functional interaction.

    abstract::Null equations have been derived which, when applied to log10 concentration-tissue state curves for an agonist determined in the presence and absence of a competitive antagonist which also exhibits functional interaction, allow quantitation of the characteristics of the competitive and functional interactant effects. ...

    journal_title:British journal of pharmacology

    pub_type: 杂志文章

    doi:10.1111/j.1476-5381.1985.tb08856.x

    authors: Hughes IE,Mackay D

    更新日期:1985-05-01 00:00:00

  • Malondialdehyde inhibits cardiac contractile function in ventricular myocytes via a p38 mitogen-activated protein kinase-dependent mechanism.

    abstract::(1) Increased oxidative stress plays a significant role in the etiology of cardiovascular disease. Lipid peroxidation, initiated in the presence of hydroxy radicals resulting in the production of malondialdehyde, directly produces oxidative stress. This study was designed to examine the direct impact of malondialdehyd...

    journal_title:British journal of pharmacology

    pub_type: 杂志文章

    doi:10.1038/sj.bjp.0705384

    authors: Folden DV,Gupta A,Sharma AC,Li SY,Saari JT,Ren J

    更新日期:2003-08-01 00:00:00

  • Pharmacological actions of a new -adrenoceptor agonist, MJ-9184-1, in anaesthetized cats.

    abstract::1. The effects of (-)-isoprenaline and the new beta-adrenoceptor agonist, MJ-9184-1, on the lungs, on the cardiovascular system, and on slow contracting skeletal muscle have been compared in cats under chloralose anaesthesia.2. Both amines reduced the increases in airways resistance produced by 5-HT, depressed incompl...

    journal_title:British journal of pharmacology

    pub_type: 杂志文章

    doi:10.1111/j.1476-5381.1972.tb08134.x

    authors: Gwee MC,Nott MW,Raper C,Rodger IW

    更新日期:1972-11-01 00:00:00

  • A truncated form of CKbeta8-1 is a potent agonist for human formyl peptide-receptor-like 1 receptor.

    abstract::1. Human formyl peptide-receptor-like-1 (FPRL-1) is a promiscuous G protein-coupled receptor (GPCR), and belongs to a chemoattractant receptor family protein. This receptor has been reported to interact with various host-derived peptides and lipids involved in inflammatory responses. We described here, a novel role fo...

    journal_title:British journal of pharmacology

    pub_type: 杂志文章

    doi:10.1038/sj.bjp.0705592

    authors: Elagoz A,Henderson D,Babu PS,Salter S,Grahames C,Bowers L,Roy MO,Laplante P,Grazzini E,Ahmad S,Lembo PM

    更新日期:2004-01-01 00:00:00

  • Threonine532 phosphorylation in ClC-3 channels is required for angiotensin II-induced Cl(-) current and migration in cultured vascular smooth muscle cells.

    abstract:BACKGROUND AND PURPOSE:Angiotensin II (AngII) induces migration and growth of vascular smooth muscle cell (VSMC), which is responsible for vascular remodelling in some cardiovascular diseases. Ang II also activates a Cl(-) current, but the underlying mechanism is not clear. EXPERIMENTAL APPROACH:The A10 cell line and ...

    journal_title:British journal of pharmacology

    pub_type: 杂志文章

    doi:10.1111/bph.13385

    authors: Ma MM,Lin CX,Liu CZ,Gao M,Sun L,Tang YB,Zhou JG,Wang GL,Guan YY

    更新日期:2016-02-01 00:00:00

  • The effects of vasoactive intestinal polypeptide and of adenosine 5'-triphosphate on the isolated anococcygeus muscle of the mouse.

    abstract::1 Vasoactive intestinal polypeptide (VIP, 0.01- MicroM) produced dose-related relaxations of the mouse anococcygeus muscle. 2 Following incubation with indomethacin (2.8 microM 1 h) adenosine 5'-triphosphate (ATP, 0.5-10 mM) produced dose-related relaxations of the mouse anococcygeus. 3 Haemolysed blood reduced inhibi...

    journal_title:British journal of pharmacology

    pub_type: 杂志文章

    doi:10.1111/j.1476-5381.1982.tb09274.x

    authors: Gibson A,Tucker JF

    更新日期:1982-09-01 00:00:00

  • Altered pharmacology of native rodent spinal cord TRPV1 after phosphorylation.

    abstract:BACKGROUND AND PURPOSE:Evidence suggests that phosphorylation of TRPV1 is an important component underlying its aberrant activation in pathological pain states. To date, the detailed pharmacology of diverse TRPV1 receptor agonists and antagonists has yet to be reported for native TRPV1 under phosphorylating conditions....

    journal_title:British journal of pharmacology

    pub_type: 杂志文章

    doi:10.1111/bph.12005

    authors: Mogg AJ,Mill CE,Folly EA,Beattie RE,Blanco MJ,Beck JP,Broad LM

    更新日期:2013-02-01 00:00:00

  • The gasotransmitter hydrogen sulphide decreases Na⁺ transport across pulmonary epithelial cells.

    abstract::BACKGROUND AND PURPOSE The transepithelial absorption of Na(+) in the lungs is crucial for the maintenance of the volume and composition of epithelial lining fluid. The regulation of Na(+) transport is essential, because hypo- or hyperabsorption of Na(+) is associated with lung diseases such as pulmonary oedema or cys...

    journal_title:British journal of pharmacology

    pub_type: 杂志文章

    doi:10.1111/j.1476-5381.2012.01909.x

    authors: Althaus M,Urness KD,Clauss WG,Baines DL,Fronius M

    更新日期:2012-07-01 00:00:00

  • Inhibition of neutrophil and monocyte recruitment by endogenous and exogenous lipocortin 1.

    abstract::1. The role played by endogenous lipocortin 1 in the anti-migratory action exerted by dexamethasone (Dex) on monocyte recruitment in an in vivo model of acute inflammation was investigated by use of several neutralizing polyclonal antibodies raised against lipocortin 1 or a lipocortin 1-derived N-terminus peptide (pep...

    journal_title:British journal of pharmacology

    pub_type: 杂志文章

    doi:10.1038/sj.bjp.0701029

    authors: Getting SJ,Flower RJ,Perretti M

    更新日期:1997-03-01 00:00:00

  • 5-Hydroxytryptamine receptors that facilitate excitatory neuromuscular transmission in the guinea-pig isolated detrusor muscle.

    abstract::1. In isolated detrusor strips from the guinea-pig urinary bladder, contractile responses to electrical field stimulation were mostly mediated by neurally released acetylcholine (ACh) and adenosine 5'-triphosphate (ATP). 2. 5-Hydroxytryptamine (5-HT) produced a concentration-dependent increase in the amplitude of stim...

    journal_title:British journal of pharmacology

    pub_type: 杂志文章

    doi:10.1111/j.1476-5381.1995.tb14986.x

    authors: Messori E,Rizzi CA,Candura SM,Lucchelli A,Balestra B,Tonini M

    更新日期:1995-06-01 00:00:00

  • Pharmacology of the octopamine receptor from locust central nervous tissue (OAR3).

    abstract::1. The present study characterized highly effective agonists from different classes of compounds for the neuronal octopamine receptor (OAR3) of the migratory locust (Locusta migratoria L.). Biogenic amines and phenyliminoimidazolidines (PIIs) were employed for the study of structure-activity relationships. 2. The high...

    journal_title:British journal of pharmacology

    pub_type: 杂志文章

    doi:10.1111/j.1476-5381.1995.tb14927.x

    authors: Roeder T

    更新日期:1995-01-01 00:00:00

  • Mediterranean diet and health status: Active ingredients and pharmacological mechanisms.

    abstract::The Mediterranean diet (MedDiet) is one of the most widely described and evaluated dietary patterns in scientific literature. It is characterized by high intakes of vegetables, legumes, fruits, nuts, grains, fish, seafood, extra virgin olive oil, and a moderate intake of red wine. A large body of observational and exp...

    journal_title:British journal of pharmacology

    pub_type: 杂志文章,评审

    doi:10.1111/bph.14778

    authors: Schwingshackl L,Morze J,Hoffmann G

    更新日期:2020-03-01 00:00:00

  • Aspirin at therapeutic concentrations does not affect 5-hydroxytryptamine uptake by platelets.

    abstract::Aspirin at therapeutic concentrations does not inhibit the uptake of 5-hydroxytryptamine (5-HT) by blood platelets nor induce release of 5-HT from platelets, although platelet aggregation responses to collagen and arachidonic acid (which are dependent on platelet prostaglandin synthesis) are abolished. This does not s...

    journal_title:British journal of pharmacology

    pub_type: 杂志文章

    doi:10.1111/j.1476-5381.1977.tb07735.x

    authors: Drummond AH,MacIntyre DE,Olverman HJ

    更新日期:1977-04-01 00:00:00

  • Spinal 5-HT-receptors and tonic modulation of transmission through a withdrawal reflex pathway in the decerebrated rabbit.

    abstract::1. In decerebrated, non-spinalized rabbits, intrathecal administration of either of the selective 5-HT1A-receptor antagonists (S)WAY-100135 or WAY-100635 resulted in dose-dependent enhancement of the reflex responses of gastrocnemius motoneurones evoked by electrical stimulation of all myelinated afferents of the sura...

    journal_title:British journal of pharmacology

    pub_type: 杂志文章

    doi:10.1111/j.1476-5381.1996.tb16019.x

    authors: Clarke RW,Harris J,Houghton AK

    更新日期:1996-11-01 00:00:00

  • Tumour endoproteases: the cutting edge of cancer drug delivery?

    abstract::Despite progression in anticancer drug development and improvements in the clinical utilization of therapies, current treatment regimes are still dependent upon the use of systemic antiproliferative cytotoxic agents. Although these agents are unquestionably potent, their efficacy is limited by toxicity towards 'normal...

    journal_title:British journal of pharmacology

    pub_type: 杂志文章,评审

    doi:10.1038/sj.bjp.0707657

    authors: Atkinson JM,Siller CS,Gill JH

    更新日期:2008-04-01 00:00:00

  • Some pharmacological and biochemical interactions of the enantiomers of adenylyl 5'-(beta, gamma-methylene)-diphosphonate with the guinea-pig urinary bladder.

    abstract::Adenosine 5'-triphosphate (ATP) and adenylyl 5'-(beta, gamma-methylene)-diphosphonate (AMP-PCP) both contracted the guinea-pig urinary bladder, but the response to AMP-PCP was much greater. We synthesized the enantiomer of AMP-PCP, L-adenylyl 5'-(beta, gamma-methylene)-diphosphonate (L-AMP-PCP), and tested it on the g...

    journal_title:British journal of pharmacology

    pub_type: 杂志文章

    doi:10.1111/j.1476-5381.1984.tb16453.x

    authors: Cusack NJ,Hourani SM

    更新日期:1984-05-01 00:00:00

  • Methyl p-hydroxybenzoate causes pain sensation through activation of TRPA1 channels.

    abstract:BACKGROUND AND PURPOSE:Parabens are commonly added in pharmaceutical, cosmetic and food products because of their wide antibacterial properties, low toxicity, inertness and chemical stability, although the molecular mechanism of their antibacterial effect is not fully understood. Some agonists of the transient receptor...

    journal_title:British journal of pharmacology

    pub_type: 杂志文章

    doi:10.1038/sj.bjp.0707219

    authors: Fujita F,Moriyama T,Higashi T,Shima A,Tominaga M

    更新日期:2007-05-01 00:00:00

  • Circadian rhythm of dihydrouracil/uracil ratios in biological fluids: a potential biomarker for dihydropyrimidine dehydrogenase levels.

    abstract::1. In many cancer patients, 5-fluorouracil (5-FUra) treatment is toxic and even causes death. Nevertheless, all patients are subjected to a standard therapy regimen because there is no reliable way to identify beforehand those patients who are predisposed to 5-FUra-induced toxicity. In this study, we identified the di...

    journal_title:British journal of pharmacology

    pub_type: 临床试验,杂志文章

    doi:10.1038/sj.bjp.0705651

    authors: Jiang H,Lu J,Ji J

    更新日期:2004-02-01 00:00:00

  • Mast cell involvement in the adenosine mediated airway hyper-reactivity in a murine model of ovalbumin-induced lung inflammation.

    abstract::Airway hyper-reactivity to inhaled adenosine, mediated via mast cell activation, is a cardinal feature of asthma. Animal models have been developed in several species to mimic this phenomenon, but only in the rat has a mast cell involvement been clearly defined. In this study, a model of ovalbumin-induced adenosine hy...

    journal_title:British journal of pharmacology

    pub_type: 杂志文章

    doi:10.1038/sj.bjp.0706271

    authors: Wyss D,Bonneau O,Trifilieff A

    更新日期:2005-08-01 00:00:00

  • Activation of type 5 metabotropic glutamate receptors enhances NMDA responses in mice cortical wedges.

    abstract::1. We measured the effects of agonists and antagonists of metabotropic glutamate (mGlu) receptors (types 1 and 5) on NMDA-induced depolarization of mouse cortical wedges in order to characterize the mGlu receptor type responsible for modulating NMDA responses. We also characterized a number of mGlu receptor agents by ...

    journal_title:British journal of pharmacology

    pub_type: 杂志文章

    doi:10.1038/sj.bjp.0703904

    authors: Attucci S,Carlà V,Mannaioni G,Moroni F

    更新日期:2001-02-01 00:00:00

  • Salmeterol, a novel, long-acting beta 2-adrenoceptor agonist: characterization of pharmacological activity in vitro and in vivo.

    abstract::1. Salmeterol, a novel, long-acting beta-adrenoceptor agonist, has been compared with isoprenaline and salbutamol for activity in vitro on a range of beta-adrenoceptor containing preparations from laboratory animals and man, and in vivo for bronchodilator activity in the conscious guinea-pig. 2. Salmeterol, like isopr...

    journal_title:British journal of pharmacology

    pub_type: 杂志文章

    doi:10.1111/j.1476-5381.1991.tb12486.x

    authors: Ball DI,Brittain RT,Coleman RA,Denyer LH,Jack D,Johnson M,Lunts LH,Nials AT,Sheldrick KE,Skidmore IF

    更新日期:1991-11-01 00:00:00

  • Quantitative autoradiographic studies of relaxin binding in rat atria, uterus and cerebral cortex: characterization and effects of oestrogen treatment.

    abstract::The binding characteristics of the relaxin receptor in rat atria, uterus and cortex were studied using a [33P]-labelled human gene 2 relaxin (B33) and quantitative receptor autoradiography. The binding kinetics of [33P]-human gene 2 relaxin (B33) were investigated in slide-mounted rat atrial sections. The binding achi...

    journal_title:British journal of pharmacology

    pub_type: 杂志文章

    doi:10.1038/sj.bjp.0702517

    authors: Tan YY,Wade JD,Tregear GW,Summers RJ

    更新日期:1999-05-01 00:00:00

  • Acceleration of recovery of gastric epithelial integrity by 16,16-dimethyl prostaglandin E2.

    abstract::The effects of pretreatment with 16,16-dimethyl prostaglandin E2 (DmPGE2) on the recovery of gastric mucosal 'barrier' parameters after ethanol-induced damage were studied using an ex vivo chamber preparation in the rat. DmPGE2 (4-40 micrograms kg-1) significantly reduced the extent of haemorrhagic damage to the gastr...

    journal_title:British journal of pharmacology

    pub_type: 杂志文章

    doi:10.1111/j.1476-5381.1985.tb11105.x

    authors: Wallace JL,Whittle BJ

    更新日期:1985-12-01 00:00:00

  • Effects of phosphodiesterase inhibitors on interleukin-4 and interleukin-13 generation from human basophils.

    abstract::The aim of the present study was to determine whether inhibition of cyclic nucleotide phosphodiesterase (PDE) modulates the stimulated generation of the cytokines, interleukin-4 (IL-4) and IL-13, from human basophils. This was addressed by evaluating the effects of both nonselective and selective inhibitors of PDEs on...

    journal_title:British journal of pharmacology

    pub_type: 杂志文章

    doi:10.1038/sj.bjp.0705892

    authors: Eskandari N,Wickramasinghe T,Peachell PT

    更新日期:2004-08-01 00:00:00

  • Peripheral PACAP inhibits gastric acid secretion through somatostatin release in mice.

    abstract::1. Studies in rats suggest that PACAP modulates gastric acid secretion through the release of both histamine and somatostatin. 2. We characterized the effects of exogenous PACAP on gastric acid secretion in urethane-anesthetized mice implanted with a gastric cannula and in conscious 2-h pylorus ligated mice, and deter...

    journal_title:British journal of pharmacology

    pub_type: 杂志文章

    doi:10.1038/sj.bjp.0705739

    authors: Piqueras L,Taché Y,Martínez V

    更新日期:2004-05-01 00:00:00

  • Animal models of cannabinoid reward.

    abstract::The endogenous cannabinoid system is involved in numerous physiological and neuropsychological functions. Medications that target this system hold promise for the treatment of a wide variety of disorders. However, as reward is one of the most prominent of these functions, medications that activate this system must be ...

    journal_title:British journal of pharmacology

    pub_type: 杂志文章,评审

    doi:10.1111/j.1476-5381.2010.00775.x

    authors: Panlilio LV,Justinova Z,Goldberg SR

    更新日期:2010-06-01 00:00:00

  • Enhanced endothelin receptor type B-mediated vasodilation and underlying [Ca²⁺]i in mesenteric microvessels of pregnant rats.

    abstract:BACKGROUND AND PURPOSE:Normal pregnancy is associated with decreased vascular resistance and increased release of vasodilators. Endothelin-1 (ET-1) causes vasoconstriction via endothelin receptor type A (ET(A)R), but could activate ET(B)R in the endothelium and release vasodilator substances. However, the roles of ET(B...

    journal_title:British journal of pharmacology

    pub_type: 杂志文章

    doi:10.1111/bph.12225

    authors: Mazzuca MQ,Dang Y,Khalil RA

    更新日期:2013-07-01 00:00:00

  • The Scar-in-a-Jar: studying potential antifibrotic compounds from the epigenetic to extracellular level in a single well.

    abstract:BACKGROUND AND PURPOSE:Fibrosis, a pathological accumulation of collagen in tissues, represents a major global disease burden. Effective characterization of potential antifibrotic drugs has been constrained by poor formation of the extracellular matrix in vitro, due to tardy procollagen processing by collagen C-protein...

    journal_title:British journal of pharmacology

    pub_type: 杂志文章

    doi:10.1111/j.1476-5381.2009.00387.x

    authors: Chen CZ,Peng YX,Wang ZB,Fish PV,Kaar JL,Koepsel RR,Russell AJ,Lareu RR,Raghunath M

    更新日期:2009-11-01 00:00:00

  • Actions of cromakalim on outward currents of CA1 neurones in hippocampal slices.

    abstract::1. Membrane effects of cromakalim (Crom; 50-300 microM) were examined in CA1 neurones recorded mainly by intracellular, single-electrode voltage-clamping in slices (from Sprague-Dawley rats) kept in an interface chamber at 33 degrees C. 2. In 14 cells held at -63 +/- 3.5 mV, in the presence of tetrodotoxin, kynurenic ...

    journal_title:British journal of pharmacology

    pub_type: 杂志文章

    doi:10.1111/j.1476-5381.1994.tb17004.x

    authors: Erdemli G,Krnjević K

    更新日期:1994-10-01 00:00:00