Abstract：
:Myeloperoxidase (MPO), a member of the haem peroxidase-cyclooxygenase superfamily, is abundantly expressed in neutrophils and to a lesser extent in monocytes and certain type of macrophages. MPO participates in innate immune defence mechanism through formation of microbicidal reactive oxidants and diffusible radical species. A unique activity of MPO is its ability to use chloride as a cosubstrate with hydrogen peroxide to generate chlorinating oxidants such as hypochlorous acid, a potent antimicrobial agent. However, evidence has emerged that MPO-derived oxidants contribute to tissue damage and the initiation and propagation of acute and chronic vascular inflammatory disease. The fact that circulating levels of MPO have been shown to predict risks for major adverse cardiac events and that levels of MPO-derived chlorinated compounds are specific biomarkers for disease progression, has attracted considerable interest in the development of therapeutically useful MPO inhibitors. Today, detailed information on the structure of ferric MPO and its complexes with low- and high-spin ligands is available. This, together with a thorough understanding of reaction mechanisms including redox properties of intermediates, enables a rationale attempt in developing specific MPO inhibitors that still maintain MPO activity during host defence and bacterial killing but interfere with pathophysiologically persistent activation of MPO. The various approaches to inhibit enzyme activity of MPO and to ameliorate adverse effects of MPO-derived oxidants will be discussed. Emphasis will be put on mechanism-based inhibitors and high-throughput screening of compounds as well as the discussion of physiologically useful HOCl scavengers.
journal_name
Br J Pharmacoljournal_title
British journal of pharmacologyauthors
Malle E,Furtmüller PG,Sattler W,Obinger Cdoi
10.1038/sj.bjp.0707358subject
Has Abstractpub_date
2007-11-01 00:00:00pages
838-54issue
6eissn
0007-1188issn
1476-5381pii
0707358journal_volume
152pub_type
杂志文章,评审abstract：:Extensive in vitro and in vivo studies have shown that cannabinoid drugs have neuroprotective properties and suggested that the endocannabinoid system may be involved in endogenous neuroprotective mechanisms. On the other hand, neurotoxic effects of cannabinoids in vitro and in vivo were also described. Several possib...
journal_title：British journal of pharmacology
pub_type： 杂志文章,评审
doi：10.1111/j.1476-5381.2011.01280.x
更新日期：2011-08-01 00:00:00
abstract：:Ever increasing use of engineered carbon nanoparticles in nanopharmacology for selective imaging, sensor or drug delivery systems has increased the potential for blood platelet-nanoparticle interactions. We studied the effects of engineered and combustion-derived carbon nanoparticles on human platelet aggregation in v...
journal_title：British journal of pharmacology
pub_type： 杂志文章
doi：10.1038/sj.bjp.0706386
更新日期：2005-11-01 00:00:00
abstract：BACKGROUND AND PURPOSE:Nociceptin/orphanin FQ (N/OFQ) peptide (NOP) receptor agonists display a promising analgesic profile in preclinical studies. However, supraspinal N/OFQ produced hyperalgesia in rodents and such effects have not been addressed in primates. Thus, the aim of this study was to investigate the effects...
journal_title：British journal of pharmacology
pub_type： 杂志文章
doi：10.1111/bph.13124
更新日期：2015-07-01 00:00:00
abstract：:1 The metabolism of extracellular nucleotides plays an important role in nucleotide signalling mediated by P2 receptors. The nucleotide sequence encoding a putative human ecto-ATPase named CD39L1 was reported recently. However, the biological activity of this protein has not been established. 2 Based on the sequence o...
journal_title：British journal of pharmacology
pub_type： 杂志文章
doi：10.1038/sj.bjp.0702805
更新日期：1999-09-01 00:00:00
abstract：:Antidromic stimulation of sensory peripheral branches of the trigeminal system (mental nerve) leads to cutaneous vasodilatation and increases vascular permeability in the rat. Antidromic vasodilatation is observed only at high intensity stimulation (10 V, 15 Hz, 0.2 or 5 ms) supporting the participation of afferent C-...
journal_title：British journal of pharmacology
pub_type： 杂志文章
doi：10.1111/j.1476-5381.1985.tb16144.x
更新日期：1985-03-01 00:00:00
abstract：:1. The distribution of sympathetic adrenergic nerves on the rat middle cerebral artery and on the arterioles which originated from it was determined by use of gloxylic histochemistry. 2. Whereas the middle cerebral artery and proximal arterioles arising from this artery received a sympathetic innervation, the distal r...
journal_title：British journal of pharmacology
pub_type： 杂志文章
doi：10.1111/j.1476-5381.1989.tb11884.x
更新日期：1989-04-01 00:00:00
abstract：:1. The uptake of (3)H-digitoxin, (3)H-ouabain and (3)H-dihydro-ouabain by isolated guinea-pig atria has been studied and compared with the inhibition of the sodium pump and with the inotropic effect.2. Analysis of the curve relating the uptake of digitoxin and ouabain at equilibrium to the bath concentration enabled a...
journal_title：British journal of pharmacology
pub_type： 杂志文章
doi：10.1111/j.1476-5381.1972.tb08146.x
更新日期：1972-11-01 00:00:00
abstract：:1 In cats anaesthetized with pentobarbitone, observations were made on respiration, spontaneous and evoked diaphragmatic electromyograms, blood pressure, heart rate, indirectly-induced contractions of the anterior tibialis muscle and nictitating membrane, and electrical excitability of the inspiratory centre in the me...
journal_title：British journal of pharmacology
pub_type： 杂志文章
doi：10.1111/j.1476-5381.1980.tb07930.x
更新日期：1980-10-01 00:00:00
abstract：BACKGROUND AND PURPOSE:Varenicline, a neuronal nicotinic acetylcholine receptor (nAChR) modulator, decreases ethanol consumption in rodents and humans. The proposed mechanism of action for varenicline to reduce ethanol consumption has been through modulation of dopamine (DA) release in the nucleus accumbens (NAc) via α...
journal_title：British journal of pharmacology
pub_type： 杂志文章
doi：10.1111/bph.12690
更新日期：2014-07-01 00:00:00
abstract：BACKGROUND AND PURPOSE:We recently reported that AAV1-Rheb(S16H) transduction could protect hippocampal neurons through the induction of brain-derived neurotrophic factor (BDNF) in the rat hippocampus in vivo. It is still unclear how neuronal BDNF produced by AAV1-Rheb(S16H) transduction induces neuroprotective effects...
journal_title：British journal of pharmacology
pub_type： 杂志文章
doi：10.1111/bph.14882
更新日期：2020-02-01 00:00:00
abstract：AIMS:The trace amine-associated receptor (Taar) family displays high species- and subtype-specific pharmacology. Several trace amines such as β-phenylethylamine (β-PEA), p-tyramine and tryptamine are agonists at TA(1) but poorly activate rat and mouse Taar4. PRINCIPAL RESULTS:Using rat TA(1) and Taar4 chimera, we id...
journal_title：British journal of pharmacology
pub_type： 杂志文章
doi：10.1111/bph.12020
更新日期：2013-03-01 00:00:00
abstract：:1. The effects of long-term treatment with trandolapril, an angiotensin I-converting enzyme inhibitor, on exercise capacity of rats with chronic heart failure (CHF) following coronary artery ligation were examined. CHF was developed by 8 weeks after the coronary artery ligation. 2. The running time of rats with CHF in...
journal_title：British journal of pharmacology
pub_type： 杂志文章
doi：10.1038/sj.bjp.0702471
更新日期：1999-04-01 00:00:00
abstract：:1. Rabbit left atrial preparations driven electrically at different rates were used for studies on inotropic effects of cations, drugs and coupled pacing. Sino-atrial node-atrial preparations were used for investigating the chronotropic effect of noradrenaline.2. The contractile tension-driving rate relationship was m...
journal_title：British journal of pharmacology
pub_type： 杂志文章
doi：10.1111/j.1476-5381.1969.tb09510.x
更新日期：1969-06-01 00:00:00
abstract：:Three neurotoxin homologues (CM10 and CM12 from Naja haje annulifera and S5C10 from Dendroaspis jamesoni kaimosae) and two short neurotoxins (CM14 from Naja haje annulifera and erabutoxin b from Laticauda semifasciata) were examined by circular dichroism (c.d.) and tested for neuromuscular activity on chick biventer c...
journal_title：British journal of pharmacology
pub_type： 杂志文章
doi：10.1111/j.1476-5381.1984.tb10810.x
更新日期：1984-07-01 00:00:00
abstract：:1. Transcriptional control of the human beta(2) adrenergic receptor gene (ADRB2) predominantly resides within a 549 base pair region immediately 5' to the start of translation. Within this region, four naturally occurring polymorphisms, -468 C-->G, -367 T-->C, -47 T-->C, and -20 T-->C, have been identified. 2. To dete...
journal_title：British journal of pharmacology
pub_type： 杂志文章
doi：10.1038/sj.bjp.0704935
更新日期：2002-12-01 00:00:00
abstract：:The effects of intravenous sufentanil and pre-administration of N-methyl-D-aspartate (NMDA) receptor antagonists were tested on a reflex triggered by C-fibre activation. The reflex was elicited by electrical stimulation of the sural nerve and recorded from the ipsilateral biceps femoris muscle in halothane anaesthetiz...
journal_title：British journal of pharmacology
pub_type： 杂志文章
doi：10.1038/sj.bjp.0704148
更新日期：2001-08-01 00:00:00
abstract：:1. In order to determine whether the renin-angiotensin system is involved in myocardial ischaemia-reperfusion injury, we investigated and compared the effects on infarct size of two different drugs which interfere with this system, i.e., an angiotensin II (AT1) antagonist, EXP3174, and an angiotensin I-converting enzy...
journal_title：British journal of pharmacology
pub_type： 杂志文章
doi：10.1111/j.1476-5381.1993.tb13908.x
更新日期：1993-11-01 00:00:00
abstract：BACKGROUND AND PURPOSE:Alogliptin, a highly selective dipeptidyl peptidase-4 (DPP-4) inhibitor, enhances incretin action and pioglitazone enhances hepatic and peripheral insulin actions. Here, we have evaluated the effects of combining these agents in diabetic mice. EXPERIMENTAL APPROACH:Effects of short-term treatmen...
journal_title：British journal of pharmacology
pub_type： 杂志文章
doi：10.1111/j.1476-5381.2009.00145.x
更新日期：2009-06-01 00:00:00
abstract：:1. The effects of intracameral injections of prostaglandins E(1), E(2), F(1a), F(2a), and A(1) were studied on the intraocular pressure (IOP) of rabbits anaesthetized with urethane.2. With the exception of prostaglandin F(1a), all the prostaglandins studied were found to be capable of producing a large, sustained rise...
journal_title：British journal of pharmacology
pub_type： 杂志文章
doi：10.1111/j.1476-5381.1969.tb09533.x
更新日期：1969-09-01 00:00:00
abstract：BACKGROUND AND PURPOSE:Cholecystokinin (CCK) stimulates the release of amylase and lipase from the normal pancreas. However, it is not clear to what extent this occurs in the early stages of pancreatitis induced by biliary tract obstruction in the rat and whether CCK initiates an inflammatory cascade in this condition....
journal_title：British journal of pharmacology
pub_type： 杂志文章
doi：10.1038/bjp.2008.44
更新日期：2008-04-01 00:00:00
abstract：:1. The mechanisms underlying the postjunctional blockade induced by phenthonium [N-(4-phenyl) phenacyl 1-hyoscyamine] were investigated in mammalian and amphibian muscles. This muscarinic antagonist was previously shown to enhance specifically the spontaneous acetylcholine (ACh) release at concentrations that blocked ...
journal_title：British journal of pharmacology
pub_type： 杂志文章
doi：10.1038/sj.bjp.0701932
更新日期：1998-07-01 00:00:00
abstract：:1. Sarcolemmal membranes were isolated from normal and from denervated muscles and the specific binding of [125I]-alpha-bungarotoxin to the membranes was determined. 2. Cytosol prepared from either slow (soleus) or fast (extensor digitorum longus) muscle increased the toxin binding. Similar effects were seen with cyto...
journal_title：British journal of pharmacology
pub_type： 杂志文章
doi：10.1111/j.1476-5381.1988.tb11611.x
更新日期：1988-07-01 00:00:00
abstract：:1 delta'-trans-Tetrahydrocannabinol (THC) is more active orally in mice than previously thought, as cataleptic responses occur at doses from 0.06 mg/kg upwards, with peak activity at 2 to 4 h after dosing. These doses and peaks correspond well with the effects in man. 2 Comparison with chlorpromazine in mice shows tha...
journal_title：British journal of pharmacology
pub_type： 杂志文章
doi：10.1111/j.1476-5381.1979.tb08691.x
更新日期：1979-11-01 00:00:00
abstract：:1. The effects of purinergic stimulation on action potential, force of contraction, 86Rb efflux and 45Ca uptake were investigated in guinea-pig left atria. 2. Adenosine exerted a negative inotropic effect which was antagonized by adenosine deaminase but enhanced by dipyridamole. 3. The negative inotropic effect of ade...
journal_title：British journal of pharmacology
pub_type： 杂志文章
doi：10.1111/j.1476-5381.1989.tb12577.x
更新日期：1989-08-01 00:00:00
abstract：:1. Simultaneous computer modelling of control and guanfacine-masked [3H]-MK 912 saturation curves as well as guanfacine competition curves revealed that the drugs bound to two alpha 2-adrenoceptor subtypes in the rat cerebral cortex with very different selectivities. These alpha 2-adrenoceptor subtypes were designated...
journal_title：British journal of pharmacology
pub_type： 杂志文章
doi：10.1111/j.1476-5381.1992.tb14446.x
更新日期：1992-08-01 00:00:00
abstract：:1. This study investigated whether a single administration of a range of doses (1, 4 and 8 mg kg-1, i.p.) of paroxetine, citalopram or venlafaxine may simultaneously increase extracellular levels of 5-HT ([5-HT]ext) and noradrenaline ([NA]ext) by using in vivo microdialysis in the frontal cortex (FCx) of awake, freely...
journal_title：British journal of pharmacology
pub_type： 杂志文章
doi：10.1038/sj.bjp.0705538
更新日期：2003-11-01 00:00:00
abstract：BACKGROUND AND PURPOSE:β-Adrenoceptor stimulation induces glucose uptake in several insulin-sensitive tissues by poorly understood mechanisms. EXPERIMENTAL APPROACH:We used a model system in CHO-K1 cells expressing the human β(2)-adrenoceptor and glucose transporter 4 (GLUT4) to investigate the signalling mechanisms i...
journal_title：British journal of pharmacology
pub_type： 杂志文章
doi：10.1111/j.1476-5381.2011.01647.x
更新日期：2012-03-01 00:00:00
abstract：:1. The electrical activity of guinea-pig pelvic ganglion cells following iontophoretically applied cholinergic drugs, alone and during orthodromic nerve stimulation via the hypogastric nerve, has been recorded intracellularly.2. Iontophoretic application of nicotine (Nic) and acetylcholine (ACh) reduced membrane resis...
journal_title：British journal of pharmacology
pub_type： 杂志文章
doi：10.1111/j.1476-5381.1971.tb09932.x
更新日期：1971-01-01 00:00:00
abstract：:The physiological regulation of the immune system encompasses comprehensive anti-inflammatory mechanisms that can be harnessed for the treatment of infectious and inflammatory disorders. Recent studies indicate that the vagal nerve, involved in control of heart rate, hormone secretion and gastrointestinal motility, is...
journal_title：British journal of pharmacology
pub_type： 杂志文章,评审
doi：10.1038/sj.bjp.0707264
更新日期：2007-08-01 00:00:00
abstract：BACKGROUND AND PURPOSE:In small arteries, small conductance Ca²⁺-activated K⁺ channels (SK(Ca)) and intermediate conductance Ca²⁺-activated K⁺ channels (IK(Ca)) restricted to the vascular endothelium generate hyperpolarization that underpins the NO- and PGI₂-independent, endothelium-derived hyperpolarizing factor respo...
journal_title：British journal of pharmacology
pub_type： 杂志文章
doi：10.1111/bph.12160
更新日期：2013-06-01 00:00:00
