Abstract:
:1. We have evaluated the selectivity of ketoprofen and two novel nonsteroidal anti-inflammatory drugs, N-[2-(cyclohexyloxy)-4-nitrophenyl]methanesulphonamide (NS-398) and 5-methanesulphonamido-6-(2,4-difluorothiophenyl)-1-indano ne (L-745,337), in inhibiting the cyclo-oxygenase activity of prostaglandin endoperoxide synthase-2 (PGHS-2) vs PGHS-1 in human blood monocytes and platelets, respectively. 2. Heparinized whole blood samples were drawn from healthy volunteers pretreated with aspirin, 300 mg 48 h before sampling, to suppress the activity of platelet PGHS-1 and incubated at 37 degrees C for 24 h with increasing concentrations of the test compounds in the presence of lipopolysaccharide (LPS, 10 micrograms ml-1). Immunoreactive PGE2 levels were measured in plasma by a specific radioimmunoassay as an index of the cyclo-oxygenase activity of LPS-induced monocyte PGHS-2. 3. The effects of the same inhibitors on platelet PGHS-1 activity were assessed by allowing whole blood samples, drawn from the same subjects in aspirin-free periods, to clot at 37 degrees C for 1 h in the presence of the compounds and measuring immunoreactive thromboxane B2 (TXB2) levels in serum by a specific radioimmunoassay. 4. Under these experimental conditions, ketoprofen enantioselectively inhibited the cyclo-oxygenase activity of both PGHS-1 and PGHS-2 with equal potency (IC50 ratio: approx. 0.5 for both enantiomers), while L-745,337 and NS-398 achieved selective inhibition of monocyte PGHS-2 (IC50 ratio: > 150). L-745,337 and NS-398 did not affect LPS-induced monocyte PGHS-2 biosynthesis to any detectable extent. 5. We conclude that L-745,337 and NS-398 are selective inhibitors of the cyclo-oxygenase activity of human monocyte PGHS-2. These compounds may provide adequate tools to test the contribution of this novel pathway of arachidonate metabolism to human inflammatory disease.
journal_name
Br J Pharmacoljournal_title
British journal of pharmacologyauthors
Panara MR,Greco A,Santini G,Sciulli MG,Rotondo MT,Padovano R,di Giamberardino M,Cipollone F,Cuccurullo F,Patrono Cdoi
10.1111/j.1476-5381.1995.tb15091.xsubject
Has Abstract,Author List Incompletepub_date
1995-11-01 00:00:00pages
2429-34issue
5eissn
0007-1188issn
1476-5381journal_volume
116pub_type
杂志文章abstract::1. By use of a number of analogues of adenine nucleotides, the structure-activity relationships of the human platelet receptor for adenosine 5'-diphosphate (ADP) mediating increases in intracellular calcium were investigated, and compared with the known structure-activity relationships for induction by ADP of platelet...
journal_title:British journal of pharmacology
pub_type: 杂志文章
doi:10.1111/j.1476-5381.1993.tb12869.x
更新日期:1993-03-01 00:00:00
abstract::1. Behavioural activity (delayed differentiation and spatial delayed alternation) and pharmacokinetics of diazepam and its metabolites, N-desmethyldiazepam (nordiazepam), 3-hydroxydiazepam (temazepam) and 3-hydroxy-N-desmethyldiazepam (oxazepam), and of dipotassium clorazepate (clorazepate), were studied in the monkey...
journal_title:British journal of pharmacology
pub_type: 杂志文章
doi:10.1111/j.1476-5381.1977.tb08423.x
更新日期:1977-11-01 00:00:00
abstract::Synaptic transmission in the isolated olfactory cortex slice from the rat was monitored by recording the surface field potentials evoked on lateral olfactory tract (LOT) stimulation. Catechol (approximately 0.05 to 2 mM) caused a concentration-dependent, partially reversible increase in the amplitudes of all field pot...
journal_title:British journal of pharmacology
pub_type: 杂志文章
doi:10.1111/j.1476-5381.1986.tb10221.x
更新日期:1986-06-01 00:00:00
abstract::The effects of vasoactive substances on mean circulatory filling pressure (MCFP), an index of total body venous tone, were determined in conscious rats. Cumulative doses of saline (0.9% w/v NaCl solution), methoxamine (alpha 1-adrenoceptor agonist), B-HT920 (alpha 2-adrenoceptor agonist) noradrenaline and vasopressin,...
journal_title:British journal of pharmacology
pub_type: 杂志文章
doi:10.1111/j.1476-5381.1986.tb10272.x
更新日期:1986-10-01 00:00:00
abstract::There is evidence that cannabinoid-based medicines that are selective for different targets in the cannabinoid signalling system (e.g. receptors, inactivation mechanism, enzymes) might be beneficial in basal ganglia disorders, namely Parkinson's disease (PD) and Huntington's disease (HD). These benefits not only inclu...
journal_title:British journal of pharmacology
pub_type: 杂志文章,评审
doi:10.1111/j.1476-5381.2008.00088.x
更新日期:2009-04-01 00:00:00
abstract::The alpha2-adrenoceptor function in mesenteric arteries of spontaneously hypertensive rats (SHR) was investigated by comparing membrane potential changes in response to adrenergic agonists in preparations from female SHR, Wistar-Kyoto (WKY) and normotensive Wistar rats (NWR). Resting membrane potential was found to be...
journal_title:British journal of pharmacology
pub_type: 杂志文章
doi:10.1038/sj.bjp.0702177
更新日期:1998-11-01 00:00:00
abstract::1. The endothelium-dependent relaxants acetylcholine (ACh; 0.03-10 microM) and A23187 (0.03-10 microM), and nitric oxide (NO), applied either as authentic NO (0.01-10 microM) or as the NO donors 3-morpholino-sydnonimine (SIN-1; 0.1-10 microM) and S-nitroso-N-acetylpenicillamine (SNAP; 0.1-10 microM), each evoked conce...
journal_title:British journal of pharmacology
pub_type: 杂志文章
doi:10.1038/sj.bjp.0701746
更新日期:1998-04-01 00:00:00
abstract:BACKGROUND AND PURPOSE:The two longest C-termini of the purinergic P2X receptors occur in the P2X2 and P2X7 receptors and are thought to interact with multiple cytoplasmic proteins, among which are members of the cytoskeleton, including microtubules. In this work we asked whether disrupting the microtubule cytoskeleton...
journal_title:British journal of pharmacology
pub_type: 杂志文章
doi:10.1111/j.1476-5381.2011.01254.x
更新日期:2011-07-01 00:00:00
abstract::1. U937 cells are a continuous line of human cells of committed monocytic origin which serve as a useful model for studying human monocytic function. The present study investigated the effect of platelet-activating factor (Paf) on intracellular free calcium ion concentration ([Ca2+]i) in U937 cells using the calcium f...
journal_title:British journal of pharmacology
pub_type: 杂志文章
doi:10.1111/j.1476-5381.1988.tb11461.x
更新日期:1988-04-01 00:00:00
abstract::1. Dose-dependent vasodilator responses to dopamine, isoprenaline, noradrenaline, 3-isobutyl-1-methylxanthine (IBMX) and sodium nitroprusside were obtained in isolated perfused mesentery preparations, taken from reserpine-treated rats of different ages. The preparations were pretreated with phenoxybenzamine (1 microM)...
journal_title:British journal of pharmacology
pub_type: 杂志文章
doi:10.1111/j.1476-5381.1989.tb16895.x
更新日期:1989-09-01 00:00:00
abstract::1 The L6 myocyte cell line expresses high affinity receptors for calcitonin gene-related peptide (CGRP) which are coupled to activation of adenylyl cyclase. The biochemical pharmacology of these receptors has been examined by radioligand binding or adenosine 3':5'-cyclic monophosphate (cyclic AMP) accumulation. 2 In i...
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pub_type: 杂志文章
doi:10.1111/j.1476-5381.1992.tb14272.x
更新日期:1992-02-01 00:00:00
abstract:BACKGROUND & PURPOSE:The therapeutically available quinolone antibiotic moxifloxacin has been used as a positive control for prolonging the QT interval in both clinical and non-clinical studies designed to assess the potential of new drugs to delay cardiac repolarization. Despite moxifloxacin prolonging QT, it has not ...
journal_title:British journal of pharmacology
pub_type: 杂志文章
doi:10.1038/sj.bjp.0706900
更新日期:2006-12-01 00:00:00
abstract:BACKGROUND AND PURPOSE:(R,S)-ketamine produces rapid and significant antidepressant effects in approximately 65% of patients suffering from treatment-resistant bipolar depression (BD). The genetic, pharmacological and biochemical differences between ketamine responders and non-responders have not been identified. The p...
journal_title:British journal of pharmacology
pub_type: 杂志文章,随机对照试验
doi:10.1111/bph.12494
更新日期:2014-04-01 00:00:00
abstract::1--Responses (relaxation) to the beta-adrenoceptor agonists, isoprenaline, fenoterol or noradrenaline, were obtained on cat tracheal preparations contracted with a submaximal concentration of carbachol (0.5 microM). 2--The relative potencies of isoprenaline: fenoterol: noradrenaline were 100:8.1:10.7. From this, it wa...
journal_title:British journal of pharmacology
pub_type: 杂志文章
doi:10.1111/j.1476-5381.1983.tb09406.x
更新日期:1983-02-01 00:00:00
abstract::1. The regulatory mechanism for the hypertrophy of skeletal muscles induced by clenbuterol is unclear. The purpose of the present study was to determine the extent to which transforming growth factor betas (TGFbetas), fibroblast growth factors (FGFs), hepatocyte growth factor (HGF), and platelet-derived growth factors...
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pub_type: 杂志文章
doi:10.1038/sj.bjp.0706625
更新日期:2006-02-01 00:00:00
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journal_title:British journal of pharmacology
pub_type: 杂志文章
doi:10.1111/j.1476-5381.1979.tb07871.x
更新日期:1979-04-01 00:00:00
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pub_type: 杂志文章
doi:10.1111/j.1476-5381.1994.tb13075.x
更新日期:1994-06-01 00:00:00
abstract::1. To investigate the underlying mechanism for the angiotensin II-induced desensitization of the contractile response during the prolonged stimulation of the vascular smooth muscle, we determined the effects of angiotensin-II on (1) cytosolic Ca2+ concentration ([Ca2+]i) and tension using fura-2-loaded medial strips o...
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更新日期:2000-02-01 00:00:00
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pub_type: 杂志文章
doi:10.1038/sj.bjp.0703062
更新日期:2000-01-01 00:00:00
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pub_type: 杂志文章
doi:10.1111/j.1476-5381.1981.tb10471.x
更新日期:1981-11-01 00:00:00
abstract:BACKGROUND AND PURPOSE:Down's syndrome is a common genetic cause of intellectual disability, for which there are no drug therapies. Mechanistic studies in a model of Down's syndrome [Ts65Dn (TS) mice] demonstrated that impaired cognitive function was due to excessive neuronal inhibitory tone. These deficits were normal...
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pub_type: 杂志文章
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更新日期:2013-07-01 00:00:00
abstract::1. In mouse triangularis sterni nerve-muscle preparations, reduced extracellular Na+ concentrations and low concentrations of the Na+ channel blocking toxins tetrodotoxin (TTX, 18-36 nM) and mu-conotoxin GIIIB (0.4-2.0 microM) selectively decreased the amplitude of the component of perineural waveforms associated with...
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更新日期:1992-05-01 00:00:00
abstract::1. The subtype of alpha1-adrenoceptor mediating contractions to phenylephrine of the rat thoracic aorta, mesenteric artery and pulmonary artery were investigated by use of antagonists which show selectivity between the cloned alpha1-adrenoceptor subtypes in binding studies. 2. Cumulative concentration-contraction curv...
journal_title:British journal of pharmacology
pub_type: 杂志文章
doi:10.1038/sj.bjp.0701461
更新日期:1997-11-01 00:00:00
abstract::The discovery of an additional duplicated alpha-2 adrenoceptor subtype in the zebrafish raises a pesky nomenclature issue, as well as questions about the functions of the alpha-2 adrenoceptors in the zebrafish and how many alpha-2 receptors does an organism really need. ...
journal_title:British journal of pharmacology
pub_type: 评论,杂志文章,评审
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更新日期:2005-01-01 00:00:00
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pub_type: 杂志文章
doi:10.1111/j.1476-5381.1974.tb09610.x
更新日期:1974-03-01 00:00:00
abstract::1. The radioligand binding characteristics of the 3H-derivative of the novel 5-HT3 receptor antagonist BRL46470 were investigated and directly compared to the well characterized 5-HT3 receptor radioligand [3H]-granisetron, in tissue homogenates prepared from rat cerebral cortex/hippocampus, rat ileum, NG108-15 cells, ...
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pub_type: 杂志文章
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更新日期:1995-09-01 00:00:00
abstract:BACKGROUND AND PURPOSE:Inhibitors of histone deacetylase (HDAC) are emerging as a promising class of anti-cancer drugs, but a generic deregulation of transcription in neoplastic cells cannot fully explain their therapeutic effects. In this study we evaluated alternative molecular mechanisms by which HDAC inhibitors cou...
journal_title:British journal of pharmacology
pub_type: 杂志文章
doi:10.1038/sj.bjp.0707608
更新日期:2008-02-01 00:00:00
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pub_type: 杂志文章
doi:10.1111/j.1476-5381.1985.tb08852.x
更新日期:1985-05-01 00:00:00
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journal_title:British journal of pharmacology
pub_type: 杂志文章
doi:10.1111/bph.13031
更新日期:2015-04-01 00:00:00
abstract:BACKGROUND AND PURPOSE:Sepsis is a systemic inflammatory response accompanied by excessive production of inflammatory cytokines and cardiovascular dysfunction. Importantly, macrophage-derived pro-inflammatory agents play a key role in cardiovascular impairment in sepsis. Here we have investigated the effects of trimeta...
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pub_type: 杂志文章
doi:10.1111/bph.13386
更新日期:2016-02-01 00:00:00