Abstract：
BACKGROUND AND PURPOSE:Arachidonyl trifluoromethyl ketone (ATK) is widely used as an inhibitor of cytosolic group IV phospholipase A(2) (cPLA(2)) and calcium-independent group VI phospholipase A(2) (iPLA(2)). ATK thus reduces arachidonic acid (AA) substrate for cyclooxygenase (COX; also known as prostaglandin H synthase) and attenuates prostaglandin (PG) synthesis. It has been shown previously, that ATK blocks thromboxane B(2) production induced by exogenous AA in human platelets. It remains, however, unknown whether ATK also directly modulates the activity of cyclooxygenase (COX). EXPERIMENTAL APPROACH:Time courses for inhibition of COX by ATK was obtained using osteoblast-like MC3T3-E1 cells, with exogenous AA as substrate and the pure enzymes COX-1 and COX-2. PGE(2) was measured by GC-MS. KEY RESULTS:ATK was a potent inhibitor of COX-1 and COX-2 with IC(50) values of 0.5 and 0.1 microM in MC3T3-E1 cells and of 1.7 and 2.6 microM using the pure enzymes. Inhibition was reversible, with slow- and tight-binding characteristics. The arachidonyl carbon chain was essential, as the saturated palmitoyl analogue had no effect. CONCLUSIONS AND IMPLICATIONS:Attenuation of PG synthesis by ATK is taken to be the consequence of PLA(2) inhibition and the findings of many studies are interpreted on that basis. If there are, however, alternative routes for AA liberation (such as phospholipase C/diacyl glycerol lipase or phospholipase D), this interpretation can lead to false conclusions. As ATK is a widely used and important pharmacological tool in eicosanoid research, knowledge of its interactions with other major enzymes of the cascade is of considerable importance.
journal_name
Br J Pharmacoljournal_title
British journal of pharmacologyauthors
Leis HJ,Windischhofer Wdoi
10.1038/bjp.2008.304subject
Has Abstractpub_date
2008-11-01 00:00:00pages
731-7issue
5eissn
0007-1188issn
1476-5381pii
bjp2008304journal_volume
155pub_type
杂志文章abstract：:1. Muscarinic receptors mediating contraction of the rat urinary bladder were characterized functionally in vitro by use of atropine, 4-diphenylacetoxy-N-methylpiperidine methiodide (4-DAMP methiodide), 4-diphenylacetoxy-N-(2-chloroethyl)-piperidine hydrochloride (4-DAMP mustard), hexahydro-sila-diphenidol hydrochlori...
journal_title：British journal of pharmacology
pub_type： 杂志文章
doi：10.1111/j.1476-5381.1995.tb15065.x
更新日期：1995-10-01 00:00:00
abstract：:1. The effects of drugs and altering stimulus parameters on neurogenic responses to electrical field stimulation (EFS) have been investigated in distal and proximal portions of the guinea-pig trachea. 2. In the presence of indomethacin (3 microM) and propranolol (1 microM) two contractile phases were evident in both t...
journal_title：British journal of pharmacology
pub_type： 杂志文章
doi：10.1111/j.1476-5381.1990.tb14174.x
更新日期：1990-12-01 00:00:00
abstract：:1. The effectiveness of alpha 1- and alpha 2-adrenoceptor activation was compared at different levels of the saphenous and cephalic vein of the dog in vitro. 2. Helically cut strips were used to determine concentration-response curves to phenylephrine, noradrenaline, UK-14,304 (5-bromo-6-(imidazoline-2-ylamino)-quinox...
journal_title：British journal of pharmacology
pub_type： 杂志文章
doi：10.1111/j.1476-5381.1990.tb12719.x
更新日期：1990-10-01 00:00:00
abstract：:1. The role of chloride concentration in modulating vasoconstrictor responses of the rat isolated kidney, perfused with Krebs-Henseleit solution, to angiotensin II (AII), arginine vasopressin (AVP) and phenylephrine (PE) was investigated. 2. Reduction of perfusate chloride from a high (117 mM) to low (87 mM) concentra...
journal_title：British journal of pharmacology
pub_type： 杂志文章
doi：10.1111/j.1476-5381.1993.tb13447.x
更新日期：1993-01-01 00:00:00
abstract：:1. The effect of clofibrate (CFB), bezafibrate (BFB), and gemfibrozil (GFB) on plasma lipoprotein (VLDL and LDL) concentration, composition and resistance to copper-induced oxidation has been studied in male Sprague-Dawley rats after a 15 day treatment. 2. Plasma triglyceride levels were reduced by CFB (41%) and BFB (...
journal_title：British journal of pharmacology
pub_type： 杂志文章
doi：10.1111/j.1476-5381.1996.tb16710.x
更新日期：1996-03-01 00:00:00
abstract：:1. The involvement of peripheral nitric oxide (NO) in febrigenic signaling to the brain has been proposed because peripherally administered NO synthase (NOS) inhibitors attenuate lipopolysaccharide (LPS)-induced fever in rodents. However, how the unstable molecule of NO can reach the brain to trigger fever is unclear....
journal_title：British journal of pharmacology
pub_type： 杂志文章
doi：10.1038/sj.bjp.0705713
更新日期：2004-04-01 00:00:00
abstract：BACKGROUND AND PURPOSE:Glucagon-like peptide-1 (GLP-1) is an incretin hormone that regulates insulin biosynthesis and secretion in a glucose-dependent manner and has been reported to induce vasodilatation. Here, we examined the possible vasorelaxant effect of GLP-1 and its underlying mechanisms. EXPERIMENTAL APPROACH:...
journal_title：British journal of pharmacology
pub_type： 杂志文章
doi：10.1111/bph.14534
更新日期：2019-02-01 00:00:00
abstract：:1. The possible roles of endothelial and smooth muscle cell hyperpolarization and nitric oxide (NO) in endothelium-dependent relaxation were examined in isolated rings of pig right coronary artery. 2. The effects of hyperpolarization were prevented with high K+ (30-125 mM), isotonic Krebs solutions. Functional antagon...
journal_title：British journal of pharmacology
pub_type： 杂志文章
doi：10.1111/j.1476-5381.1994.tb13110.x
更新日期：1994-06-01 00:00:00
abstract：:The endoplasmic reticulum (ER) is an important intracellular membranous organelle. Previous studies have demonstrated that the ER is responsible for protein folding and trafficking, lipid synthesis and the maintenance of calcium homeostasis. Interestingly, the morphology and structure of the ER were recently found to ...
journal_title：British journal of pharmacology
pub_type： 杂志文章,评审
doi：10.1111/bph.13651
更新日期：2016-12-01 00:00:00
abstract：BACKGROUND AND PURPOSE:Rosiglitazone is an anti-diabetic drug improving insulin sensitivity and glucose uptake in skeletal muscle and adipose tissues. However, several recent clinical trials suggest that rosiglitazone can increase the risk of cardiovascular ischaemia, although other studies failed to show such risks. T...
journal_title：British journal of pharmacology
pub_type： 杂志文章
doi：10.1111/j.1476-5381.2011.01539.x
更新日期：2011-12-01 00:00:00
abstract：:1. The possibility that a purine nucleotide is involved in excitatory transmission to the urinary bladder has been tested. All the purine compounds tested which contained a pyrophosphate bond produced contraction, adenosine triphosphate (ATP) being the most potent. Adenosine and adenosine monophosphate caused relaxati...
journal_title：British journal of pharmacology
pub_type： 杂志文章
doi：10.1111/j.1476-5381.1972.tb07283.x
更新日期：1972-03-01 00:00:00
abstract：:Liver X receptors (LXRs) are members of the nuclear receptor superfamily that are canonically activated by oxidized derivatives of cholesterol. Since the mid-90s, numerous groups have identified LXRs as endocrine receptors that are involved in the regulation of various physiological functions. As a result, when their ...
journal_title：British journal of pharmacology
pub_type： 杂志文章,评审
doi：10.1111/bph.15286
更新日期：2020-10-20 00:00:00
abstract：:1. Human mast cell tryptase appears to display considerable variation in activating proteinase-activated receptor 2 (PAR(2)). We found tryptase to be an inefficient activator of wild-type rat-PAR(2) (wt-rPAR(2)) and therefore decided to explore the factors that may influence tryptase activation of PAR(2). 2. Using a 2...
journal_title：British journal of pharmacology
pub_type： 杂志文章
doi：10.1038/sj.bjp.0704303
更新日期：2001-10-01 00:00:00
abstract：BACKGROUND AND PURPOSE:Humanized mice for the nuclear receptor peroxisome proliferator-activated receptor δ (PPARδ), termed PPARδ knock-in (PPARδ KI) mice, were generated for the investigation of functional differences between mouse and human PPARδ and as tools for early drug efficacy assessment. EXPERIMENTAL APPROACH...
journal_title：British journal of pharmacology
pub_type： 杂志文章
doi：10.1111/j.1476-5381.2011.01359.x
更新日期：2011-09-01 00:00:00
abstract：:The kallikrein-kinin system is subdivided into the plasma and tissue-kallikrein-kinin system, with bradykinin (BK) and kallidin (KAL) (Lys(0)-bradykinin) as functional peptides. This occurs in both humans and other mammals. Both peptides are released by plasma and tissue-kallikrein. BK, but not KAL, has been detected ...
journal_title：British journal of pharmacology
pub_type： 杂志文章
doi：10.1038/sj.bjp.0706409
更新日期：2005-12-01 00:00:00
abstract：:1. We have investigated the effects of the selective phosphodiesterase (PDE) type 4 inhibitor, rolipram (0.01-1 microM) on cytosolic Ca2+ fluxes in FMLP-activated human neutrophils, as well as on superoxide production by, and release of elastase from, these cells. 2. Cytosolic Ca2+ fluxes were measured by use of fura-...
journal_title：British journal of pharmacology
pub_type： 杂志文章
doi：10.1038/sj.bjp.0701849
更新日期：1998-06-01 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：:The mechanism underlying the LTC(4)-induced contraction of guinea-pig taenia coli was determined using the simultaneous measurements of [Ca(2+)](i) and force in whole muscle preparations. Additional experiments were performed in receptor coupled permeabilized preparation. For comparison purposes, the contraction which...
journal_title：British journal of pharmacology
pub_type： 杂志文章
doi：10.1038/sj.bjp.0704122
更新日期：2001-06-01 00:00:00
abstract：BACKGROUND AND PURPOSE:Cytochrome P450 (CYP, P450) 3A4 is involved in the metabolism of 50% of drugs and its catalytic activity in vivo is not explained only by hepatic expression levels. We previously demonstrated that UDP-glucuronosyltransferase (UGT) 2B7 suppressed CYP3A4 activity through an interaction. In the pres...
journal_title：British journal of pharmacology
pub_type： 杂志文章
doi：10.1111/bph.14900
更新日期：2020-03-01 00:00:00
abstract：:Arterial stiffness progressively increases with aging and is an independent predictor of cardiovascular disease (CVD) risk. Evidence supports that there are sex differences in the time course of aging-related arterial stiffness and the associated CVD risk, which increases disproportionately in postmenopausal women. Th...
journal_title：British journal of pharmacology
pub_type： 杂志文章,评审
doi：10.1111/bph.14624
更新日期：2019-11-01 00:00:00
abstract：BACKGROUND AND PURPOSE:Baclofen (a GABA(B) receptor agonist) is the most commonly used anti-spasticity agent in clinical practice. While effective when administered spinally or systemically, the development of progressive tolerance represents a serious limitation for its long-term use. The goal of the present study was...
journal_title：British journal of pharmacology
pub_type： 杂志文章
doi：10.1111/j.1476-5381.2010.00954.x
更新日期：2010-11-01 00:00:00
abstract：BACKGROUND AND PURPOSE:We determined the effects of treatment with LR-90, an inhibitor of advanced glycation end products, on the mechanical properties of the arterial system in streptozotocin (STZ)-induced diabetic Sprague Dawley rats, using aortic impedance analysis, and further investigated the effects of LR-90 on t...
journal_title：British journal of pharmacology
pub_type： 杂志文章
doi：10.1111/bph.12656
更新日期：2014-06-01 00:00:00
abstract：:Glycogen synthase kinase 3 (GSK3), a constitutively acting multi-functional serine threonine kinase is involved in diverse physiological pathways ranging from metabolism, cell cycle, gene expression, development and oncogenesis to neuroprotection. These diverse multiple functions attributed to GSK3 can be explained by...
journal_title：British journal of pharmacology
pub_type： 杂志文章,评审
doi：10.1111/j.1476-5381.2008.00085.x
更新日期：2009-03-01 00:00:00
abstract：BACKGROUND AND PURPOSE:Gut microbiota plays an important role in type 2 diabetes mellitus (T2DM) progression. From our previous work N-(4-Hydroxyphenethyl)-3-mercapto-2-methylpropanamide (HMPA) is a potential T2DM drug. We evaluated the effect of HMPA on gut microbiota and studied the molecular mechanism underlying HMP...
journal_title：British journal of pharmacology
pub_type： 杂志文章
doi：10.1111/bph.15338
更新日期：2020-12-07 00:00:00
abstract：BACKGROUND AND PURPOSE:Cannabis extracts and several cannabinoids have been shown to exert broad anti-inflammatory activities in experimental models of inflammatory CNS degenerative diseases. Clinical use of many cannabinoids is limited by their psychotropic effects. However, phytocannabinoids like cannabidiol (CBD), d...
journal_title：British journal of pharmacology
pub_type： 杂志文章
doi：10.1111/j.1476-5381.2011.01379.x
更新日期：2011-08-01 00:00:00
abstract：BACKGROUND AND PURPOSE:Insulin resistance is often found to be associated with high blood pressure. We propose that in insulin-resistant hypertension, endothelial dysfunction is the consequence of increased activity of vascular MMP-2. As MMP-2 proteolytically cleaves a number of extracellular matrix proteins, we hypoth...
journal_title：British journal of pharmacology
pub_type： 杂志文章
doi：10.1111/j.1476-5381.2011.01583.x
更新日期：2012-02-01 00:00:00
abstract：:1 N-2-Chlorethyl-N-ethyl-2-bromobenzylamine hydrochloride (DSP 4) 50 mg/kg intraperitoneally, produced a long-term decrease in the capacity of brain homogenates to accumulate noradrenaline with significant effect 8 months after the injection. It had no effect on the noradrenaline uptake in homogenates from the striatu...
journal_title：British journal of pharmacology
pub_type： 杂志文章
doi：10.1111/j.1476-5381.1976.tb08619.x
更新日期：1976-12-01 00:00:00
abstract：:1. 2-2' Pyridylisatogen tosylate (PIT) (greater than 2.5 muM) relaxed the guinea-pig isolated taenia caeci by an unknown mechanism. 2. With higher concentrations of PIT (greater than 12.5 muM) subsequent applications of adenosine 5'-triphosphate (ATP) (2-600 muM) revealed a blockade of the ATP receptors. The antagonis...
journal_title：British journal of pharmacology
pub_type： 杂志文章
doi：10.1111/j.1476-5381.1975.tb07397.x
更新日期：1975-04-01 00:00:00
abstract：:The concentration-dependence of the negative and positive inotropic effect of choline esters and of oxotremorine was studied in isometrically contracting papillary muscles of the guinea-pig. The preparations were obtained from reserpine-pretreated animals and were electrically driven at a frequency of 0.2 Hz. In the p...
journal_title：British journal of pharmacology
pub_type： 杂志文章
doi：10.1111/j.1476-5381.1987.tb16827.x
更新日期：1987-01-01 00:00:00
abstract：:1. In this study we examined the effects of cortistatin, a putative endogenous ligand for somatostatin (SRIF) receptors, on the membrane properties of rat locus coeruleus (LC) neurones in vitro, by use of intracellular and whole cell patch clamp recording. We have compared the actions of cortistatin with those of SRIF...
journal_title：British journal of pharmacology
pub_type： 杂志文章
doi：10.1038/sj.bjp.0701541
更新日期：1997-12-01 00:00:00
