Abstract：
BACKGROUND AND PURPOSE:ARL 67156, 6-N,N-Diethyl-D-beta-gamma-dibromomethylene adenosine triphosphate, originally named FPL 67156, is the only commercially available inhibitor of ecto-ATPases. Since the first report on this molecule, various ectonucleotidases responsible for the hydrolysis of ATP at the cell surface have been cloned and characterized. In this work, we identified the ectonucleotidases inhibited by ARL 67156. EXPERIMENTAL APPROACH:The effect of ARL 67156 on recombinant NTPDase1, 2, 3 & 8 (mouse and human), NPP1, NPP3 and ecto-5'-nucleotidase (human) have been evaluated. The inhibition of the activity of NTPDases (using the following substrates: ATP, ADP, UTP), NPPs (pnp-TMP, Ap(3)A) and ecto-5'-nucleotidase (AMP) was measured by colorimetric or HPLC assays. KEY RESULTS:ARL 67156 was a weak competitive inhibitor of human NTPDase1, NTPDase3 and NPP1 with K(i) of 11+/-3, 18+/-4 and 12+/-3 microM, respectively. At concentrations used in the literature (50-100 microM), ARL 67156 partially but significantly inhibited the mouse and human forms of these enzymes. NTPDase2, NTPDase8, NPP3 and ecto-5'-nucleotidase activities were less affected. Importantly, ARL 67156 was not hydrolysed by either human NTPDase1, 2, 3, 8, NPP1 or NPP3. CONCLUSIONS AND IMPLICATIONS:In cell environments where NTPDase1, NTPDase3, NPP1 or mouse NTPDase8 are present, ARL 67156 would prolong the effect of endogenously released ATP on P2 receptors. However, it does not block any ectonucleotidases efficiently when high concentrations of substrates are present, such as in biochemical, pharmacological or P2X(7) assays. In addition, ARL 67156 is not an effective inhibitor of NTPDase2, human NTPDase8, NPP3 and ecto-5'-nucleotidase.
journal_name
Br J Pharmacoljournal_title
British journal of pharmacologyauthors
Lévesque SA,Lavoie EG,Lecka J,Bigonnesse F,Sévigny Jdoi
10.1038/sj.bjp.0707361subject
Has Abstractpub_date
2007-09-01 00:00:00pages
141-50issue
1eissn
0007-1188issn
1476-5381pii
0707361journal_volume
152pub_type
杂志文章abstract：:1. The effects of a number of Ca2+ channel blockers on the transmural electrical stimulation or receptor agonist-elicited contractile responses of guinea-pig ileum were compared. 2. omega-Conotoxins (MVIIA, GVIA, SVIB and MVIIC), but not omega-agatoxin IVA, completely blocked the twitch responses evoked by low frequen...
journal_title：British journal of pharmacology
pub_type： 杂志文章
doi：10.1111/j.1476-5381.1996.tb15470.x
更新日期：1996-06-01 00:00:00
abstract：:1. The potassium current in embryo spinal neurones of Xenopus consists of at least two kinetically distinct components with overlapping voltage-dependencies of activation. We investigated whether capsaicin might specifically block these components in acutely dissociated neurones from stage 37/38 embryos by use of stan...
journal_title：British journal of pharmacology
pub_type： 杂志文章
doi：10.1111/j.1476-5381.1996.tb15680.x
更新日期：1996-09-01 00:00:00
abstract：:The relative potencies of a series of substance P analogues have been determined for spasmogenic activity in the guinea-pig ileum in vitro and for the release of 86Rb and alpha-amylase activity from rat parotid gland slices in vitro. Equipotent molar ratios (EMR), relative to substance P, were determined for all the c...
journal_title：British journal of pharmacology
pub_type： 杂志文章
doi：10.1111/j.1476-5381.1982.tb08792.x
更新日期：1982-02-01 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：BACKGROUND AND PURPOSE:Diabetes is a risk factor for the development of coronary artery disease but it is not known whether the functions of endothelium-derived nitric oxide (NO) and endothelium-derived hyperpolarizing factor (EDHF) in coronary arteries are altered in the early stage of diabetes. Such alterations and t...
journal_title：British journal of pharmacology
pub_type： 杂志文章
doi：10.1111/j.1476-5381.2009.00348.x
更新日期：2009-09-01 00:00:00
abstract：:1. The inflammatory response induced by poly-L-arginine in the rat hind-paw was studied both by measuring paw oedema and histologically. 2. The paw volume was measured with a hydroplethysmometer at 0.5, 1, 2, 4, 6 and 18 h after the subplantar injection of the polycation. Protein extravasation was evaluated with Evans...
journal_title：British journal of pharmacology
pub_type： 杂志文章
doi：10.1111/j.1476-5381.1990.tb14193.x
更新日期：1990-12-01 00:00:00
abstract：BACKGROUND AND PURPOSE:Mitochondria possess their own source of cAMP, that is, soluble adenylyl cyclase (sAC). Activation or expression of mitochondrial sAC promotes mitochondrial function. Oestrogen receptor signalling plays an essential role in the regulation of mitochondrial function. Here we aimed to determine whet...
journal_title：British journal of pharmacology
pub_type： 杂志文章
doi：10.1111/bph.14455
更新日期：2018-10-01 00:00:00
abstract：:1. Intrasplenic injection of bradykinin (BK) induced a dose-dependent pressor response in the anaesthetized cat, with an ED50 of 0.98 +/- 0.43 nmol. In contrast, intrasplenic administration of desArg9bradykinin (desArg9BK) was without significant effect at doses of up to 200 nmol. 2. Intravenously administered BK indu...
journal_title：British journal of pharmacology
pub_type： 杂志文章
doi：10.1111/j.1476-5381.1993.tb13962.x
更新日期：1993-12-01 00:00:00
abstract：:Since its discovery over 50 years ago, cAMP has been the archetypal second messenger introducing students to the concept of cell signalling at the simplest level. As explored in this review, however, there are many more facets to cAMP signalling than the path from Gs-coupled receptor to adenylyl cyclase (AC) to cAMP t...
journal_title：British journal of pharmacology
pub_type： 杂志文章,评审
doi：10.1111/j.1476-5381.2011.01719.x
更新日期：2012-05-01 00:00:00
abstract：BACKGROUND AND PURPOSE:Atherosclerosis is associated with reduced vascular hydrogen sulfide (H2 S) biosynthesis. GYY4137 is a novel slow-releasing H2 S compound that may effectively mimic the time course of H2 S release in vivo. However, it is not known whether GYY4137 affects atherosclerosis. EXPERIMENTAL APPROACH:RA...
journal_title：British journal of pharmacology
pub_type： 杂志文章
doi：10.1111/bph.12246
更新日期：2013-08-01 00:00:00
abstract：:Oxidized ATP (oATP) is a Schiff-base-forming reagent that has been used for some years as an antagonist at the P2X7 receptor (P2X7R). Preincubation of mononuclear phagocytes with this inhibitor leads to attenuation of several proinflammatory responses triggered by extracellular ATP as well as a few non-nucleotide agon...
journal_title：British journal of pharmacology
pub_type： 评论,杂志文章,评审
doi：10.1038/sj.bjp.0705469
更新日期：2003-10-01 00:00:00
abstract：:Endothelin-1 (ET-1) is a peptide hormone produced within the myocardium which may modulate myocardial contractility in a paracrine-autocrine fashion. In the majority of species, ET-1 has a direct positive inotropic effect on the myocardium that involves both increased myofilament Ca(2+) sensitivity and increased Ca(2+...
journal_title：British journal of pharmacology
pub_type： 评论,杂志文章
doi：10.1038/sj.bjp.0707438
更新日期：2007-10-01 00:00:00
abstract：:1 The role of histamine H1- and H2-receptors in mediating the cutaneous inflammatory response produced by exogenous histamine and the release of endogenous histamine from mast cells has been investigated by a method which permits simultaneous, quantitative measurement of vasodilatation, vascular permeability and oedem...
journal_title：British journal of pharmacology
pub_type： 杂志文章
doi：10.1111/j.1476-5381.1980.tb07912.x
更新日期：1980-08-01 00:00:00
abstract：:1. A pentobarbitone-anaesthetized canine model of myocardial conduction was developed to evaluate drug effects on intra-atrial (I-A), intra-ventricular (I-V) and atrioventricular (A-V) conduction parameters, both at rest and during electrical pacing of the right atrium or ventricle. Drug effects on the ability of the ...
journal_title：British journal of pharmacology
pub_type： 杂志文章
doi：10.1111/j.1476-5381.1988.tb11444.x
更新日期：1988-02-01 00:00:00
abstract：:1. The concentrations of 5-hydroxytryptamine (5-HT), 5-hydroxyindolacetic acid (5-HIAA) and noradrenaline (NA) in homogenized rat brains were determined after intraperitoneal injection of 1,2,3,4-tetrahydro-2-naphthylamine (THN).2. THN caused a decrease in the concentration of brain 5-HIAA without altering its 5-HT co...
journal_title：British journal of pharmacology
pub_type： 杂志文章
doi：10.1111/j.1476-5381.1971.tb07109.x
更新日期：1971-06-01 00:00:00
abstract：:1 alpha-Flupenthixol (alpha-FPT; 0.2 mg/kg i.p.) when administered to rats produced catalepsy. 2 Baclofen (10 mg/kg i.p.) given 30 min after alpha-FPT had a biphasic effect on the catalepsy. Initially there was a potentiation of the effect, followed by a significant attenuation of the degree of catalepsy. 3 Possible m...
journal_title：British journal of pharmacology
pub_type： 杂志文章
doi：10.1111/j.1476-5381.1978.tb08460.x
更新日期：1978-02-01 00:00:00
abstract：BACKGROUND AND PURPOSE:3,4-Methylenedioxymethamphetamine (MDMA or 'Ecstasy') is a worldwide major drug of abuse known to elicit neurotoxic effects. The mechanisms underlying the neurotoxic effects of MDMA are not clear at present, but the metabolism of dopamine and 5-HT by monoamine oxidase (MAO), as well as the hepati...
journal_title：British journal of pharmacology
pub_type： 杂志文章
doi：10.1111/j.1476-5381.2011.01453.x
更新日期：2012-02-01 00:00:00
abstract：:1 The influence of the external calcium concentration on the effect of harmine 2 x 10(-5) M upon the guinea-pig atrial muscle was analysed. Transmembrane potentials of contractile fibres were measured during exposure to the drug at 30 degrees C. 2 In preparations superfused with 1.35 mM Ca2+-Tyrode solution and driven...
journal_title：British journal of pharmacology
pub_type： 杂志文章
doi：10.1111/j.1476-5381.1981.tb09986.x
更新日期：1981-10-01 00:00:00
abstract：:1. Porcine neuromedin U-8 produced a concentration (0.3 nM-1 microM)-dependent contraction of the longitudinal muscle of the human isolated ileum, which was unaffected by either atropine (1 microM) or tetrodotoxin (1 microM). 2. By contrast, neuromedin U-8 had only a weak effect on the circular muscle of the human iso...
journal_title：British journal of pharmacology
pub_type： 杂志文章
doi：10.1111/j.1476-5381.1990.tb14675.x
更新日期：1990-01-01 00:00:00
abstract：:Amyotrophic lateral sclerosis (ALS) is the most common motor neuron neurodegenerative disease. Although it has been classically considered as a disease limited to the motor system, there is increasing evidence for the involvement of other neural and non-neuronal systems. In this review, we will discuss currently exist...
journal_title：British journal of pharmacology
pub_type： 杂志文章,评审
doi：10.1111/bph.15202
更新日期：2020-07-16 00:00:00
abstract：:1 The effect of potassium channel opening compounds has been investigated in the smooth muscle of rabbit aorta under Ca-free conditions. Examination of the characteristics of the response has been performed using cromakalim as the prototype compound. 2 In order of potency, Ro 31-6930, cromakalim, minoxidil sulphate an...
journal_title：British journal of pharmacology
pub_type： 杂志文章
doi：10.1111/j.1476-5381.1992.tb13428.x
更新日期：1992-12-01 00:00:00
abstract：:1. Therapeutic doses of colistin sulphomethate sodium B.P. (Colomycin), pento-N sulphomethylpolymyxin B sodium (Thiosporin) and ampicillin B.P. (Penbritin) as well as normal saline have been given to volunteers with normal kidney function.2. A blind crossover technique was used and the effects of the compounds on bloo...
journal_title：British journal of pharmacology
pub_type： 临床试验,杂志文章,随机对照试验
doi：10.1111/j.1476-5381.1969.tb09545.x
更新日期：1969-09-01 00:00:00
abstract：:1. Under normal experimental conditions, the rabbit isolated distal saphenous artery appears to contain a homogeneous population of postjunctional alpha 1-adrenoceptors. Prazosin competitively antagonized responses to noradrenaline (NA) with a pA2 value of 8.6, while a relatively high concentration of rauwolscine (1 m...
journal_title：British journal of pharmacology
pub_type： 杂志文章
doi：10.1111/j.1476-5381.1991.tb09815.x
更新日期：1991-06-01 00:00:00
abstract：BACKGROUND AND PURPOSE:The effect of age on the distribution of morphine and morphine-3-glucuronide (M3G) across the blood-brain barrier (BBB) was studied in a sheep model utilizing intracerebral microdialysis. The effect of neonatal asphyxia on brain drug distribution was also studied. EXPERIMENTAL APPROACH:Microdial...
journal_title：British journal of pharmacology
pub_type： 杂志文章
doi：10.1111/j.1476-5381.2009.00242.x
更新日期：2009-07-01 00:00:00
abstract：:The effects of the angiotensin-converting-enzyme inhibitor (ACEI) ramiprilat, the angiotensin II type 1 receptor antagonist (AT(1)A) candesartan, and the combination of both drugs on infarct size (IS) resulting from regional myocardial ischaemia were studied in pigs. Both ACEI and AT(1)A reduce myocardial IS by a brad...
journal_title：British journal of pharmacology
pub_type： 杂志文章
doi：10.1038/sj.bjp.0703544
更新日期：2000-09-01 00:00:00
abstract：:Chemotherapy-induced immune-suppression is a common, but potential detrimental, adverse reaction in patients undergoing treatment for cancer and strategies with capacity to boost the immune cell populations are needed. Physical exercise training is a potent regulator of immune cell viability and function and may serve...
journal_title：British journal of pharmacology
pub_type： 杂志文章,评审
doi：10.1111/bph.15141
更新日期：2020-05-25 00:00:00
abstract：:1. The interactive effects of different metabotropic glutamate (mGlu) receptor subtypes to regulate phosphoinositide turnover have been studied in neonatal rat cerebral cortex and hippocampus by use of agonists and antagonists selective between group I and II mGlu receptors. 2, The group II-selective agonist 2R,4R-4-a...
journal_title：British journal of pharmacology
pub_type： 杂志文章
doi：10.1038/sj.bjp.0701626
更新日期：1998-02-01 00:00:00
abstract：:1 Amodiaquine was found to be a potent inhibitor in vitro of gastric histamine methyltransferase from human and canine corpus and from pig antrum. The ID50 for the enzyme, purified from pig antrum mucosa by ultracentrifugation and chromatography on DEAE-cellulose, was 2.5 muM. 2 In six dogs with Heidenhanin pouches th...
journal_title：British journal of pharmacology
pub_type： 杂志文章
doi：10.1111/j.1476-5381.1975.tb06934.x
更新日期：1975-11-01 00:00:00
abstract：BACKGROUND AND PURPOSE:Inhalation of the superantigen,staphylococcal enterotoxin B (SEB), leads to the activation of the host T and invariant natural killer (iNK) T cells, thereby resulting in acute lung inflammation and respiratory failure but the underlying mechanism(s) of disease remain elusive, with limited treatme...
journal_title：British journal of pharmacology
pub_type： 杂志文章
doi：10.1111/j.1476-5381.2012.02063.x
更新日期：2012-11-01 00:00:00
abstract：:The concentrations of catecholamines and the activities of dopamine-beta-hydroxylase were measured in blood obtained from decapitated diabetic and aged-matched control rats. The activity of dopamine-beta-hydroxylase in blood from diabetic rats was much greater (5 fold) than that seen for control rats. For both diabeti...
journal_title：British journal of pharmacology
pub_type： 杂志文章
doi：10.1111/j.1476-5381.1978.tb08632.x
更新日期：1978-09-01 00:00:00
