Abstract:
:Natural purines like ATP, ADP and adenosine have crucial roles in platelet physiology. This knowledge has been significant in drug development and today ADP receptor antagonists are widely used for prevention of thrombotic events following myocardial infarction and ischaemic stroke. Recent studies have shown that a purine analogue bearing nitrate ester group (denoted MK128) has anti-inflammatory effects probably due to its ability to donate nitric oxide (NO). However, other pharmacological mechanisms may contribute to the observed effect. The aim of the present study was to establish the anti-platelet activity and elucidate the underlying molecular mechanism(s) of the purine analogue MK128. We found that MK128 reduced aggregation and secretion induced by the thrombin receptor agonist SFLLRN and nearly abolished aggregation and secretion induced by thromboxane A2 (TxA2) and collagen receptor agonists. The inhibition took place despite blockage of the NO/cGMP signalling system. Furthermore, interaction between MK128 and platelet purinergic receptors did not explain the observed inhibition. Instead, we found that MK128 concentration-dependently inhibited Rho-associated kinase (ROCK), which led to decreased ROCK-dependent myosin phosphatase target subunit (MYPT)-1 phosphorylation and suppression of platelet functional responses.
journal_name
Eur J Pharmacoljournal_title
European journal of pharmacologyauthors
Kardeby C,Paramel GV,Pournara D,Fotopoulou T,Sirsjö A,Koufaki M,Fransén K,Grenegård Mdoi
10.1016/j.ejphar.2019.172428subject
Has Abstractpub_date
2019-08-15 00:00:00pages
172428eissn
0014-2999issn
1879-0712pii
S0014-2999(19)30379-6journal_volume
857pub_type
杂志文章abstract::The effects of bepridil and nifedipine, newly developed Ca2+ antagonists, were studied on the spontaneous action potentials of the true pacemaker cell preparations (0.5 X 0.5 mm) obtained from the rabbit sino-atrial (SA) node. At the lower concentrations, bepridil (10(-6) M) and nifedipine (10(-8) M) decreased the spo...
journal_title:European journal of pharmacology
pub_type: 杂志文章
doi:10.1016/0014-2999(84)90245-0
更新日期:1984-03-23 00:00:00
abstract::Hyperphosphatemia is associated with severe decline of renal function in chronic kidney disease and elevates cardiovascular mortality. Type II sodium dependent phosphate transporter 2A (Npt2A) plays a major role in renal phosphate reabsorption and could be explored as a target for anti-hyperphosphatemia therapy. Human...
journal_title:European journal of pharmacology
pub_type: 杂志文章
doi:10.1016/j.ejphar.2013.09.005
更新日期:2013-12-05 00:00:00
abstract::The objective of this study was to determine the in vivo effectiveness of the selective endothelin ETA receptor antagonist PD 156707 (sodium 2-benzo[1,3]dioxol-5-yl-4-(4-methoxy-phenyl)-4-oxo-3-(3,4,5-trimet hoxy- benzyl)-but-2-enoate). Effectiveness was defined by the ability of the compound to block increases in ren...
journal_title:European journal of pharmacology
pub_type: 杂志文章
doi:10.1016/s0014-2999(96)00954-5
更新日期:1997-03-05 00:00:00
abstract::(-)Baclofen, a GABAB receptor agonist, and GABA attenuated by 60% the high K+-evoked 45Ca2+ uptake into cultured cerebellar granule cells with an EC50 of 110 +/- 18 nM and 2.4 +/- 0.2 microM, respectively. The attenuation by baclofen of 45Ca2+ uptake was stereospecific and the effect of GABA was unaffected by bicucull...
journal_title:European journal of pharmacology
pub_type: 杂志文章
doi:10.1016/0014-2999(87)90557-7
更新日期:1987-09-23 00:00:00
abstract::The effects of almitrine on the contractile properties of isolated geniohyoid and sternohyoid muscles were determined in physiological salt solution at 30 degrees C in young and old rats. In young rats, almitrine had no effect on twitch or tetanic tension, twitch:tetanic tension ratio, contractile kinetics, active or ...
journal_title:European journal of pharmacology
pub_type: 杂志文章
doi:10.1016/s0014-2999(01)00721-x
更新日期:2001-01-26 00:00:00
abstract::We investigated in vitro anti-inflammatory effects of cynaropicrin, a sesquiterpene lactone from Saussurea lappa, on tumor necrosis factor (TNF)-alpha and nitric oxide (NO) release, and lymphocyte proliferation. Cynaropicrin strongly inhibited TNF-alpha release from lipopolysaccharide-stimulated murine macrophage, RAW...
journal_title:European journal of pharmacology
pub_type: 杂志文章
doi:10.1016/s0014-2999(00)00337-x
更新日期:2000-06-23 00:00:00
abstract::Cultured chick hepatocytes were used to investigate the hepatotoxicity of methotrexate alone and in combination with paracetamol. Treatment with methotrexate alone at concentrations as high as 1 mg/ml resulted in no toxicity in cultured chick hepatocytes, as indicated by no detachment of cells and no effect on protein...
journal_title:European journal of pharmacology
pub_type: 杂志文章
doi:10.1016/0926-6917(93)90063-v
更新日期:1993-04-01 00:00:00
abstract::Certain neuropeptides, including vasoactive intestinal peptide, inhibit peptidoleukotriene release from platelet activating factor-stimulated rat lung. We have now shown that vasoactive intestinal peptide will also inhibit peptidoleukotriene release from platelet activating factor-stimulated or ovalbumin-challenged gu...
journal_title:European journal of pharmacology
pub_type: 杂志文章
doi:10.1016/0014-2999(89)90610-9
更新日期:1989-03-14 00:00:00
abstract::The tension in isolated ring preparations of the thoracic aorta from Wistar-Kyoto rats (WKY) and spontaneously hypertensive rats (SHR) was measured isometrically to study if there are any differences in the mechanisms of 17beta-estradiol- or progesterone-induced relaxation between WKY and SHR aortic rings. 17beta-Estr...
journal_title:European journal of pharmacology
pub_type: 杂志文章
doi:10.1016/s0014-2999(03)01858-2
更新日期:2003-07-04 00:00:00
abstract::We investigated the effects of KF19514 (5-phenyl-3-(3-pyridyl)methyl-3H-imidazo[4,5-c][1,8]naphthyridin-4 (5H)-one) on bronchoconstriction and allergic inflammation in guinea pigs and on tumor necrosis factor-alpha production in mice. KF19514 inhibited phosphodiesterase 4 (IC50 = 0.40 microM) and phosphodiesterase 1 (...
journal_title:European journal of pharmacology
pub_type: 杂志文章
doi:10.1016/s0014-2999(97)01063-7
更新日期:1997-07-30 00:00:00
abstract::Osthole is a coumarin extracted from Cnidium monnieri (L.) Cusson. The medicinal plant is widely used in Vietnamese as well as Chinese traditional medicine as a vasodilating and antihypertensive agent. Here we have tested the proposition that the block of Ca(v)1.2 channels is mainly responsible for its vascular activi...
journal_title:European journal of pharmacology
pub_type: 杂志文章
doi:10.1016/j.ejphar.2012.01.038
更新日期:2012-04-05 00:00:00
abstract::The sulfonylurea compounds glisoxepide and glibenclamide inhibit the uptake of bile acids into isolated rat hepatocytes. The Ki values for the inhibition of cholate uptake was 9 microM with glibenclamide and 200 microM with glisoxepide. The inhibition of cholate uptake by both sulfonylureas was noncompetitive. Uptake ...
journal_title:European journal of pharmacology
pub_type: 杂志文章
doi:10.1016/0014-2999(92)90628-h
更新日期:1992-03-31 00:00:00
abstract::In the present work we evaluated the anticonvulsant effects of two novel antagonists of the glycine co-agonist site (glycineB receptor) within the N-methyl-D-aspartate (NMDA) receptor complex, MRZ 2/576 (a tricyclic pyrido-phtalazin dione derivative) and L-701,324 (7-chloro-4-hydroxy-3-(3-phenoxy)phenyl-2(H)quinoline)...
journal_title:European journal of pharmacology
pub_type: 杂志文章
doi:10.1016/s0014-2999(97)01452-0
更新日期:1998-01-19 00:00:00
abstract::The release of [3H]5-hydroxytryptamine ([3H]5-HT) evoked by 15 mM KCl in superfused rat cerebellum synaptosomes was inhibited by 5-HT (pEC30 = 8.73). Methiothepin antagonized 5-HT (pA2 = 9.28); ketanserin, methysergide, cinanserin and spiperone were ineffective. The receptors involved were activated (pEC30 = 8.90) by ...
journal_title:European journal of pharmacology
pub_type: 杂志文章
doi:10.1016/0014-2999(86)90065-8
更新日期:1986-07-31 00:00:00
abstract::The effect of cannabinoid receptor activation and blockade on the propulsive activity in the mouse small intestine was assessed in the present study by measuring the transit of an orally administered, non-absorbable marker. The cannabinoid receptor agonist WIN 55,212-2 (R(+)-[2,3-dihydro-5-methyl-3[(morpholinyl)methyl...
journal_title:European journal of pharmacology
pub_type: 杂志文章
doi:10.1016/s0014-2999(97)01555-0
更新日期:1998-02-26 00:00:00
abstract::Human neuroblastoma SH-SY5Y cells express endogenous mu-opioid receptor and develop cellular tolerance to morphine after prolonged (>/=4 h) treatment with morphine. Treatment with forskolin (25 microM, 12 h), an adenylyl cyclase activator, also desensitized mu-opioid receptor response to morphine (10 microM) by 38% (P...
journal_title:European journal of pharmacology
pub_type: 杂志文章
doi:10.1016/s0014-2999(99)00881-x
更新日期:2000-02-18 00:00:00
abstract::The inhibition by various serotonin agonists and antagonists of the binding of 3 nM 3H-d-LSD, 1.7 nM 3H-serotonin and 0.22 nM 3H-spiperone to homogenates of calf hippocampus and frontal cortex was studied. The 50% inhibitory concentration (IC50) for these drugs versus 3H-d-LSD binding had similar values to and correla...
journal_title:European journal of pharmacology
pub_type: 杂志文章
doi:10.1016/0014-2999(80)90141-7
更新日期:1980-08-29 00:00:00
abstract::The suppression of pro-inflammatory cytokine-induced inflammation responses is an attractive pharmacological target for the development of therapeutic strategies for inflammatory bowel disease (IBD). In the present study, we evaluated the anti-inflammatory properties of flavonoid isoliquiritigenin (ISL) in intestinal ...
journal_title:European journal of pharmacology
pub_type: 杂志文章
doi:10.1016/j.ejphar.2016.12.026
更新日期:2017-02-05 00:00:00
abstract::The aim of the present study was to examine the influence of ifenprodil (a non-competitive NMDA receptor antagonist which also blocks 5-HT3 receptors and alpha1-adrenoceptors) on the effects of ethanol in the mouse in vivo and to elucidate the role of various receptors in these actions. The ethanol (4 g/kg i.p.)-induc...
journal_title:European journal of pharmacology
pub_type: 杂志文章
doi:10.1016/s0014-2999(99)00393-3
更新日期:1999-07-14 00:00:00
abstract::The relationship between adipocytes and infiltrated macrophages in fat tissue is important for the pathogenesis of insulin resistance through the activation of cytokines. Peroxisome proliferator-activated receptors (PPARs) play a role in the regulation of cytokine secretion in these cells. We studied the effect of the...
journal_title:European journal of pharmacology
pub_type: 杂志文章
doi:10.1016/j.ejphar.2006.12.037
更新日期:2007-04-30 00:00:00
abstract::The bronchial smooth muscle of the rat was examined for contractile responses to excitatory amino acids. The nerve-mediated contraction induced by electrical field stimulation was enhanced by exogenous L-glutamate (L-Glu). The apparent affinity (ED50) of L-Glu was 3.5 +/- 0.1 mM. Both tetrodotoxin and hemicholinium-3 ...
journal_title:European journal of pharmacology
pub_type: 杂志文章
doi:10.1016/0014-2999(89)90235-5
更新日期:1989-05-02 00:00:00
abstract::The present study was undertaken to investigate the effects of intracavernosal injections of adrenomedullin, a novel hypotensive peptide, on penile erection in anesthetized cats. Responses to adrenomedullin were compared to those elicited by intracavernosal injection of the control triple-drug combination (1.65 mg pap...
journal_title:European journal of pharmacology
pub_type: 杂志文章
doi:10.1016/s0014-2999(96)00924-7
更新日期:1997-01-14 00:00:00
abstract::Histamine induced a dose-dependent stimulation of 3H-catecholamine(CA) efflux (superfusion procedure) from hypothalamic, striatal, hippocampal and cortical slices. The extra-hypothalamic regions were the most sensitive to histamine. Efflux of 14C-GABA and 14C-(acetyl)choline was not affected. The effect of histamine o...
journal_title:European journal of pharmacology
pub_type: 杂志文章
doi:10.1016/0014-2999(77)90126-1
更新日期:1977-05-15 00:00:00
abstract::Glucocorticoids can reverse hemodynamic disturbances and dependence on catecholamines in septic shock. The relevant beneficial mechanisms of steroids in septic shock are unknown, although inducible nitric oxide synthase could account for them. The aim of this study was to compare the effects of dexamethasone, a glucoc...
journal_title:European journal of pharmacology
pub_type: 杂志文章
doi:10.1016/s0014-2999(03)02035-1
更新日期:2003-08-15 00:00:00
abstract::Urinary obstruction from benign prostatic hyperplasia is a common clinical problem possibly associated with excessive prostatic constriction around the urethra. These studies compared adrenergic and serotonergic functional activity to specific alpha 1 and serotonin (5-hydroxytryptamine; 5-HT) binding sites in the rat ...
journal_title:European journal of pharmacology
pub_type: 杂志文章
doi:10.1016/0014-2999(94)00613-c
更新日期:1995-01-24 00:00:00
abstract::The ligand preferences of recombinant NR1 homomeric and NR1-NR2 heteromeric NMDA receptors were examined by homogenate binding assay. The binding affinities for most ligands were similar to those reported for native NMDA receptors. The order of affinity for [3H]glutamate was NR1-NR2B > NR1-NR2A approximately NR1-NR2D ...
journal_title:European journal of pharmacology
pub_type: 杂志文章
doi:10.1016/0922-4106(94)90058-2
更新日期:1994-08-16 00:00:00
abstract::A bicarbonate-dependent organic cation transporter, unique from rOCT1 and rOCT2, primarily mediates amantadine uptake into renal proximal tubules. We examined whether intracellular pH regulates bicarbonate-dependent amantadine transporter function in these tubules. NH(4)Cl treatment resulted in immediate intracellular...
journal_title:European journal of pharmacology
pub_type: 杂志文章
doi:10.1016/j.ejphar.2006.04.051
更新日期:2006-07-10 00:00:00
abstract::ICI 169,369 is a chemically novel 5-HT antagonist that has higher affinity for the 5-HT2 binding sites in rat cortex than it has for 5-HT1 sites (Ki 1.79 x 10(-8) and 1.58 x 10(-6) M, respectively). In isolated tissue preparations ICI 169,369 was shown to be a competitive antagonist of 5-HT on the rabbit aorta, pig co...
journal_title:European journal of pharmacology
pub_type: 杂志文章
doi:10.1016/0014-2999(88)90005-2
更新日期:1988-06-10 00:00:00
abstract::Endogenous hydrogen sulfide is produced by cystathionine-γ-lyase and cystathionine-β-synthase in a variety of tissues and has recently been implicated in the regulation of cardiac functions. Acceleration of the heart rate in response to catecholamines is impaired in patients with cirrhosis. The present study was aimed...
journal_title:European journal of pharmacology
pub_type: 杂志文章
doi:10.1016/j.ejphar.2012.09.039
更新日期:2012-12-05 00:00:00
abstract::The alpha 1-adrenoceptor agonist, SDZ NVI-085 ((-)-(4aR,10aR)-3,4,4a,5,10,10a-hexahydro-6-methoxy-4- methyl-9-(methylthio)-2H-naphth[2,3-b]-1,4-oxazine.HCl; 1 mg/kg i.p.), decreased body temperature of guinea-pigs. Two 5-HT1D receptor antagonists, GR127935 (N-[4-methoxy-3-(4-methyl-1-piperazinyl)phenyl]-2'-methyl-4'-(...
journal_title:European journal of pharmacology
pub_type: 杂志文章
doi:10.1016/0014-2999(95)00526-q
更新日期:1995-10-24 00:00:00