Abstract：
:Molecules regulating cell death constitute prominent therapeutic targets. The pro-apoptotic role of serine protease inhibitors prompted us to search for novel modulators of this process. We have tested some recently synthesized antithrombotic compounds for their potential to induce apoptotic cell death. Cell based analyses revealed that inhibitors built on the azaphenylalanine scaffold are, for B-cell lymphoma cells, severely cytotoxic, while other compounds tested were moderate or non-cytotoxic. These inhibitors induced the time and concentration dependent biochemical and morphological characteristics of apoptosis, such as DEVDase activation, loss of mitochondrial membrane potential, nuclear degradation and genomic DNA fragmentation. Most of the inhibitors proved to be selective for thrombin, with inhibition constants (K(i)) in the nanomolar range. However, they could also inhibit at least one additional serine protease (trypsin, chymotrypsin and/or coagulation factor X) with K(i) values in the nanomolar or low micromolar range. These serine protease inhibitors constitute novel apoptosis inducing compounds in B-cell lymphoma cells.
journal_name
Eur J Pharmacoljournal_title
European journal of pharmacologyauthors
Celhar T,Batista Napotnik T,Obreza A,Zega A,Anderluh PS,Kikelj D,Mlinaric-Rascan Idoi
10.1016/j.ejphar.2008.11.008subject
Has Abstractpub_date
2009-01-05 00:00:00pages
15-22issue
1eissn
0014-2999issn
1879-0712pii
S0014-2999(08)01132-1journal_volume
602pub_type
杂志文章abstract：:Recent reports show that the nuclear factor-κB (NF-κB) can control numerous genes encoding inflammatory and nociceptive mediators and play an important role in the development of central pain sensitization. The aim of the present study is to assess the role of NF-κB signal pathway and its downstream pro-inflammatory c...
journal_title：European journal of pharmacology
pub_type： 杂志文章
doi：10.1016/j.ejphar.2012.02.017
更新日期：2012-05-05 00:00:00
abstract：:The prefrontal cortex and the mediodorsal thalamic nucleus are reciprocally connected through excitatory amino acid pathways. Cortical excitatory responses resulting from activation of either the mediodorsal thalamic nucleus-prefrontal cortex pathway (short latency) or the recurrent collaterals of prefrontal cortex-me...
journal_title：European journal of pharmacology
pub_type： 杂志文章
doi：10.1016/0014-2999(95)00377-w
更新日期：1995-10-04 00:00:00
abstract：:Acid-sensing ion channels (ASICs) are involved in numerous physiological and pathological processes in the central nervous system. Development of pharmacological tools capable to inhibit or potentiate these channels is important for our knowledge about roles of ASICs in the neuronal network and can be promising for tr...
journal_title：European journal of pharmacology
pub_type： 杂志文章
doi：10.1016/j.ejphar.2016.06.013
更新日期：2016-10-05 00:00:00
abstract：:Acute (-)-nicotine administration (0.4 and 0.8 mg/kg s.c.) produced a regionally specific increase in the rate of catecholamine synthesis in the rat nucleus accumbens, hypothalamus and hippocampus but not elsewhere, including the caudate-putamen. In all regions rates of 5-hydroxytryptamine synthesis were unaffected. (...
journal_title：European journal of pharmacology
pub_type： 杂志文章
doi：10.1016/0014-2999(89)90440-8
更新日期：1989-08-29 00:00:00
abstract：:The G protein-coupled receptor Mas is a physiological antagonist of the angiotensin II type 1 receptor and is associated with angiotensin-(1-7) signaling. We investigated the effect of Mas-deficiency on blood pressure regulation under physiological conditions and salt load using radiotelemetry. Mas-knockout mice and t...
journal_title：European journal of pharmacology
pub_type： 杂志文章
doi：10.1016/j.ejphar.2012.05.025
更新日期：2012-08-15 00:00:00
abstract：:Alzheimer's disease, an age-related neurodegenerative disorder, is characterized clinically by a progressive loss of memory and cognitive functions. Neuropathologically, Alzheimer's disease is defined by the accumulation of extracellular amyloid protein deposited senile plaques and intracellular neurofibrillary tangle...
journal_title：European journal of pharmacology
pub_type： 杂志文章,评审
doi：10.1016/j.ejphar.2006.06.026
更新日期：2006-09-01 00:00:00
abstract：:Sprague-Dawley rats received oral doses of enalapril maleate (5 mg/kg), a potent, nonsulfhydryl, angiotensin converting enzyme inhibitor, or saline. Sixty min later, morphine sulfate, 5 mg/kg, or saline was injected subcutaneously. Response to a thermal stimulus was monitored before and up to 5 h ter morphine injectio...
journal_title：European journal of pharmacology
pub_type： 杂志文章
doi：10.1016/0014-2999(84)90607-1
更新日期：1984-02-17 00:00:00
abstract：:As there are significant amounts of functional endothelin receptors in the mammalian urinary tract, we examined the effect of experimental diabetes on the expression of endothelin receptors and their mRNAs in the rat bladder dome. The density of endothelin receptors in the rat bladder dome was higher (8 and 16 weeks f...
journal_title：European journal of pharmacology
pub_type： 杂志文章
doi：10.1016/s0014-2999(99)00753-0
更新日期：2000-01-17 00:00:00
abstract：:Endogenous opioid and nociceptin systems are widely distributed in the gastrointestinal tract where they seem to play a crucial role in maintaining the intestinal homeostasis. The aim of our study was to assess whether activation of nociceptin (NOP) and µ-opioid (MOP) receptors by a mixed NOP/MOP receptor agonist, BU0...
journal_title：European journal of pharmacology
pub_type： 杂志文章
doi：10.1016/j.ejphar.2015.09.021
更新日期：2015-10-15 00:00:00
abstract：:The pharmacological mechanisms involved in the interactions between C-fibers, cholinergic fibers and mast cells were investigated in tracheally perfused rabbit lungs by measuring the simultaneous release of substance P and histamine in lung effluents. The amounts of substance P and histamine released in lung superfusa...
journal_title：European journal of pharmacology
pub_type： 杂志文章
doi：10.1016/s0014-2999(99)00176-4
更新日期：1999-04-23 00:00:00
abstract：:The role of the endogenous corticotropin-releasing hormone (CRH) system in the regulation of heart rate, PQ interval (a measure of vagal activity), gross activity and release of adrenocorticotropic hormone (ACTH), noradrenaline and adrenaline into the blood during conditioned fear was studied in freely moving rats. In...
journal_title：European journal of pharmacology
pub_type： 杂志文章
doi：10.1016/s0014-2999(99)00870-5
更新日期：2000-02-11 00:00:00
abstract：:Chronic administration of amphetamine to cats (twice daily, in doses increasing from 5 to 15 mg/kg over a 10-day period) elicited a number of behaviors e.g., limb flicking, abortive grooming, and excessive head shaking, which were originally proposed as an animal behavioral model for studying the actions of hallucinog...
journal_title：European journal of pharmacology
pub_type： 杂志文章
doi：10.1016/0014-2999(84)90138-9
更新日期：1984-04-06 00:00:00
abstract：:We previously described two novel peptides, Ca2+-like peptide (CALP) 1 and CALP2, which interact with Ca2+-binding EF hand motifs, and therefore have the characteristics to define the role of the Ca2+-sensing regulatory protein calmodulin in asthma. In the present study, the effects of the calcium-like peptides were i...
journal_title：European journal of pharmacology
pub_type： 杂志文章
doi：10.1016/s0014-2999(03)02016-8
更新日期：2003-08-22 00:00:00
abstract：:We examined the effects of (+/-)-(E)-4-ethyl-2-[(E)-hydroxyimino]-5-nitro-3-hexenamide (FK409), a nitric oxide (NO) donor, on renal actions and norepinephrine overflow induced by renal nerve stimulation in anesthetized dogs, with or without N(G)-nitro-L-arginine (NOARG), a NO synthase inhibitor. Renal nerve stimulatio...
journal_title：European journal of pharmacology
pub_type： 杂志文章
doi：10.1016/s0014-2999(97)01424-6
更新日期：1998-01-12 00:00:00
abstract：:Our previous research showed that ATP and adenosine 5'-O-2-thiodiphosphate (ADPbetaS) induce contractile effects in the longitudinal muscle of mouse distal colon via activation of P2Y receptors which are not P2Y(1) or P2Y(12) subtypes. This study investigated the nature of the P2Y receptor subtype(s) and the mechanism...
journal_title：European journal of pharmacology
pub_type： 杂志文章
doi：10.1016/j.ejphar.2008.07.057
更新日期：2008-10-24 00:00:00
abstract：:The present study was performed to clarify the mechanism of change in intraocular pressure by 2-(1-hexyn-1-yl)adenosine (2-H-Ado), a selective adenosine A2 receptor agonist, in rabbits. 2-H-Ado (0.1%, 50 microl)-induced ocular hypertension (E(max): 7.7 mm Hg) was inhibited by an adenosine A2A receptor antagonist 1,3,7...
journal_title：European journal of pharmacology
pub_type： 杂志文章
doi：10.1016/j.ejphar.2005.03.002
更新日期：2005-08-22 00:00:00
abstract：:UP 269-6, 5-methyl-7-propyl-8(-)[2'-(1H-tetrazol-5-yl)biphenyl-4- yl)methyl]-1,2,4-triazolo]1,5-c]pyrimidin-2(3H)-one is a novel nonpeptide angiotensin II receptor antagonist. In vivo studies were performed to evaluate UP 269-6 for its angiotensin II antagonistic action. In pithed rats, i.v. administration of UP 269-6...
journal_title：European journal of pharmacology
pub_type： 杂志文章
doi：10.1016/0014-2999(95)00395-2
更新日期：1995-09-15 00:00:00
abstract：:In the guinea-pig ileum, both sarafotoxin S6c and IRL1620 (Suc-[Glu9,Ala11,15]endothelin-1-(8-21) induced a concentration-dependent biphasic effect (relaxation and contraction), but distinct tachyphylaxis of the tissue. Cross-tachyphylaxis and additivity experiments evidenced distinct receptors for these agonists. BQ-...
journal_title：European journal of pharmacology
pub_type： 杂志文章
doi：10.1016/s0014-2999(99)00062-x
更新日期：1999-03-19 00:00:00
abstract：:UL-FS 49, a chemical congener of AQ-A 39 with structural similarities to verapamil, decreased the rate of spontaneously beating guinea-pig atria at much lower concentrations (effective concentration 30%, EC30 = 0.030 microgram/ml) than it decreased the contractility (2.5 Hz; EC30 = 108 micrograms/ml) and maximal drivi...
journal_title：European journal of pharmacology
pub_type： 杂志文章
doi：10.1016/0014-2999(84)90363-7
更新日期：1984-09-03 00:00:00
abstract：:The pharmacological treatment of mood and anxiety disorders has for long relied on the serendipitous findings of monoaminergic and benzodiazepine drugs more than 50 years ago. These treatments, however, are therapeutically insufficient and even though more recently developed drugs are particularly improving side effec...
journal_title：European journal of pharmacology
pub_type： 杂志文章,评审
doi：10.1016/j.ejphar.2008.01.057
更新日期：2008-05-13 00:00:00
abstract：:Drugs belonging to different chemical classes having the ability to improve behavioral performance in animal learning and memory tests may share the common ability to stimulate protein kinase C activity in rat brain cortex. In vitro acetyl-L-carnitine (100 nM) promoted in rat brain cortex slices a significant increase...
journal_title：European journal of pharmacology
pub_type： 杂志文章
doi：10.1016/0014-2999(94)90216-x
更新日期：1994-11-14 00:00:00
abstract：:The antagonist potencies of SCH 23390 and domperidone have been determined at vascular and neuronal dopamine receptors in the rabbit isolated splenic artery and rectococcygeus muscle, respectively. SCH 23390 was a potent, competitive antagonist at vascular (pA2 = 10.65) but not neuronal (pA2 less than 6.0) receptors. ...
journal_title：European journal of pharmacology
pub_type： 杂志文章
doi：10.1016/0014-2999(85)90199-2
更新日期：1985-10-08 00:00:00
abstract：:Prulifloxacin, a new thiazeto-quinoline derivative with antibiotic properties, was evaluated for cardiac risk both in vitro on the ether-à-go-go-related gene (HERG) K+ channel, and in vivo in the conscious dog monitored by telemetry. HERG current was measured from stably transfected human embryonic kidney (HEK) 293 ce...
journal_title：European journal of pharmacology
pub_type： 杂志文章
doi：10.1016/s0014-2999(03)02180-0
更新日期：2003-09-05 00:00:00
abstract：:In this study, we synthesized a novel carbazole derivative, MHY407, as a sensitizer of cancer cells to increase DNA damage. We then evaluated the anticancer effects of MHY407 and identified the molecular mechanism for the sensitization of breast cancer cell lines. MHY407 significantly increased DNA damage as determine...
journal_title：European journal of pharmacology
pub_type： 杂志文章
doi：10.1016/j.ejphar.2012.10.001
更新日期：2012-12-15 00:00:00
abstract：:The intracerebroventricularly (i.c.v.) injected presynaptic alpha2-adrenoceptor agonists, clonidine and oxymetazoline, exerted a dose-dependent inhibition on the gastric acid secretion in pylorus-ligated rats; the ED50 values were 20 and 7.5 nmol/rat, respectively. Moreover, beta-endorphin, given i.c.v., also decrease...
journal_title：European journal of pharmacology
pub_type： 杂志文章
doi：10.1016/s0014-2999(01)01572-2
更新日期：2002-01-25 00:00:00
abstract：:In utero exposure of rodents to valproic acid (VPA) has been proposed to induce an adult phenotype with behavioural characteristics reminiscent of those observed in autism spectrum disorder (ASD). Our previous studies have demonstrated the social cognition deficits observed in this model, a major core symptom of ASD, ...
journal_title：European journal of pharmacology
pub_type： 杂志文章
doi：10.1016/j.ejphar.2014.01.050
更新日期：2014-03-15 00:00:00
abstract：:5-(2'-[18F]Fluoroethyl)flumazenil ([18F]FEF), a fluorine-18-labeled analogue of the benzodiazepine antagonist flumazenil, was evaluated for use with positron emission tomography (PET). PET imaging of a baboon after i.v. injection of [18F]FEF showed that the radiofluorinated ligand rapidly localized in vivo within benz...
journal_title：European journal of pharmacology
pub_type： 杂志文章
doi：10.1016/0014-2999(92)90153-u
更新日期：1992-07-21 00:00:00
abstract：:Transient ischemia was produced for 15 min by occlusion of the middle cerebral artery in halothane-anesthetized rats, and changes in the extracellular concentrations of neurotransmitter monoamines and amino acids were examined in the striatum. The occlusion produced marked increases in the extracellular concentrations...
journal_title：European journal of pharmacology
pub_type： 杂志文章
doi：10.1016/j.ejphar.2003.11.006
更新日期：2004-01-26 00:00:00
abstract：:Transient activation of the outward K+ current caused by a rise in the cytosolic free Ca2+ concentration, [Ca2+]i was the predominant change in plasma membrane ion flux during the first phase of thyrotropin-releasing hormone (TRH) action on pituitary cells. Following the intracellular application of inhibitors of 1,2-...
journal_title：European journal of pharmacology
pub_type： 杂志文章
doi：10.1016/0922-4106(89)90046-1
更新日期：1989-03-07 00:00:00
abstract：:An unbiased conditioned place preference paradigm was used to evaluate the effect of dextro-morphine on the morphine-produced reward in male CD rats. Morphine sulfate (1-10 mg/kg) given intraperitoneally dose-dependently produced the conditioned place preference. Pretreatment with dextro-morphine at a dose from 0.1 to...
journal_title：European journal of pharmacology
pub_type： 杂志文章
doi：10.1016/j.ejphar.2007.01.083
更新日期：2007-05-21 00:00:00
