Abstract：
:The efficacy of a novel, nonpeptidic, caspase 3/7-selective inhibitor, (S)-(+)-5-[1-(2-methoxymethylpyrrolidinyl)sulfonyl]isatin (MMPSI) for reducing ischemic injury in isolated rabbit hearts or cardiomyocytes was evaluated. MMPSI (0.1-10 microM) evoked a concentration-dependent reduction in infarct size (up to 56% vs. control; IC(50)=0.2 microM). Furthermore, apoptosis (DNA laddering, soluble nucleosomes) was reduced in the ischemic area-at-risk. MMPSI inhibited recombinant human caspase-3 with an IC(50)=1.7 microM. Apoptosis in H9c2 cells after 16-h simulated ischemia and 2-h simulated reperfusion was significantly reduced by MMPSI in a concentration-dependent manner (IC(50)=0.5 microM); similar effects were observed in isolated adult rabbit cardiomyocytes (IC(50)=1.5 microM). These data support an important role for caspase-3/7 in mediating myocardial ischemic injury. Furthermore, these data indicate that cardioprotection via caspase-3/7 inhibition is attainable via a small molecule (nonpeptidic) inhibitor, a necessary step in making this approach therapeutically viable.
journal_name
Eur J Pharmacoljournal_title
European journal of pharmacologyauthors
Chapman JG,Magee WP,Stukenbrok HA,Beckius GE,Milici AJ,Tracey WRdoi
10.1016/s0014-2999(02)02484-6keywords:
subject
Has Abstractpub_date
2002-12-05 00:00:00pages
59-68issue
1-3eissn
0014-2999issn
1879-0712pii
S0014299902024846journal_volume
456pub_type
杂志文章abstract：:The effects of the dopamine D2 receptor agonist quinpirole (LY 171555) on locomotor activity and margin time (thigmotaxis or wall-hugging) were measured for 2 h in rats injected either s.c. (vehicle, 0.02, 2.0 mg/kg) or directly into either the dorsal striatum or nucleus accumbens (vehicle, 0.1, 1.0, 10, 20 or 40 micr...
journal_title：European journal of pharmacology
pub_type： 杂志文章
doi：10.1016/0014-2999(92)90091-h
更新日期：1992-04-07 00:00:00
abstract：:First line antidepressants are the so-called SSRIs (selective serotonin reuptake inhibitors), e.g. fluvoxamine, fluoxetine, sertraline, paroxetine and escitalopram. Unfortunately, these drugs mostly do not provide full symptom relief and have a slow onset of action. Therefore other antidepressants are also being presc...
journal_title：European journal of pharmacology
pub_type： 杂志文章,评审
doi：10.1016/j.ejphar.2014.11.045
更新日期：2015-04-15 00:00:00
abstract：:The family of facilitative glucose transporter (GLUT) proteins is responsible for the entry of glucose into cells throughout the periphery and the brain. The expression, regulation and activity of GLUTs play an essential role in neuronal homeostasis, since glucose represents the primary energy source for the brain. Br...
journal_title：European journal of pharmacology
pub_type： 杂志文章,评审
doi：10.1016/j.ejphar.2004.02.041
更新日期：2004-04-19 00:00:00
abstract：:Goniothalamin, a natural occurring styryl-lactone, is a novel compound with putative anticancer activities. In the present study, the mechanism of action of goniothalamin was further investigated in human breast cancer MDA-MB-231 cells. Goniothalamin treatment of cells significantly induced cell cycle arrest at G(2)/M...
journal_title：European journal of pharmacology
pub_type： 杂志文章
doi：10.1016/j.ejphar.2005.08.047
更新日期：2005-10-17 00:00:00
abstract：:Intravenous injection of ovalbumin into actively and passively sensitized guinea-pig resulted in acute circulatory collapse. The plasma level of immunoreactive endothelin rose from 22 +/- 2 to 40 +/- 7 fmol/ml (n = 12, P < 0.01) and 29 +/- 5 fmol/ml (n = 12, P < 0.01) in actively and passively sensitized animals, resp...
journal_title：European journal of pharmacology
pub_type： 杂志文章
doi：10.1016/0014-2999(93)91001-4
更新日期：1993-08-03 00:00:00
abstract：:Gastric lesions were provoked in all rats that had received intraperitoneally a single dose of the dopamine antagonists haloperidol, metoclopramide or domperidone 24 h before. Dose-dependence was demonstrated for haloperidol. This drug induced gastric lesions as early as 90 min after its application. The ulcerogenic e...
journal_title：European journal of pharmacology
pub_type： 杂志文章
doi：10.1016/0014-2999(86)90522-4
更新日期：1986-11-12 00:00:00
abstract：:In the present study, we reported the metabolic effects of salidroside, one of the active components of Rhodiola Rosea, on skeletal muscle cells. Salidroside dose-dependently stimulated glucose uptake in differentiated L6 rat myoblast cells. Inhibitor of AMP-activated protein kinase (AMPK) by pretreating the cells wit...
journal_title：European journal of pharmacology
pub_type： 杂志文章
doi：10.1016/j.ejphar.2008.04.036
更新日期：2008-07-07 00:00:00
abstract：:The corticotropin releasing factor (CRF) family includes CRF and urocortin. The effects of urocortin and CRF (0.3, 1, 3 and 10 nmol/kg, i.v.) relative to those of vehicle (0.9% NaCl) on mean arterial pressure and mean circulatory filling pressure (index of venous tone) were examined in conscious, unrestrained rats tha...
journal_title：European journal of pharmacology
pub_type： 杂志文章
doi：10.1016/j.ejphar.2005.01.022
更新日期：2005-03-07 00:00:00
abstract：:Influenza is a major disease in humans. The reemergence of avian influenza A viruses has indicated that hyperinflammatory responses are closely related to the severity of disease. Influenza virus infection induces nuclear transcription factor kappaB (NF-kappaB) activation. NF-kappaB and NF-kappaB-dependent gene produc...
journal_title：European journal of pharmacology
pub_type： 杂志文章
doi：10.1016/j.ejphar.2006.03.073
更新日期：2006-07-17 00:00:00
abstract：:In isolated spontaneously beating right and left atria and in electrically driven left atrium from rat, endothelin-1 increased the rate and force of contraction, but significantly decreased the positive chronotropic and inotropic responses to sympathetic nerve stimulation. The decrease may be partly dependent on the p...
journal_title：European journal of pharmacology
pub_type： 杂志文章
doi：10.1016/0014-2999(91)90102-v
更新日期：1991-03-05 00:00:00
abstract：:The purpose of this study was to investigate whether high conductance Ca2+-activated K+ channels (BK(Ca)) are mediating the vasodilator action of hydralazine. In isolated porcine coronary arteries, hydralazine (1-300 microM), like the K+ channel opener levcromakalim, preferentially relaxed contractions induced by K+ (...
journal_title：European journal of pharmacology
pub_type： 杂志文章
doi：10.1016/s0014-2999(98)00701-8
更新日期：1998-11-13 00:00:00
abstract：:Using urethane-anesthetized rats, we examined whether an activation of nuclear factor kappa B is involved in the corticotropin-releasing factor-induced increase in plasma levels of catecholamines. An intracerebroventricularly administered corticotropin-releasing factor (1.5 nmol/animal)-induced increase of plasma cate...
journal_title：European journal of pharmacology
pub_type： 杂志文章
doi：10.1016/j.ejphar.2008.01.037
更新日期：2008-04-14 00:00:00
abstract：:The effects of (-)-N(1)phenethyl-norcymserine (PEC, 5 mk/kg, i.p.) on acetylcholine release and cholinesterase activity in the rat cerebral cortex were compared with those of donepezil (1 mg/kg, i.p.), a selective acetylcholinesterase inhibitor, and rivastigmine (0.6 mg/kg, i.p.), an inhibitor of acetylcholinesterase ...
journal_title：European journal of pharmacology
pub_type： 杂志文章
doi：10.1016/j.ejphar.2007.06.053
更新日期：2007-10-31 00:00:00
abstract：:The distribution of the binding of [3H]GR65630 (0.2 nM) to putative 5-HT3 recognition sites in the brain of the common marmoset was assessed using autoradiography. Specific binding was heterogeneously distributed with the highest densities found in discrete nuclei of the lower medulla (nucleus tractus solitarii, dorsa...
journal_title：European journal of pharmacology
pub_type： 杂志文章
doi：10.1016/0014-2999(92)90609-8
更新日期：1992-04-29 00:00:00
abstract：:Analogues of the C-terminal octapeptide of cholecystokinin (CCK) modified in the Met28-Gly29 region, were tested for their ability to interact with peripheral cholecystokinin receptors on rat pancreatic acini and to stimulate amylase secretion. These analogues were further evaluated for their ability to recognize cent...
journal_title：European journal of pharmacology
pub_type： 杂志文章
doi：10.1016/0014-2999(90)90436-a
更新日期：1990-09-21 00:00:00
abstract：:Paclitaxel, an antitumoral drug, was used in a single dose (29 mg/kg i.p.) as an injury agent for inducing transient suppression of hematopoiesis in a murine experimental model during 10days. The aim of this study focuses on erythropoietin (EPO) receptor, GATA binding protein 1 (globin transcription factor 1) (GATA-1)...
journal_title：European journal of pharmacology
pub_type： 杂志文章
doi：10.1016/j.ejphar.2010.02.056
更新日期：2010-06-25 00:00:00
abstract：:The existence of presynaptic autoreceptors modulating acetylcholine release from central cholinergic nerve endings was investigated by using rat hippocampal synaptosomes in a superfusion system. The presence of exogenous acetylcholine, carbachol or oxotremorine in the superfusion fluid produced a dose-dependent inhibi...
journal_title：European journal of pharmacology
pub_type： 杂志文章
doi：10.1016/0014-2999(81)90147-3
更新日期：1981-07-17 00:00:00
abstract：:Complete control of emesis caused by cyclophosphamide (CPA) is of immense interest to both patients and physicians. Serotonin 5-HT3- and tachykinin NK1-receptor antagonists are widely used antiemetics in clinic, but they fail to completely control CPA-induced emesis. New antiemetic targets for the full control of CPA-...
journal_title：European journal of pharmacology
pub_type： 杂志文章
doi：10.1016/j.ejphar.2013.09.080
更新日期：2014-01-05 00:00:00
abstract：:Here we investigated the effect of naloxone-precipitated morphine withdrawal on the release of noradrenaline in hippocampus of the anaesthetised rat. Naloxone (1 mg/kg i.p.) injected 3 and 24 h, but not 3 weeks, after eight daily injections of morphine, induced an immediate increase in hippocampal noradrenaline releas...
journal_title：European journal of pharmacology
pub_type： 杂志文章
doi：10.1016/0014-2999(92)90052-6
更新日期：1992-05-14 00:00:00
abstract：:Acid-sensing ion channels (ASICs), a family of proton-gated cation channels, are believed to mediate pain caused by extracellular acidification. Gastrodin is a main bioactive constituent of the traditional herbal Gastrodia elata Blume, which has been widely used in Oriental countries for centuries. As an analgesic, ga...
journal_title：European journal of pharmacology
pub_type： 杂志文章
doi：10.1016/j.ejphar.2014.02.044
更新日期：2014-05-15 00:00:00
abstract：:For the development of efficient pulmonary delivery systems for protein and peptide drugs, it is important to understand their transport mechanisms in alveolar epithelial cells. In this study, the uptake mechanism for FITC-insulin in cultured alveolar epithelial cell line RLE-6TN was elucidated. FITC-insulin uptake by...
journal_title：European journal of pharmacology
pub_type： 杂志文章
doi：10.1016/j.ejphar.2011.10.003
更新日期：2011-12-15 00:00:00
abstract：:Certain enkephalin analogues, including those which contain the conformationally restricted amino acid E-(2R,3S)-cyclopropylphenylalanine [2R,3S)-delta E Phe), have been shown to have high affinity for brain delta opioid receptors but are much less active in mouse vas deferens bioassays. To investigate whether there a...
journal_title：European journal of pharmacology
pub_type： 杂志文章
doi：10.1016/0014-2999(90)90556-l
更新日期：1990-02-20 00:00:00
abstract：:The mucociliary activity of the rabbit maxillary sinus is increased after exposure to airway irritants such as cigarette smoke and capsaicin. This effect is partly due to a cholinergic reflex but involves an atropine-resistant response probably mediated by the release of tachykinins such as substance P or neurokinin A...
journal_title：European journal of pharmacology
pub_type： 杂志文章
doi：10.1016/0014-2999(93)90113-v
更新日期：1993-02-16 00:00:00
abstract：:Excessive intracellular accumulation of zinc (Zn(2+)) is neurotoxic and contributes to a number of neuropathological conditions. Here, we investigated the protective effect of 3-morpholinosydnonimine (SIN-1) against Zn(2+)-induced neuronal cell death in differentiated PC12 cells. We found that Zn(2+)-induced PC12 cell...
journal_title：European journal of pharmacology
pub_type： 杂志文章
doi：10.1016/j.ejphar.2014.12.003
更新日期：2015-02-05 00:00:00
abstract：:This paper reports the in vitro and in vivo characterisation of a nonpeptide, orally active, vasopressin V(1A) and V(2) receptor antagonist, YM087 (methyl-1,4,5,6-tetrahydroimidazo[4, 5-d][1]benzoazepine-6-carbonyl)-2-phenylbenzanilide monohydrochloride) in the rat. YM087 dose dependently displaced the vasopressin V(1...
journal_title：European journal of pharmacology
pub_type： 杂志文章
doi：10.1016/s0014-2999(99)00530-0
更新日期：1999-09-17 00:00:00
abstract：:Clonidine and other imidazolines, including phentolamine, inhibited the norepinephrine-elicited accumulation of cyclic AMP in brain slices via blockade or postsynpatic alpha-adrenoceptors. Clonidine (0.0125--0.050 mg/kg, i.p.) antagonized the increase in locomotor activity induced by amphetamine in a dose-dependent ma...
journal_title：European journal of pharmacology
pub_type： 杂志文章
doi：10.1016/0014-2999(78)90126-7
更新日期：1978-02-15 00:00:00
abstract：:Denudatin B is an antiplatelet agent isolated from the flower buds of Magnolia fargesii. We studied the effects of denudatin B on the vasoconstriction of rat thoracic aorta induced by high potassium (K+) solution, norepinephrine (NE) and caffeine, and to elucidate its mode of action. The contraction of rat aorta cause...
journal_title：European journal of pharmacology
pub_type： 杂志文章
doi：10.1016/0014-2999(90)90338-7
更新日期：1990-10-02 00:00:00
abstract：:Cachexia is the main cause of mortality in advanced cancer patients. We investigated the effects of insulin (INS) and glutamine dipeptide (GDP), isolated or associated, on cachexia and metabolic changes induced by Walker 256 tumor in rats. INS (NPH, 40 UI/kg, sc) or GDP (1.5g/kg, oral gavage) was once-daily administer...
journal_title：European journal of pharmacology
pub_type： 杂志文章
doi：10.1016/j.ejphar.2017.03.010
更新日期：2017-07-05 00:00:00
abstract：:The effects of the serotonin (5-HT) precursor L-tryptophan on MDMA (3,4-methylenedioxymethamphetamine)-induced inhibition of dorsal raphe neuronal firing were characterized using extracellular single-unit recording and microdialysis techniques in the in vitro midbrain slice preparation. Pretreatment with L-tryptophan ...
journal_title：European journal of pharmacology
pub_type： 杂志文章
doi：10.1016/0014-2999(90)90110-r
更新日期：1990-03-27 00:00:00
abstract：:The influence of native low-density lipoprotein (LDL) on the inhibition of endothelium-dependent relaxation previously induced by oxidized LDL was investigated with intact rabbit aortic rings. We also tried to assess oxysterol involvement in the native lipoprotein effects. Lipoprotein fractions (1 mg protein/ml) were ...
journal_title：European journal of pharmacology
pub_type： 杂志文章
doi：10.1016/s0014-2999(00)00696-8
更新日期：2000-10-20 00:00:00
