Abstract:
:β-Methoxyacrylate antibiotics are well known to inhibit the fungal and yeast mitochondrial respiratory chain. In addition, β-methoxyacrylates are reported to suppress the proliferation of mammalian cancer cells. Differentiation and cell-cycle arrest are closely related. The cell cycle of proliferating cells is suppressed before differentiation. In this study, we synthesized a β-methoxyacrylate analog and treated neuronal differential model cells with it. We then estimated β-methoxyacrylate's neurotrophic effect by inhibiting cell proliferation so as to orient neuronal differentiation. SUTAF-027-a novel β-methoxyacrylate derivative, arrested the cell cycle and thereby suppressed the proliferation of PC12 rat pheochromocytoma cells and mouse neuroblastoma Neuro2a cells at very low treatment doses, as low as 1nM. However, a single SUTAF-027 treatment did not affect neuritogenesis. Surprisingly, however, co-treatment of SUTAF-027 and nerve growth factor (NGF) significantly augmented the NGF-induced neurite outgrowth of PC12. On the other hand, a single treatment of 1nM SUTAF-027 induced neurite outgrowth in Neuro2a cells. Further signal transduction mechanism studies revealed that SUTAF-027 induced the phosphorylation of extracellular signal-regulated kinase (ERK) and slight phosphorylation of c-jun N-terminal kinase (JNK). Moreover, inhibition of ERK and JNK blocked SUTAF-027-augmented neurite outgrowth. These results suggested that the novel β-methoxyacrylate analog SUTAF-027 augmented neurite outgrowth by arresting the cell cycle and activating the ERK and JNK pathways.
journal_name
Eur J Pharmacoljournal_title
European journal of pharmacologyauthors
Nagahara Y,Suzuki E,Sekine Y,Uchiro H,Yoshimi Y,Shinomiya T,Ikekita Mdoi
10.1016/j.ejphar.2012.08.018subject
Has Abstractpub_date
2012-11-05 00:00:00pages
53-9issue
1-3eissn
0014-2999issn
1879-0712pii
S0014-2999(12)00729-7journal_volume
694pub_type
杂志文章abstract::The anticonvulsant effect of cannabinoids has been shown to be mediated through activation of the cannabinoid CB(1) receptor. This study was initiated to evaluate the effects of endogenously occurring cannabinoids (endocannabinoids) on seizure severity and threshold. The anticonvulsant effect of the endocannabinoid, a...
journal_title:European journal of pharmacology
pub_type: 杂志文章
doi:10.1016/s0014-2999(02)02331-2
更新日期:2002-10-11 00:00:00
abstract::In prehydrated rats, the administration of kappa-opiate agonists such as bremazocine, ethylketocyclazocine or compound Upjohn-50,488 produced a dose-dependent increase in urine output and decreased the concentration of Na+ and K+ in the urine as compared to that of saline-treated rats. The diuretic effect of bremazoci...
journal_title:European journal of pharmacology
pub_type: 杂志文章
doi:10.1016/0014-2999(84)90084-0
更新日期:1984-12-15 00:00:00
abstract::Ca(V)2.1 is highly expressed in the nervous system and plays an essential role in the presynaptic modulation of neurotransmitter release machinery. Recently, the antiepileptic drug levetiracetam was reported to inhibit presynaptic Ca(V)2.1 functions, reducing glutamate release in the hippocampus, although the precise ...
journal_title:European journal of pharmacology
pub_type: 杂志文章
doi:10.1016/j.ejphar.2010.07.029
更新日期:2010-10-25 00:00:00
abstract::The administration of high doses of methamphetamine causes the degeneration of striatal dopaminergic fibers in the brains of rodents, and oxidative stress appears to be one of the main factors of neurotoxicity. This study examined whether edaravone, a radical scavenger, protects against methamphetamine-induced neuroto...
journal_title:European journal of pharmacology
pub_type: 杂志文章
doi:10.1016/j.ejphar.2006.05.012
更新日期:2006-08-07 00:00:00
abstract::Mitochondrial DNA mutations promote hypertensive renal dysfunction, but the molecular mechanism remains unclear. This study compared renal damage between spontaneously hypertensive rats (SHR) and SHR with mitochondrial transfer (t)RNA mutations. To investigate the role of mitochondrial outer membrane voltage-dependent...
journal_title:European journal of pharmacology
pub_type: 杂志文章
doi:10.1016/j.ejphar.2019.172622
更新日期:2019-12-15 00:00:00
abstract::We tested the hypothesis that relaxation of the rat mesenteric artery in response to insulin is mediated by K(+) channels. Two concentrations of insulin (10 and 100 mU/ml) induced relaxation of the artery by 6+/-1%, 24+/-3% (mean+/-S.E.M.). Denudation of the endothelium or precontraction by KCl (30 mM), clotrimazole (...
journal_title:European journal of pharmacology
pub_type: 杂志文章
doi:10.1016/s0014-2999(00)00892-x
更新日期:2001-01-05 00:00:00
abstract::Removal of the epithelium increased the responsiveness of isolated guinea-pig trachea to the contractile effects of endothelin. This phenomenon was observed in the presence of indomethacin (5 microM), captopril (10 microM), bacitracin (20 micrograms/ml) or leupeptin (50 microM), but was inhibited by phosphoramidon (10...
journal_title:European journal of pharmacology
pub_type: 杂志文章
doi:10.1016/0014-2999(89)90114-3
更新日期:1989-11-21 00:00:00
abstract::The activation of eosinophils with the lipid mediator, leukotriene B(4), induces their homotypic aggregation. Upon activation with leukotriene B(4), eosinophils release a significant amount of arachidonic acid, a process dependent on the activation of phospholipase A(2). Here, we have evaluated whether arachidonic aci...
journal_title:European journal of pharmacology
pub_type: 杂志文章
doi:10.1016/s0014-2999(99)00697-4
更新日期:1999-11-19 00:00:00
abstract::Ro 40-5967 [(1S,2S)-2-[2[3-(2-benzamidopropyl]- methylamino]ethyl]-6-fluoro-1,2,3,4-tetrahydro-1-isopropyl-2-naphthyl- methoxyacetate] is a new Ca2+ channel antagonist active at L-type channels. Radioligand binding studies in cardiac tissue show that Ro 40-5967 does not inhibit 1,4-dihydropyridine binding, but does in...
journal_title:European journal of pharmacology
pub_type: 杂志文章
doi:10.1016/0014-2999(95)00194-p
更新日期:1995-07-04 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::Stimulation of the right trigeminal ganglion in pentobarbital anaesthetised rats increased mean arterial blood pressure and decreased right carotid vascular resistance but had no effect on left carotid vascular resistance. Sumatriptan (0.3 mg/kg i.v.) pretreatment did not significantly affect basal levels or stimulati...
journal_title:European journal of pharmacology
pub_type: 杂志文章
doi:10.1016/0014-2999(95)00231-9
更新日期:1995-07-25 00:00:00
abstract::Rat and human alpha- and beta-calcitonin gene-related peptide (CGRP), in the concentration range 1-100 nM, produced sustained relaxations of longitudinal muscle from the rat fundus and guinea pig gastric corpus. The peptides were equipotent and equally effective. Tetrodotoxin, adrenoceptor and purine receptor antagoni...
journal_title:European journal of pharmacology
pub_type: 杂志文章
doi:10.1016/0014-2999(89)90612-2
更新日期:1989-03-14 00:00:00
abstract::To determine the role of protein kinase C in the regulation of intestinal fluid transport, experiments were performed with the rat jejunum in vivo, using the active phorbol ester, 4-beta-phorbol 12-myristate 13-acetate (PMA), as stimulator of protein kinase C. Intraluminally administered PMA dose dependently reversed ...
journal_title:European journal of pharmacology
pub_type: 杂志文章
doi:10.1016/0014-2999(90)90053-9
更新日期:1990-07-17 00:00:00
abstract::It is well established that the intracellular receptors of androgens act as transcription factors upon their activation by androgen binding. However, a growing number of studies have associated androgens with rapid biological responses independent of their classical action mechanism. In this sense, 5alpha- and 5beta-d...
journal_title:European journal of pharmacology
pub_type: 杂志文章
doi:10.1016/s0014-2999(01)01039-1
更新日期:2001-06-22 00:00:00
abstract::In rat brain cortex slices, ethanol was three times more potent in inhibiting [3H]noradrenaline ([3H]NA) release evoked by N-methyl-D-aspartate (NMDA) than in inhibiting the release evoked by kainic acid. Methanol, 1-propanol, 1-butanol, 1-pentanol and 1-hexanol shared the inhibitory property of ethanol on NMDA-evoked...
journal_title:European journal of pharmacology
pub_type: 杂志文章
doi:10.1016/0014-2999(90)94152-n
更新日期:1990-11-27 00:00:00
abstract::Vasoactive substances released from aggregating platelets inhibit beta-adrenergic neurotransmission in coronary arteries. Studies were carried out on the effects of two such vasoactive substances on canine coronary arteries, at concentrations equivalent to that released by platelets under physiological conditions. 5-H...
journal_title:European journal of pharmacology
pub_type: 杂志文章
doi:10.1016/0014-2999(87)90030-6
更新日期:1987-01-20 00:00:00
abstract::CGP 11305 A (4-(5-methoxy-7-bromo-benzofuranyl)2-piperidine-HCl) inhibited serotonin (5-HT) deamination in brains and livers of pretreated rats. The ED50S were 1 and 0.7 mg/kg p.o., respectively. Phenylethylamine (PEA) deamination was only marginally affected up to doses of 100 mg/kg p.o. The duration of action of the...
journal_title:European journal of pharmacology
pub_type: 杂志文章
doi:10.1016/0014-2999(83)90443-0
更新日期:1983-10-14 00:00:00
abstract::The purpose of our study was to examine whether a significant interaction occurs between NMDA and non-NMDA receptor antagonists on respiratory function. For this purpose chloralose-anesthetized cats were used and respiratory minute volume (VE), tidal volume (Vt) respiratory rate (f), inspiratory and expiratory duratio...
journal_title:European journal of pharmacology
pub_type: 杂志文章
doi:10.1016/0014-2999(94)90569-x
更新日期:1994-01-24 00:00:00
abstract::Contractile responses to endothelin, 5-hydroxytryptamine (5-HT), noradrenaline and potassium were obtained on isolated preparations of pulmonary artery from rats made pulmonary hypertensive by an injection of monocrotaline (105 mg/kg s.c.) 4 weeks previously. When compared with data obtained in control rats, the poten...
journal_title:European journal of pharmacology
pub_type: 杂志文章
doi:10.1016/0014-2999(90)90524-a
更新日期:1990-02-06 00:00:00
abstract::Inhibitors of Na(+)/H(+) exchanger (NHE) 1 have been shown to exert protective effects on various myocardial injuries. In this study, we characterized the pharmacodynamic properties of new guanidine NHE1 inhibitors (cariporide, sabiporide, KR-32511, KR-32570, and KR-33028) to analyze their myocardial protective effect...
journal_title:European journal of pharmacology
pub_type: 杂志文章
doi:10.1016/j.ejphar.2007.03.056
更新日期:2007-07-12 00:00:00
abstract::Intravenous administration of 0.3 mg/kg of quinpirole to conscious rabbits that had been pretreated with domperidone caused a marked increase in blood pressure and renal sympathetic nerve activity with a peak at 5-10 min after injection (25% and 3-fold increase, respectively). Spectral analysis of the blood pressure-r...
journal_title:European journal of pharmacology
pub_type: 杂志文章
doi:10.1016/s0014-2999(99)00835-3
更新日期:2000-01-24 00:00:00
abstract::Eribis peptide 94 (EP 94) is a novel enkephalin analog, thought to interact with the μ- and δ-opioid receptors. The purpose of the present study was to examine the cardioprotective potential of EP 94 in two clinically relevant porcine models of myocardial ischaemia and reperfusion, and to investigate if such an effect...
journal_title:European journal of pharmacology
pub_type: 杂志文章
doi:10.1016/j.ejphar.2010.10.069
更新日期:2011-01-25 00:00:00
abstract::Increasing evidence displays that microRNAs (miRNAs) participate in the development of various human malignancies, including esophageal squamous cell carcinoma (ESCC). MicroRNA-33a-5p (miR-33a-5p) has recently been reported to function as a tumor suppressor in many human cancers. However, the expression and role of mi...
journal_title:European journal of pharmacology
pub_type: 杂志文章
doi:10.1016/j.ejphar.2019.172590
更新日期:2019-10-15 00:00:00
abstract::In the present study, we investigated the vasculoprotective effect of sigma-1 receptor stimulation with fluvoxamine on pressure overload hypertrophy-induced vascular injury in the thoracic aorta and defined mechanisms underlying that activity. Wistar rats underwent bilateral ovariectomy, and two weeks later were furth...
journal_title:European journal of pharmacology
pub_type: 杂志文章
doi:10.1016/j.ejphar.2010.10.055
更新日期:2011-01-15 00:00:00
abstract::Mizoribine is a disease-modifying anti-rheumatic drug (DMARD) that is used in the treatment of rheumatoid arthritis. However, clinical use of the drug is restricted to a few Asian countries due to a lack of comprehensive evidence on its effectiveness. The inhibitory effect of the drug on human osteoclastogenesis was i...
journal_title:European journal of pharmacology
pub_type: 杂志文章
doi:10.1016/j.ejphar.2008.12.048
更新日期:2009-03-01 00:00:00
abstract::Terfenadine, a histamine H(1) receptor antagonist, has been associated with clinical ventricular arrhythmias and in vitro excitation-conduction blocks, whereas anti-ischemic and antiarrhythmic effects have been shown with cicletanine, a prostacyclin generation stimulator. We aimed at determining in vitro if cicletanin...
journal_title:European journal of pharmacology
pub_type: 杂志文章
doi:10.1016/s0014-2999(99)00617-2
更新日期:1999-10-15 00:00:00
abstract::The use-dependent effects of bunazosin on the maximal rate of rise (Vmax) of the action potential and conduction velocity were studied in isolated papillary muscles of guinea-pig. Standard microelectrode techniques were used to monitor the conduction and action potential of the muscles. In the presence of 30 microM bu...
journal_title:European journal of pharmacology
pub_type: 杂志文章
doi:10.1016/0014-2999(90)94170-3
更新日期:1990-12-04 00:00:00
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...
journal_title:European journal of pharmacology
pub_type: 杂志文章
doi:10.1016/s0014-2999(02)02484-6
更新日期:2002-12-05 00:00:00
abstract::Pulmonary hypertension is a progressive disease of various origins that is associated with right ventricular dysfunction. In the present study, the protective effect of diosgenin was investigated in monocrotaline-induced pulmonary hypertension in rats. Pulmonary hypertension was induced by a single subcutaneous inject...
journal_title:European journal of pharmacology
pub_type: 杂志文章
doi:10.1016/j.ejphar.2014.07.026
更新日期:2014-10-05 00:00:00
abstract::Farrerol, a typical natural flavanone, is the major active component of Rhododendron dauricum L. The objective of this study was to evaluate the attenuation effect of farrerol against the aortic lesions in spontaneously hypertensive rats (SHR) for the first time. Twelve-week-old male SHR were orally administered with ...
journal_title:European journal of pharmacology
pub_type: 杂志文章
doi:10.1016/j.ejphar.2015.11.020
更新日期:2015-12-15 00:00:00