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 PPARalpha activation of macrophages on the modulation of the tumor necrosis factor alpha (TNFalpha) expression in adipocytes using a cell culture system. A conditioned medium of lipopolysaccharide (LPS)-stimulated RAW264.7 cells, a macrophage cell line, induced the level of TNFalpha mRNA in 3T3-L1 adipocytes. This effect was inhibited by the addition of neutralizing antibody against interleukin 6 (IL-6) in the conditioned medium or the preincubation of RAW264.7 cells with a specific PPARalpha agonist, K-111 (2,2-dichloro-12-(4-chlorophenyl)dodecanoic acid). K-111 reduced both the IL-6 production and mRNA expression in RAW264.7 cells, and its effect was stronger than that of rosiglitazone, a PPARgamma agonist. The activation of the stress-activated protein kinase/c-Jun NH2-terminal kinase (SAPK/JNK) pathway and nuclear factor kappa B (NF-kappaB) subunits of p65 was significantly inhibited by K-111. The blocking of IL-6 production through the SAPK/JNK pathway or by transfection with siRNA specific for IL-6 abolished the inhibitory effect of K-111 on the TNFalpha expression in the 3T3-L1 adipocytes. As a result, the IL-6 produced by RAW264.7 cells is an inducer of TNFalpha expression in 3T3-L1 adipocytes, and the IL-6 secretion is inhibited by the activation of PPARalpha. The PPARalpha activators may suppress the pathogenetical secretion of TNFalpha in the adipocytes through the functional modulation of the infiltrated macrophages.
journal_name
Eur J Pharmacoljournal_title
European journal of pharmacologyauthors
Murakami K,Bujo H,Unoki H,Saito Ydoi
10.1016/j.ejphar.2006.12.037subject
Has Abstractpub_date
2007-04-30 00:00:00pages
206-13issue
1-3eissn
0014-2999issn
1879-0712pii
S0014-2999(07)00059-3journal_volume
561pub_type
杂志文章abstract::Lithium is widely used for the management of neuropsychiatric symptoms in bipolar disorders. A variety of hypotheses have been invoked to explain the mechanism of action of lithium. To determine if lithium exerts direct cardiac protection, in the present study perfused rat heart model was used. The mechanism of lithiu...
journal_title:European journal of pharmacology
pub_type: 杂志文章
doi:10.1016/j.ejphar.2008.08.010
更新日期:2008-11-12 00:00:00
abstract::According to the American Society of Clinical Oncology or ASCO's clinical practice guidelines, administration of Tamoxifen for hormone receptor positive patients improved outcomes. However, many studies have been conducted in this issue, with the rise of Tamoxifen resistance in recent decades. There are many alternati...
journal_title:European journal of pharmacology
pub_type: 杂志文章,评审
doi:10.1016/j.ejphar.2017.03.026
更新日期:2017-06-05 00:00:00
abstract::Endothelium injury is a primary event in atherogenesis, which is followed by monocyte infiltration, macrophage differentiation, and smooth muscle cell migration. Peroxisome proliferator-activated receptors (PPARs) are transcription factors now recognized as important mediators in the inflammatory response. The aim of ...
journal_title:European journal of pharmacology
pub_type: 杂志文章
doi:10.1016/s0014-2999(01)01589-8
更新日期:2002-01-25 00:00:00
abstract::Fenfluramine + phentermine was a widely used combination for weight loss. Fenfluramine and phentermine are believed to act via serotonin and catecholamines, respectively. To what extent these drugs interact has not been well-established. We compared the anorectic efficacy of a range of doses of the combination (using ...
journal_title:European journal of pharmacology
pub_type: 杂志文章
doi:10.1016/s0014-2999(99)00235-6
更新日期:1999-06-04 00:00:00
abstract::HgCl2 and mersalyl increased and later decreased both the spontaneous and evoked transmitter liberation at the frog neuromuscular junction. Lower concentration of HgCl2 exhibited only an inhibitory effect on transmitter release. These mercurials inhibited calcium transport of mitochondria and synaptosomal vesicles. Lo...
journal_title:European journal of pharmacology
pub_type: 杂志文章
doi:10.1016/0014-2999(78)90438-7
更新日期:1978-10-15 00:00:00
abstract::Acetylshikonin, a naphthoquinone isolated from the Chinese herb medicine, tzu ts'ao, was demonstrated to inhibit the polymyxin B-induced hind-paw edema in normal as well as in adrenalectomized mice. Liver glycogen content was increased in adrenalectomized mice pretreated with dexamethasone, but not with acetylshikonin...
journal_title:European journal of pharmacology
pub_type: 杂志文章
doi:10.1016/0014-2999(94)00627-j
更新日期:1995-01-05 00:00:00
abstract::We studied the effects of 2-(allyl-1-piperazinyl)-4-n-amyloxyquinazoline fumarate (KB-5666) on brain edema and histological neuronal damage in rats with focal ischemia and on lipid peroxidation in brain homogenates and brain mitochondria in vitro. KB-5666 (3-100 microM) inhibited lipid peroxidation in brain homogenate...
journal_title:European journal of pharmacology
pub_type: 杂志文章
doi:10.1016/0014-2999(91)90367-y
更新日期:1991-05-02 00:00:00
abstract::We have examined the motor responses to the dopamine D(3) receptor-preferring agonist, S(+)-(4aR,10bR)-3,4,4a, 10b-tetrahydro-4-propyl-2H,5H-1-benzopyranol[4,3-b]-1,4-oxazin+ ++-9-ol ((+)-PD128,907), by non-habituated male rats during postnatal development. (+)-PD128,907 (0.025 and 0.1 mg/kg) increased motor activity ...
journal_title:European journal of pharmacology
pub_type: 杂志文章
doi:10.1016/s0014-2999(00)00112-6
更新日期:2000-03-24 00:00:00
abstract::The aim of this study was to determine the effects of 4-(4-bromophenyl)-5-(3-chlorophenyl)-2,4-dihydro-3H-1,2,4-triazole-3-thione (TP4-a new S-triazole derivative possessing anticonvulsant properties in preclinical studies) on the protective action of four different classical antiepileptic drugs (carbamazepine, phenob...
journal_title:European journal of pharmacology
pub_type: 杂志文章
doi:10.1016/j.ejphar.2012.06.023
更新日期:2012-09-05 00:00:00
abstract::Stimulation of [35S]GTPgammaS binding by serotonin (5-hydroxytryptamine, 5-HT) receptor ligands was characterized in rat hippocampal membranes. The optimized assay contained 30-50 microg protein, 300 microM GDP and 0.1 nM [35S]GTPgammaS, incubated at 37 degrees C for 20 min. At 10 microM, the 5-HT1A receptor agonist R...
journal_title:European journal of pharmacology
pub_type: 杂志文章
doi:10.1016/s0014-2999(97)01547-1
更新日期:1998-02-19 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 effects of (S)-nafenodone, a new antidepressant, were studied on contraction and 45Ca2+ fluxes in rat vascular smooth muscle. In isolated rat aorta (S)-nafenodone, 10(-7) - 10(-4) M, inhibited the contractions induced by 80 mM KCl (IC50 = 1.4 +/- 0.4 x 10(-5) M) and 10(-5) M noradrenaline (IC50 = 1.2 +/- 0.2 x 10(...
journal_title:European journal of pharmacology
pub_type: 杂志文章
doi:10.1016/0014-2999(93)90734-y
更新日期:1993-02-23 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::The effects of 26 anesthetic agents were studied on the rhythmical discharge activity of a single isolated neuron (crayfish stretch receptor). Many of these agents produced concentration-dependent biphasic responses (excitation and depression), and some also induced altered discharge patterns (burst activity). The dom...
journal_title:European journal of pharmacology
pub_type: 杂志文章
doi:10.1016/0014-2999(87)90495-x
更新日期:1987-07-02 00:00:00
abstract::The appearance of nephrotic syndromes such as proteinuria, hypoalbuminemia, hypercholesterolemia and increase in blood nitrogen urea, induced in rats by injection of puromycin aminonucleoside was markedly inhibited by oral administration of Dup 753 (losartan), a novel angiotensin II receptor antagonist, at a dose of 1...
journal_title:European journal of pharmacology
pub_type: 杂志文章
doi:10.1016/0014-2999(93)90609-l
更新日期:1993-05-19 00:00:00
abstract::The effect of potassium on the binding of digoxin or digoxigenin to isolated Na+, K+-ATPase was compared with that of potassium on the positive inotropic action of the agents in guinea-pig hearts. The binding of digoxigenin to the enzyme in vitro was reduced to a greater extent by potassium than was the binding of dig...
journal_title:European journal of pharmacology
pub_type: 杂志文章
doi:10.1016/0014-2999(79)90497-7
更新日期:1979-08-15 00:00:00
abstract::Mouse GluK5 was expressed in Sf9 insect cells and radiolabelled with [(3)H]-kainate in receptor binding assays (Kd=6.9nM). Western immunoblotting indicated an Sf9 GluK5 band doublet corresponding to the glycosylated (128kDa) and deglycosylated (111kDa) protein, which was identical to the band pattern of native rat bra...
journal_title:European journal of pharmacology
pub_type: 杂志文章
doi:10.1016/j.ejphar.2016.06.049
更新日期:2016-10-05 00:00:00
abstract::The effects of an inhibitor of calmodulin, trifluoperazine (TFP), were determined on the electrical activity of cultured cell reaggregates derived from chick embryonic hearts (15-day-old). The cells exhibited naturally occurring slowly rising action potentials (APs) having a maximum rate of rise (+Vmax) of less than 3...
journal_title:European journal of pharmacology
pub_type: 杂志文章
doi:10.1016/0014-2999(84)90645-9
更新日期:1984-10-01 00:00:00
abstract::Apelin, a ligand for apelin-angiotension receptor-like 1 (APJ), has recently been shown to be a potent positive inotropic agent in normal hearts. In humans, levels of apelin have been shown to rise in early-stage heart failure and to fall in late-stage heart failure. In this study, we tested the hypothesis that apelin...
journal_title:European journal of pharmacology
pub_type: 杂志文章
doi:10.1016/j.ejphar.2006.09.034
更新日期:2006-12-28 00:00:00
abstract::In pregnant rat myometrium, isoproterenol (10(-8) M) inhibited spontaneous contractions without causing hyperpolarization. Isoproterenol (10(-6) M) relaxed the depolarized muscle without affecting the membrane potential. The presence of 80 mM Na+ did not affect the degree of high-K+ depolarization. It was also without...
journal_title:European journal of pharmacology
pub_type: 杂志文章
doi:10.1016/0014-2999(79)90045-1
更新日期:1979-11-23 00:00:00
abstract::The genes encoding the alpha3, alpha5 and beta4 subunits of nicotinic acetylcholine receptors are tightly clustered within the genome. As these three subunits constitute the predominant acetylcholine receptor subtype expressed in the peripheral nervous system, their genomic proximity suggests a regulatory mechanism en...
journal_title:European journal of pharmacology
pub_type: 杂志文章
doi:10.1016/s0014-2999(99)00884-5
更新日期:2000-03-30 00:00:00
abstract::Cats were treated once daily for 35 days with flurazepam (FZP). Different groups received 2, 5 or 20 mg/kg per day. A fourth group was started at 20 mg/kg per day, then the dose was increased to 30, and finally 40 mg/kg per day. Muscle relaxation, ataxia, and other measures of neurological impairment were used to meas...
journal_title:European journal of pharmacology
pub_type: 杂志文章
doi:10.1016/0014-2999(82)90100-5
更新日期:1982-07-16 00:00:00
abstract::In the presence of l-serine borate, salbutamol was much more effective in reversing rather than preventing LTC4-induced contractions of guinea-pig trachea. This suggests that different mechanisms are involved in initiating versus maintaining LTC4-induced contractions. In addition, the ability of salbutamol pretreatmen...
journal_title:European journal of pharmacology
pub_type: 杂志文章
doi:10.1016/0014-2999(86)90066-x
更新日期:1986-07-31 00:00:00
abstract::In the spinal cord of the pentobarbitone-anaesthetised cat, microelectrophoretic pitrazepin reduced the inhibitory effects on neuronal firing of both glycine and GABA. ...
journal_title:European journal of pharmacology
pub_type: 杂志文章
doi:10.1016/0014-2999(86)90590-x
更新日期:1986-11-19 00:00:00
abstract::The adult brain has long been viewed as a collection of neuronal networks that maintain a fixed configuration of synaptic connections. Brain plasticity and learning was thought to depend exclusively on changes in the gain and offset of these connections. Over the last 50 years, molecular and cellular studies of neurop...
journal_title:European journal of pharmacology
pub_type: 杂志文章,评审
doi:10.1016/j.ejphar.2013.07.020
更新日期:2013-11-05 00:00:00
abstract::In view of the co-localization of spinal delta- and kappa-opioid receptors, we have investigated the interaction of selective opioid receptor agonists and antagonists in the spinal cord of mice in order to determine if these receptors are organized as heteromers. The finding that norbinaltorphimine (kappa) antagonized...
journal_title:European journal of pharmacology
pub_type: 杂志文章
doi:10.1016/s0014-2999(03)01599-1
更新日期:2003-04-25 00:00:00
abstract::FR 172357, a new non-peptide antagonist of the kinin B(2) receptor was tested in three isolated vessels, the human umbilical vein, the rabbit jugular vein, and the pig coronary artery, to evaluate its antagonistic activities against bradykinin. FR 172357 displaced to the right the concentration-response curves of brad...
journal_title:European journal of pharmacology
pub_type: 杂志文章
doi:10.1016/s0014-2999(99)00711-6
更新日期:1999-12-10 00:00:00
abstract::The decrease in blood flow in response to dopamine (DA) injected intraarterially (i.a.) into the femoral or renal vascular beds was examined in the anaesthetised dog. DA or noradrenaline (NA) were 10 times more potent as vasoconstrictor agents in the femoral than in the renal vasculature. In the femoral bed, the DA in...
journal_title:European journal of pharmacology
pub_type: 杂志文章
doi:10.1016/0014-2999(85)90448-0
更新日期:1985-02-05 00:00:00
abstract::Dextrans of molecular weight 10(4) to 2 x 10(6) induced histamine release from rat peritoneal mast cells in the presence of calcium (1 mM) and phosphatidyl serine (10 micrograms/ml). Glucose and low molecular weight dextrans inhibited the histamine release induced by high molecular weight dextrans but the inhibition c...
journal_title:European journal of pharmacology
pub_type: 杂志文章
doi:10.1016/0014-2999(82)90287-4
更新日期:1982-09-10 00:00:00
abstract::We evaluated the inhibitory activity of a novel prostacyclin analog, OP-2507 (15-cis-(4-n-propylcyclohexyl)-16,17,18,19,20-pentanor-9-deo xy-6,9 alpha- nitriloprostaglandin F1 methyl ester) on the brain edema induced by occlusion of the middle cerebral artery in cats. Middle cerebral artery occlusion for 4h caused a d...
journal_title:European journal of pharmacology
pub_type: 杂志文章
doi:10.1016/0014-2999(88)90836-9
更新日期:1988-07-26 00:00:00