Abstract：
:Animal studies have shown that endogenous estrogens such as 17β-estradiol (E2) can modulate lipid profiles in vivo, and this effect is generally thought to be mediated by the estrogen receptors (ERs). The present study sought to test a hypothesis that some of the endogenous estrogen metabolites that have very weak estrogenic activity may exert some of their modulating effects on lipid metabolism in an ER-independent manner. Using ovariectomized female rats as an in vivo model, we found that 4-hydroxyestradiol (4-OH-E2) has a markedly stronger effect in reducing the adipocyte size and serum cholesterol level in rats compared to E2, despite the weaker estrogenic activity of 4-OH-E2. Moreover, when E2 or 4-OH-E2 is used in combination with ICI-182,780 (an ER antagonist), some of their lipid-modulating effects are not blocked by this antiestrogen. Interestingly, two of the O-methylation metabolites of 4-OH-E2, namely, 4-methoxyestradiol and 4-methoxyestrone, which have much weaker estrogenic activity, were also found to have similar lipid-modulating effects compared to 4-OH-E2. Mechanistically, up-regulation of the expression of leptin, cytochrome P450 7A1 and LXRα genes is observed in the liver of animals treated with E2 or 4-OH-E2, and the up-regulation is essentially not inhibited by co-treatment with ICI-182,780. These results demonstrate that some of the endogenous E2 metabolites are functionally important modulators of lipid metabolic profiles in vivo. In addition, our findings indicate that an ER-independent pathway likely mediates some of the lipid-modulating effects of endogenous estrogens and their metabolic derivatives.
journal_name
Eur J Pharmacoljournal_title
European journal of pharmacologyauthors
Wang P,Zhu BTdoi
10.1016/j.ejphar.2017.02.032subject
Has Abstractpub_date
2017-04-05 00:00:00pages
107-117eissn
0014-2999issn
1879-0712pii
S0014-2999(17)30098-5journal_volume
800pub_type
杂志文章abstract：:It is known that low-dose aspirin is effective in coronary artery therapy, although it has not yet been clarified how it exerts its action. Here, we report that treatment of coronary artery patients with 100 mg/day of aspirin does not attenuate thrombin generation, but reduces free thrombin by favouring the formation ...
journal_title：European journal of pharmacology
pub_type： 杂志文章
doi：10.1016/s0014-2999(02)02925-4
更新日期：2003-01-26 00:00:00
abstract：:A significant stimulatory action of PGE1 on adenylate cyclase of the particulate membrane preparation of rat heart was observed at 1 X 10(-4) M. PGE1 caused a positive inotropic effect on isolated spontaneously beating rat atria 1 X (10(-5) M, and an increase in atrial cyclic AMP level at 1 X 10(-6) M. PGE2 stimulate...
journal_title：European journal of pharmacology
pub_type： 杂志文章
doi：10.1016/0014-2999(78)90025-0
更新日期：1978-11-01 00:00:00
abstract：:The ontogenesis of kappa-opioid receptors has been studied in the postnatal period from day 5 to day 30 using the highly selective kappa-site ligand [3H]U-69593 in binding studies. Analyses of saturation curves revealed a marked increase in the binding capacities between day 5 and day 10 with no further increment in t...
journal_title：European journal of pharmacology
pub_type： 杂志文章
doi：10.1016/0014-2999(90)90157-2
更新日期：1990-01-03 00:00:00
abstract：:Risperidone (R 64 766, 3-[2-[4-(6-fluoro-1,2-benzisoxazol-3-yl)-1-pyperidinyl]ethyl )-6,7,8,9-tetrahydro-2-methyl-4H-pyrido[1,2-a]pyrimidin-4-one) has superior effects in treating negative symptoms of schizophrenia and causes less extrapyramidal side effects than traditional antipsychotics. In this study, we employed ...
journal_title：European journal of pharmacology
pub_type： 杂志文章
doi：10.1016/s0014-2999(99)00160-0
更新日期：1999-04-16 00:00:00
abstract：:Bacterial lipopolysaccharide and other immunostimulants induce gene expression of an isoform of nitric oxide synthase (iNOS) in vascular smooth muscle cells. This process is dependent on nuclear factor-kappa B (NF-kappa B) activation. The aim of this study was to investigate whether the NF-kappa B and Akt signaling pa...
journal_title：European journal of pharmacology
pub_type： 杂志文章
doi：10.1016/j.ejphar.2003.09.034
更新日期：2003-11-28 00:00:00
abstract：:Electrical stimulation produced a contraction in the isolated guinea-pig vas deferens. This response was blocked by tetrodotoxin, guanethidine and bretylium but not by atropine. The magnitude of the contractile response to electrical stimulation depended on the concentration of the external calcium. Sulfur-containing ...
journal_title：European journal of pharmacology
pub_type： 杂志文章
doi：10.1016/0014-2999(83)90262-5
更新日期：1983-11-11 00:00:00
abstract：:Apomorphine (50 micrograms/kg) induced repeated episodes of yawning, penile erection and genital grooming in rats. A dose of cycloheximide, which inhibited brain protein synthesis by 50% totally prevented apomorphine-induced yawning and reduced by approximately 50% the occurrence of episodes of penile erection and gen...
journal_title：European journal of pharmacology
pub_type： 杂志文章
doi：10.1016/0014-2999(82)90327-2
更新日期：1982-12-24 00:00:00
abstract：:The identification of adenylyl cyclase isoenzymes in mammalian host cells is important for the interpretation of data obtained from cell lines heterologously expressing G-protein coupled receptors. Reverse transcriptase polymerase chain reaction (RT-PCR) was used to amplify adenylyl cyclase cDNAs from Chinese hamster ...
journal_title：European journal of pharmacology
pub_type： 杂志文章
doi：10.1016/s0014-2999(98)00258-1
更新日期：1998-05-08 00:00:00
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journal_title：European journal of pharmacology
pub_type： 杂志文章
doi：10.1016/0014-2999(90)90604-5
更新日期：1990-05-03 00:00:00
abstract：:Previous examinations demonstrated antidystonic effects of the synaptic vesicle protein 2A (SV2A) ligand levetiracetam in the dt(sz) mutant hamster, an animal model of paroxysmal non-kinesiogenic dyskinesia in which dystonic episodes can be induced by stress. In the present study, we examined the effects of the two ne...
journal_title：European journal of pharmacology
pub_type： 杂志文章
doi：10.1016/j.ejphar.2008.10.048
更新日期：2008-12-28 00:00:00
abstract：:Calsequestrin (CASQ) is a major Ca(2+) storage protein within the sarcoplasmic reticulum (SR) of both cardiac and skeletal muscles. CASQ reportedly acts as a Ca(2+) buffer and Ca(2+)-channel regulator through its unique Ca(2+)-dependent oligomerization, maintaining the free Ca(2+) concentration at a low level (0.5-1mM...
journal_title：European journal of pharmacology
pub_type： 杂志文章
doi：10.1016/j.ejphar.2010.08.001
更新日期：2010-11-10 00:00:00
abstract：:In voltage-clamp experiments with the myelinated nerve fibre of Xenopus laevis, 9-amino-1,2,3,4-tetrahydroacridine (THA) decreased both Na+ and K+ currents and shifted the steady state inactivation potential curve in a negative direction. The effects may be described as (a) a decrease of the permeability constant PNa,...
journal_title：European journal of pharmacology
pub_type： 杂志文章
doi：10.1016/0014-2999(89)90272-0
更新日期：1989-05-30 00:00:00
abstract：:Antagonists, but not agonists, of the 5-HT3 receptor are useful therapeutic agents, and it is possible that partial agonists may also be potentially useful in the clinic. Here we show that 5-fluorotryptamine (5-FT) is a partial agonist at both 5-HT3A and 5-HT3AB receptors with an Rmax (Imax/Imax 5-HT) of 0.64 and 0.45...
journal_title：European journal of pharmacology
pub_type： 杂志文章
doi：10.1016/j.ejphar.2007.11.014
更新日期：2008-02-12 00:00:00
abstract：:The effect of diazoxide, verapamil and compound D600 on calcium and isoproterenol dose-response relationships was investigated in isolated rabbit atrial preparations. All three agents shifted calcium dose-force relationships parallel and to the right. D600 acted as a competitive antagonist of calcium, as a plot of log...
journal_title：European journal of pharmacology
pub_type： 杂志文章
doi：10.1016/0014-2999(77)90009-7
更新日期：1977-10-01 00:00:00
abstract：:Stretch-evoked ATP release from the bladder mucosa is a key event in signaling bladder fullness. Our aim was to examine whether acid and capsaicin can also release ATP and to determine the receptors involved, using agonists and antagonists at TRPV1 and acid-sensing ion channels (ASICs). Strips of porcine bladder mucos...
journal_title：European journal of pharmacology
pub_type： 杂志文章
doi：10.1016/j.ejphar.2012.02.041
更新日期：2012-05-15 00:00:00
abstract：:The ability of angiotensin II (A II) and 5-hydroxytryptamine (5-HT) to depolarise the rat isolated nodose ganglion preparation was examined. 5-HT depolarised the nodose ganglion, both at room temperature (20-24 degrees C) and at 35-37 degrees C. However, A II depolarised the nodose ganglion only under the latter condi...
journal_title：European journal of pharmacology
pub_type： 杂志文章
doi：10.1016/0014-2999(90)90217-t
更新日期：1990-08-21 00:00:00
abstract：:This report describes the molecular pharmacological properties of LR-B/081 (methyl 2-[[4-butyl-2-methyl-6-oxo-5-[[2'-(1H-tetrazol-5- yl) [1,1'-biphenyl]-4-yl]methyl]-1 (6H)-pyrimidinyl]methyl]- 3-thiophenecarboxilate), a novel non-peptide angiotensin II receptor antagonist. This compound potently displaced [3H]angiote...
journal_title：European journal of pharmacology
pub_type： 杂志文章
doi：10.1016/0922-4106(95)90028-4
更新日期：1995-07-18 00:00:00
abstract：:It was previously shown that haloperidol, but not clozapine, induced intense rat catalepsy when co-administered with delta-9-tetrahydrocannabinol. The present study investigated whether similar alterations could be observed on striatal c-Fos immunoreactivity after administration of the same drug combinations. Western ...
journal_title：European journal of pharmacology
pub_type： 杂志文章
doi：10.1016/j.ejphar.2008.08.020
更新日期：2008-11-19 00:00:00
abstract：:Soluble amyloid β-protein (Aβ) oligomers are primary mediators of synaptic dysfunction associated with the progression of Alzheimer's disease. Such Aβ oligomers exist dependent on their rates of aggregation and metabolism. Use of selective somatostatin receptor-subtype agonists have been identified as a potential mean...
journal_title：European journal of pharmacology
pub_type： 杂志文章
doi：10.1016/j.ejphar.2012.03.020
更新日期：2012-05-15 00:00:00
abstract：:Pieces of rat brain incubated in oxygenated Tyrode solution were stimulated with the divalent cation ionophore A 23187. Incubation media were assayed for leukotriene (LT) C4-like immunoreactivity as well as for prostaglandin (PG) D2, 6-keto-PGF1 alpha and thromboxane (TX) B2 using specific and sensitive radioimmunoass...
journal_title：European journal of pharmacology
pub_type： 杂志文章
doi：10.1016/0014-2999(84)90431-x
更新日期：1984-03-16 00:00:00
abstract：:It has been shown that analgesics such as morphine, lidocaine and clonidine increase the release of spinal acetylcholine. Acetylcholine may therefore play an important role in the regulation of spinal pain threshold. Since behavioral as well as in vitro studies have shown a clear involvement of GABA (gamma-amino butyr...
journal_title：European journal of pharmacology
pub_type： 杂志文章
doi：10.1016/j.ejphar.2005.08.035
更新日期：2005-11-21 00:00:00
abstract：:A single dose of 50 mg chlorimipramine was followed by a rapid and pronounced decrease in [3H]imipramine binding to platelet membranes. Incubation of human platelets or platelet membranes with 25 nM chlorimipramine similarly reduced [3H]imipramine binding. Imipramine, desmethylchlorimipramine, chlorpromazine and some ...
journal_title：European journal of pharmacology
pub_type： 杂志文章
doi：10.1016/0014-2999(86)90753-3
更新日期：1986-07-15 00:00:00
abstract：:Binding of the radioligand [125I]iodoclonazepam to three different areas of rat brain (cerebellum, hippocampus and striatum) has been characterised. In all three regions binding is rapid, saturable and of high affinity (cerebellum Bmax = 1.49 +/- 0.3 pmol/mg of protein, Kd = 0.39 +/- 0.06 nM; hippocampus Bmax = 1.5 +/...
journal_title：European journal of pharmacology
pub_type： 杂志文章
doi：10.1016/0014-2999(91)90484-8
更新日期：1991-04-03 00:00:00
abstract：:The pharmacology of neurogenic trigeminovascular vasodilator responses in the dura mater is of interest for understanding the pathophysiology of migraine and to develop new therapies for this disabling common condition. Aminergic mechanisms have been implicated in migraine through direct study of amines in patients, a...
journal_title：European journal of pharmacology
pub_type： 杂志文章
doi：10.1016/s0014-2999(01)01111-6
更新日期：2001-07-13 00:00:00
abstract：:Earlier studies demonstrated that cytokine production is under the tonic control of noradrenaline. As the level and/or the duration of noradrenaline action is regulated by the noradrenaline transporter (NET), which is also a target of antidepressant treatment, we studied its role in the regulation of the cytokine resp...
journal_title：European journal of pharmacology
pub_type： 杂志文章
doi：10.1016/s0014-2999(03)01721-7
更新日期：2003-05-23 00:00:00
abstract：:Insulin resistance is a major pathophysiological feature in the development of type 2 diabetes. The liver is an important organ responsible for the development of insulin resistance, and exploring liver glucose metabolism is important to study insulin resistance. We first established the model of insulin resistance in...
journal_title：European journal of pharmacology
pub_type： 杂志文章
doi：10.1016/j.ejphar.2018.11.024
更新日期：2019-01-15 00:00:00
abstract：:Hyperphosphatemia is a mineral bone-disease that increases cardiovascular complications and all-cause mortality in chronic kidney disease (CKD) patients. Oral phosphate binders absorb the dietary phosphate to prevent its high plasma levels. Moreover, they can adsorb some uremic toxins and decrease inflammation. A few ...
journal_title：European journal of pharmacology
pub_type： 杂志文章,评审
doi：10.1016/j.ejphar.2019.172892
更新日期：2020-02-05 00:00:00
abstract：:Indoline derivatives functions as an inhibitors of epidermal growth factor receptor (EGFR) with the anticancer potential against various cancers. We aim to investigate anti-breast cancer effects and mechanism of action of novel indoline derivatives. Molecular docking of seven indoline derivates with EGFR revealed, N-(...
journal_title：European journal of pharmacology
pub_type： 杂志文章
doi：10.1016/j.ejphar.2020.173195
更新日期：2020-08-15 00:00:00
abstract：:Previous studies from this laboratory suggested that two subtypes of substance P receptor may exist, based on the observations that substance P and related peptides did not exhibit complete cross-desensitisation on guinea-pig ileum, and that two distinct rank orders of potency of tachykinins were observed in various t...
journal_title：European journal of pharmacology
pub_type： 杂志文章
doi：10.1016/0014-2999(83)90052-3
更新日期：1983-01-28 00:00:00
abstract：:The highly toxic monomer 12-deoxyphorbol 13-palmitate (G) was extracted from the roots of Euphorbia fischeriana. Our experimental data confirmed studies showing that 12-deoxyphorbol 13-palmitate had certain antitumor activities. The MTT method, soft agar experiments, and nude mouse tumor experiments proved that 12-deo...
journal_title：European journal of pharmacology
pub_type： 杂志文章
doi：10.1016/j.ejphar.2012.11.015
更新日期：2013-01-30 00:00:00
