Abstract：
:Levonorgestrel (13beta-ethyl-17alpha-ethynyl-17beta-hydroxy-4-gonen-3-one), a potent contraceptive progestin stimulates growth and proliferation of cultured breast cancer cells through a receptor-mediated mechanism, even though levonorgestrel does not bind to the oestrogen receptor (ER). To assess whether the oestrogen-like effects induced by this synthetic progestin are exerted via its metabolic conversion products, we studied the binding affinity of three A-ring levonorgestrel derivatives to the ER and their capability to transactivate an oestrogen-dependent yeast system co-transfected with the human ER gene and oestrogen responsive elements fused to a beta-galactosidase reporter vector. The results demonstrated that the 3beta,5alpha reduced levonorgestrel derivative and to a lesser extent its 3alpha isomer interact with the oestrogen receptor, with a significantly lower relative binding affinity (2.4% and 0.4%, respectively) than that of oestradiol (100%), while levonorgestrel does not. Both levonorgestrel metabolites were able to activate, in a dose-dependent manner, the beta-galactosidase reporter gene in the yeast expression system, an effect that was precluded by a steroidal antioestrogen. The oestrogenic potency of levonorgestrel metabolites was significantly lower (750-fold) than that of oestradiol. Furthermore, high doses of 3beta,5alpha levonorgestrel (2.5 mg/day/6 days) induced an increase of oestrogen-dependent progestin receptor in the anterior pituitary of castrated rats. The overall data offer a plausible explanation for the weak oestrogenic effects induced by high, non-pharmacological doses of levonorgestrel.
journal_name
Eur J Pharmacoljournal_title
European journal of pharmacologyauthors
Santillán R,Pérez-Palacios G,Reyes M,Damián-Matsumura P,García GA,Grillasca I,Lemus AEdoi
10.1016/s0014-2999(01)01263-8keywords:
subject
Has Abstractpub_date
2001-09-14 00:00:00pages
167-74issue
2eissn
0014-2999issn
1879-0712pii
S0014-2999(01)01263-8journal_volume
427pub_type
杂志文章abstract：:Yawning was recorded from five rhesus monkeys restrained in a chair after i.m. injection of dopaminergic compounds: apomorphine (0.03 mg/kg), quinpirole (0.01 mg/kg), and (-)-3-(3-hydroxyphenyl)-N-(1-propyl)piperidine (1 mg/kg). SKF 38393 or physostigmine produced no yawning. Yawning from apomorphine was blocked by ch...
journal_title：European journal of pharmacology
pub_type： 杂志文章
doi：10.1016/0014-2999(91)90351-p
更新日期：1991-08-29 00:00:00
abstract：:Rhesus monkeys were trained to discriminate saline from an injection of ketamine. In tests of stimulus generalization, phencyclidine (PCP) produced dose-related ketamine-appropriate responding in each monkey. Two monohydroxylated PCP metabolites also produced ketamine-like discriminative effects, although only at cons...
journal_title：European journal of pharmacology
pub_type： 杂志文章
doi：10.1016/0014-2999(82)90520-9
更新日期：1982-08-27 00:00:00
abstract：:The effect of papaverine on the positive inotropic response to isopreqaline and to calcium was studied on the rabbit isolated papillary muscle; theophylline and the calcium antagonistic D600 were used for comparison. The dose-response curve for isoprenaline was shifted to the left by papaverine (3 times 10- minus 6 to...
journal_title：European journal of pharmacology
pub_type： 杂志文章
doi：10.1016/0014-2999(75)90102-8
更新日期：1975-02-01 00:00:00
abstract：:This study was undertaken to define some of the cellular mechanisms of action of serotonin on cerebral vascular muscle. Application of serotonin to cat basilar artery resulted in a dose dependent depolarization and contraction beginning at 10(-8) M. The correlation coefficient relating the degree of force development ...
journal_title：European journal of pharmacology
pub_type： 杂志文章
doi：10.1016/0014-2999(83)90034-1
更新日期：1983-09-16 00:00:00
abstract：:The present study was designed to investigate the antinociception of spirocyclopiperazinium salt compound LXM-10-M (2,4-dimethyl-9-β-m-hydroxyphenylethyl-3-oxo-6, 9-diazaspiro [5.5] undecane chloride) in thermal and chemical pain models, and further to explore the molecular target and potential signal pathway. We asse...
journal_title：European journal of pharmacology
pub_type： 杂志文章
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journal_title：European journal of pharmacology
pub_type： 杂志文章
doi：10.1016/0014-2999(88)90535-3
更新日期：1988-07-14 00:00:00
abstract：:Lung cancer is a disease with increasing morbidity worldwide in recent years. Approaches such as chemotherapy and biological targeting for its treatment are urgently needed. Epithelial-mesenchymal transition (EMT) is an important initiation stage for tumor cells to acquire invasive and metastatic abilities. Increasing...
journal_title：European journal of pharmacology
pub_type： 杂志文章
doi：10.1016/j.ejphar.2019.172630
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abstract：:The mesolimbic dopaminergic innervation is supposed to be involved in the mechanisms of central effects exerted by various classes of psychotropic drugs. Antidepressants have been found to interact with the brain dopaminergic system as well, although the precise central location of this interaction is unknown. Some da...
journal_title：European journal of pharmacology
pub_type： 杂志文章
doi：10.1016/0014-2999(87)90689-3
更新日期：1987-03-31 00:00:00
abstract：:The present study was undertaken to investigate whether gap junctional communication could be involved in morphine-induced antinociceptive response using blockers of the gap junctional channel, carbenoxolone and Gap27. Intrathecal pretreatment with either carbenoxolone or Gap27 caused a dose-dependent attenuation of m...
journal_title：European journal of pharmacology
pub_type： 杂志文章
doi：10.1016/j.ejphar.2006.01.038
更新日期：2006-03-27 00:00:00
abstract：:(-)-Epigallocatechin-3-gallate (EGCG), a main flavanol of green tea, potently suppressed the urokinase-type plasminogen activator (uPA) expression in human fibrosarcoma HT 1080 cells. EGCG induced not only the suppression of the uPA promoter activity but also the destabilization of uPA mRNA. EGCG inhibited the phospho...
journal_title：European journal of pharmacology
pub_type： 杂志文章
doi：10.1016/j.ejphar.2003.12.031
更新日期：2004-03-08 00:00:00
abstract：:The effects of endothelin, a potent endogenous vasoconstrictor peptide, were examined in a range of vascular and non-vascular tissues. At concentrations that cause vasoconstriction in portal vein and aorta, the peptide strongly contracted rat uterus, trachea and vas deferens, but not guinea pig ileum. Nifedipine, a di...
journal_title：European journal of pharmacology
pub_type： 杂志文章
doi：10.1016/0014-2999(89)90716-4
更新日期：1989-06-20 00:00:00
abstract：:Kakkon-to is composed of seven medicinal herbs and exhibited novel antipyretic activity by suppressing interleukin-1alpha production responsive to interferon in a murine intranasal influenza virus infection model. Using this model, antipyretic compounds with such novel biological activities were characterized from the...
journal_title：European journal of pharmacology
pub_type： 杂志文章
doi：10.1016/s0014-2999(98)00121-6
更新日期：1998-05-01 00:00:00
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journal_title：European journal of pharmacology
pub_type： 杂志文章
doi：10.1016/0014-2999(87)90642-x
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journal_title：European journal of pharmacology
pub_type： 杂志文章
doi：10.1016/0922-4106(90)90010-u
更新日期：1990-04-25 00:00:00
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journal_title：European journal of pharmacology
pub_type： 杂志文章
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更新日期：1997-03-19 00:00:00
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journal_title：European journal of pharmacology
pub_type： 杂志文章
doi：10.1016/j.ejphar.2007.08.011
更新日期：2007-12-22 00:00:00
abstract：:Eosinophils and their granular proteins are crucial for combating allergic airway diseases. Eosinophils derived from HL-60 clone 15 (HC15) cells have been established as a feasible alternative cell model for human primary eosinophils. Simvastatin, a cholesterol-lowering agent, has been shown to exhibit anti-inflammato...
journal_title：European journal of pharmacology
pub_type： 杂志文章
doi：10.1016/j.ejphar.2019.05.029
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journal_title：European journal of pharmacology
pub_type： 杂志文章
doi：10.1016/0014-2999(75)90050-3
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abstract：:Dose-response curves for morphine (0.5-20 mg/kg) were obtained in 4 rhesus monkeys performing the discrete trials shock titration task. Naloxone (5-500 microgram/kg) uniformly produced a dose dependent, parallel shift of the morphine dose-response curves to right. Plots for the 4 animals of the Log (dose ratio--1) ver...
journal_title：European journal of pharmacology
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journal_title：European journal of pharmacology
pub_type： 杂志文章
doi：10.1016/j.ejphar.2005.01.042
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journal_title：European journal of pharmacology
pub_type： 杂志文章
doi：10.1016/j.ejphar.2016.10.023
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abstract：:Colorectal cancer (CRC) has become one of the major factors of tumor-related morbidity and mortality in the world because of its poor prognosis and consequences of metastatic spread. Currently, chemoprevention has been considered as a way of preventing cancer who takes advantage of plant phytochemicals and synthetic c...
journal_title：European journal of pharmacology
pub_type： 杂志文章,评审
doi：10.1016/j.ejphar.2020.173588
更新日期：2020-11-15 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：:In this study we aimed to test central administration of CDP-choline on serum ghrelin, leptin, glucose and corticosterone levels in rats. Intracerebroventricular (i.c.v.) 0.5, 1.0 and 2.0 µmol CDP-choline and saline were administered to male Wistar-Albino rats. For the measurement of serum leptin and ghrelin levels, b...
journal_title：European journal of pharmacology
pub_type： 杂志文章
doi：10.1016/j.ejphar.2015.07.014
更新日期：2015-10-05 00:00:00
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journal_title：European journal of pharmacology
pub_type： 杂志文章
doi：10.1016/j.ejphar.2007.10.064
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abstract：:The present study was undertaken to investigate the effects of intracavernosal injections of adrenomedullin, a novel hypotensive peptide, on penile erection in anesthetized cats. Responses to adrenomedullin were compared to those elicited by intracavernosal injection of the control triple-drug combination (1.65 mg pap...
journal_title：European journal of pharmacology
pub_type： 杂志文章
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abstract：:The present study aimed to determine whether nefiracetam, N-(2,6-dimethylphenyl)-2-(2-oxo-1-pyrrolidinyl) acetamide, a cognition enhancer, has an effect on learning and memory function in sustained cerebral ischemia, and whether the effect, if any, may accompany modification of the cholinergic or gamma-aminobutyric ac...
journal_title：European journal of pharmacology
pub_type： 杂志文章
doi：10.1016/s0014-2999(02)02360-9
更新日期：2002-10-18 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：:After recovery from a first intraplantar or intrathoracic stimulation with bradykinin, repeated daily provocation with this peptide resulted in a progressive loss of its ability to cause paw or pleural oedema, reaching 0-20% of the control within seven and four consecutive provocations, respectively. The phenomenon wa...
journal_title：European journal of pharmacology
pub_type： 杂志文章
doi：10.1016/0014-2999(92)90011-r
更新日期：1992-09-10 00:00:00
abstract：:Nucleos(t)ide analogues play pivotal roles as antiviral, cytotoxic or immunosuppressive agents. Here, we review recent reports of nucleoside analogues that exhibit broad-spectrum activity towards multiple life-threatening RNA and DNA viruses. We also present a discussion about nucleoside antimetabolites-approved antin...
journal_title：European journal of pharmacology
pub_type： 杂志文章,评审
doi：10.1016/j.ejphar.2019.172747
更新日期：2019-12-15 00:00:00
