Abstract:
AIM:To develop a robust, cell-based, high-content screening (HCS) assay based on receptor internalization for the identification of novel modulators of the epidermal growth factor receptor (EGFR). METHODS:Agonist-induced receptor internalization is part of the signaling cascade of EGFR. Fluorescent-tagged epidermal growth factor (EGF) was used to visualize the internalized receptor-ligand complex. The fluorescent intracellular spots were detected and measured with an ArrayScan HCS reader. Compounds that can competitively bind to EGFR or interfere with EGFR internalization process would result in a reduced number and intensity of intracellular fluorescent spots. This assay was validated, optimized, and applied to a large-scale screening of a library containing 48,000 synthetic compounds. RESULTS:The competition between fluorescent EGF and unlabeled EGF reveals the IC(50) of unlabeled EGF is approximately 0.2 nmol/L, which is comparable with other published reports. Thirteen compounds with a relatively high degree of interference with EGFR internalization were identified. One of the compounds was proven to be agonist of the EGFR since it induced phosphorylation of the receptor and extracellular signal-regulated protein kinase (ERK). CONCLUSION:This automated, objective, and easy-to-use assay provided abundant information, quantitative results, and demonstrated the potential use of HCS methods in searching membrane receptor modulators.
journal_name
Acta Pharmacol Sinjournal_title
Acta pharmacologica Sinicaauthors
Wang J,Xie Xdoi
10.1111/j.1745-7254.2007.00640.xsubject
Has Abstractpub_date
2007-10-01 00:00:00pages
1698-704issue
10eissn
1671-4083issn
1745-7254journal_volume
28pub_type
杂志文章abstract:AIM:Human umbilical cord blood mesenchymal stem cells (hUCB-MSCs) have been shown to ameliorate cerebral ischemia in animal models. In this study we investigated the effects of hUCB-MSCs on inflammatory responses and neuronal apoptosis during the early stage of focal cerebral ischemia in rabbits. METHODS:Focal cerebra...
journal_title:Acta pharmacologica Sinica
pub_type: 杂志文章
doi:10.1038/aps.2014.9
更新日期:2014-05-01 00:00:00
abstract:AIM:To determine whether ATP-sensitive potassium channels are altered in VSMC from arotas and mesenteric arteries of obese rat, and their association with obesity-triggered increase in blood pressure. METHODS:Obesity was induced by 24 weeks of high-fat diet feeding in male Sprague-Dawley rats. Control rats were fed wi...
journal_title:Acta pharmacologica Sinica
pub_type: 杂志文章
doi:10.1111/j.1745-7254.2008.00810.x
更新日期:2008-10-01 00:00:00
abstract:AIM:To search for novel effective P-glycoprotein (P-gp) reversal agents in the blood-brain barrier (BBB). METHODS:Using rhodamine123 (Rh123) to examine the functional activity of P-gp in cultured bovine brain capillary endothelial cells (BCEC) and screen various principles on P-gp modulation in BBB. RESULTS:All of te...
journal_title:Acta pharmacologica Sinica
pub_type: 杂志文章
doi:
更新日期:2002-07-01 00:00:00
abstract:AIM:To Study the interaction of macrophage colony-stimulating factor (M-CSF) and interleukin-10 (IL-10) in productions of IL-12 and IL-18 and expressions of CD14, CD23, and CD64 by human monocytes. METHODS:Purified adherent human monocytes were cultured with M-CSF or IL-10 alone, or with M-CSF+IL-10 and 2-3d later, th...
journal_title:Acta pharmacologica Sinica
pub_type: 杂志文章
doi:
更新日期:2004-10-01 00:00:00
abstract:AIM:Oral risedronate is effective in the treatment of postmenopausal osteoporosis when administered daily, weekly, or monthly. In this 1-year, randomized, double-blind, multicenter study we compared the weekly 35-mg and daily 5-mg risedronate dosing regimens in the treatment of Chinese postmenopausal women with osteopo...
journal_title:Acta pharmacologica Sinica
pub_type: 杂志文章,多中心研究,随机对照试验
doi:10.1038/aps.2015.30
更新日期:2015-07-01 00:00:00
abstract:AIM:To investigate the mechanism of brain interleukin-1 beta (IL-1 beta) in reserpine-induced behavioral depression in rats. METHODS:Porsult swim test was used in the measurement of depressive behavior and ELISA was used in measurement of brain IL-1 beta. RESULTS:Intraperitoneal injection of reserpine (0, 4, 6, and 8...
journal_title:Acta pharmacologica Sinica
pub_type: 杂志文章
doi:
更新日期:2004-03-01 00:00:00
abstract:AIM:To investigate the effects of onychin on the proliferation of cultured rat artery vascular smooth muscle cells (VSMCs) in the presence of 10% new-born calf serum (NCS). METHODS:Rat VSMCs were incubated with onychin 150 micromol/L or genistein 10 micromol/L in the presence of 10% NCS for 24 h. The proliferation of ...
journal_title:Acta pharmacologica Sinica
pub_type: 杂志文章
doi:10.1111/j.1745-7254.2005.00526.x
更新日期:2005-02-01 00:00:00
abstract::Brain and eye tissues are subject to a reduced version of immune surveillance, which has evolved to protect the particularly sensitive tissues from accidental bystander damage created by regular inflammatory responses. Yet, there are autoimmune diseases in both organs. This review discusses the nature of immune reacti...
journal_title:Acta pharmacologica Sinica
pub_type: 杂志文章,评审
doi:10.1038/aps.2010.149
更新日期:2010-09-01 00:00:00
abstract:AIM:To study the antioxidant, activity of Qizhu Tang (QZT) both in vivo and in vitro. METHODS:QZT consists of 4 herbal constituents (Rhizoma Atractylodis Macrocephalae, Poria cocos, Kadix Notoginseng, and Radix Astragali), each of the components and their combinations were examined in vitro for 1, 1-diphenyl-2-picrylh...
journal_title:Acta pharmacologica Sinica
pub_type: 杂志文章
doi:
更新日期:2000-12-01 00:00:00
abstract:AIM:To determine the role of dietary low histamine on the seizure development of pentylenetetrazol (PTZ)-induced kindling in rats. METHODS:After 14 d of feeding on a low histamine diet (LH, containing 0.145 mumol/g of histamine), the rats were chemically kindled by repeated intraperitoneal injection of a subconvulsant...
journal_title:Acta pharmacologica Sinica
pub_type: 杂志文章
doi:10.1111/j.1745-7254.2005.00097.x
更新日期:2005-04-01 00:00:00
abstract:AIM:To investigate the antidepressant-like effects of a novel 5-HT3 receptor antagonist N-(benzo[d]thiazol-2-yl)-3-methoxyquinoxalin-2-carboxamide (6z) in acute and chronic murine models of depression. METHODS:5-HT3 receptor antagonism was examined in guinea pig ileum in vitro. A tail suspension test (TST) was used as...
journal_title:Acta pharmacologica Sinica
pub_type: 杂志文章
doi:10.1038/aps.2014.89
更新日期:2014-12-01 00:00:00
abstract:AIM:Abrus agglutinin (AGG) from the seeds of Indian medicinal plant Abrus precatorius belongs to the class II ribosome inactivating protein family. In this study we investigated the anticancer effects of AGG against human hepatocellular carcinoma in vitro and in vivo. METHODS:Cell proliferation, DNA fragmentation, Ann...
journal_title:Acta pharmacologica Sinica
pub_type: 杂志文章
doi:10.1038/aps.2014.15
更新日期:2014-06-01 00:00:00
abstract:AIM:To ascertain the effects of erlotinib on CYP3A, to investigate the amplitude and kinetics of erlotinib-mediated inhibition of seven major CYP isoforms in human liver microsomes (HLMs) for evaluating the magnitude of erlotinib in drug-drug interaction in vivo. METHODS:The activities of 7 major CYP isoforms (CYP1A2,...
journal_title:Acta pharmacologica Sinica
pub_type: 杂志文章
doi:10.1038/aps.2010.218
更新日期:2011-03-01 00:00:00
abstract:AIM:To examine how the higher expression level of CYP3A4 isoenzyme influenced the cytotoxicity of the antitumor triazoloacridinone derivative C-1305 in Chinese hamster ovary (CHO) cells. METHODS:Three CHO cell lines were examined: wild-type CHO cells; CHO-HR cells with overexpression of human cytochrome P450 reductase...
journal_title:Acta pharmacologica Sinica
pub_type: 杂志文章
doi:10.1038/aps.2012.132
更新日期:2013-01-01 00:00:00
abstract:AIM:To test the hypothesis that PI3K/Akt/eNOS signaling has a protective role in a murine model of ventilation associated lung injury (VALI) through down-regulation of p38 MAPK signaling. METHODS:Male C57BL/J6 (wild-type, WT) or eNOS knockout mice (eNOS(-/-)) were exposed to mechanical ventilation (MV) with low (LV(T)...
journal_title:Acta pharmacologica Sinica
pub_type: 杂志文章
doi:10.1038/aps.2009.190
更新日期:2010-02-01 00:00:00
abstract:AIM:The pro-fibrogenic cytokine transforming growth factor-beta 1 (TGF-beta1) has attracted much attention for its potential role in the etiology of idiopathic pulmonary fibrosis (IPF). Here, we demonstrate that MS80, a novel sulfated oligosaccharide extracted from seaweed, can bind TGF-beta1. The aim of the present st...
journal_title:Acta pharmacologica Sinica
pub_type: 杂志文章
doi:10.1038/aps.2009.86
更新日期:2009-07-01 00:00:00
abstract::Retinoid X receptor-α (RXRα), a unique member of the nuclear receptor superfamily, represents an intriguing and unusual target for pharmacologic interventions and therapeutic applications in cancer, metabolic disorders and neurodegenerative diseases. Despite the fact that the RXR-based drug Targretin (bexarotene) is c...
journal_title:Acta pharmacologica Sinica
pub_type: 杂志文章,评审
doi:10.1038/aps.2014.109
更新日期:2015-01-01 00:00:00
abstract:AIM:To investigate possible intracellular signal molecules involved in diphenylhydantoin (DPH)-mediated apoptosis of cerebellar granule neurons (CGN) and explore possible molecular mechanisms of neurotoxicity of DPH. METHODS:Fluorescein diacetate (FDA) stain, hochest 33258 stain, and agar gel electrophoresis were used...
journal_title:Acta pharmacologica Sinica
pub_type: 杂志文章
doi:
更新日期:2003-06-01 00:00:00
abstract:AIM:G protein-coupled inwardly rectifying potassium channels (GIRK) are important for neuronal signaling and membrane excitability. In the present study, we intend to find whether GIRK channels express functionally in adult rat dorsal root ganglion (DRG) neurons. METHODS:We used RT-PCR to detect mRNA for 4 subunits of...
journal_title:Acta pharmacologica Sinica
pub_type: 杂志文章
doi:10.1111/j.1745-7254.2007.00478.x
更新日期:2007-02-01 00:00:00
abstract:AIM:Fibroblast growth factor 7 (FGF7) is involved in a number of physiological and pathological processes, including lung disease. However, relatively little is known about the effect of FGF7 gene polymorphisms on chronic obstructive pulmonary disease (COPD) susceptibility. This study aimed to investigate the associati...
journal_title:Acta pharmacologica Sinica
pub_type: 杂志文章
doi:10.1038/aps.2012.69
更新日期:2012-08-01 00:00:00
abstract:AIM:To examine the effects of microinjection of melatonin and its receptor antagonists into the anterior hypothalamic area (AHA) on blood pressure (BP) and heart rate (HR) in normotensive and stress-induced hypertensive rats. METHODS:Melatonin and its receptor antagonists were microinjected into the AHA, then BP, mean...
journal_title:Acta pharmacologica Sinica
pub_type: 杂志文章
doi:
更新日期:2001-11-01 00:00:00
abstract:AIM:To investigate the effects of chronic ethanol intake on the locomotor activity and the levels of calcium/calmodulin-dependent protein kinase IV (CaM kinase IV) in the nucleus accumbens (NAc) of rats. Simultaneously, the effects of nonselective opioid antagonist (naloxone) on the CaM kinase IV expression in the NAc ...
journal_title:Acta pharmacologica Sinica
pub_type: 杂志文章
doi:10.1111/j.1745-7254.2008.00805.x
更新日期:2008-06-01 00:00:00
abstract:AIM:Breviscapine isolated from the Chinese herb Erigeron breviscapus (Vant) Hand-Mazz is widely used to treat cardiovascular and cerebrovascular diseases. The aim of this study was to improve the pharmacokinetic profiles of breviscapine using nanostructured lipid carrier based on an ionic complex formation. METHODS:Br...
journal_title:Acta pharmacologica Sinica
pub_type: 杂志文章
doi:10.1038/aps.2013.43
更新日期:2013-08-01 00:00:00
abstract:AIM:To investigate whether total Panax notoginseng saponins (PNS) could protect endothelium of rabbit iliac artery against balloon endothelial denudation (BED) injury. METHODS:The morphology changes of the endothelium were observed with scanning electron microscope (SEM) and hematoxylin and eosin stain after BED of ra...
journal_title:Acta pharmacologica Sinica
pub_type: 杂志文章
doi:
更新日期:2004-09-01 00:00:00
abstract::Due to the lack of typical clinical symptoms, the average delay time for diagnosis of pulmonary hypertension (PH) is longer than 2 years. It is urgent to find biomarkers for PH diagnosis. In this study we investigated whether plasma microRNAs (miRNAs) can be used as biomarkers for PH diagnosis. We used microarray to i...
journal_title:Acta pharmacologica Sinica
pub_type: 杂志文章
doi:10.1038/aps.2018.39
更新日期:2018-07-01 00:00:00
abstract:AIM:To study the effects of cimetidine (Cim) on the production of interferon gamma (IFN gamma) and tumor necrosis factor alpha (TNF alpha) by splenocytes in immune-derived aplastic anemic (AA) mice. METHODS:Aplastic anemic mice model was constructed first, and then the splenocytes were induced to secrete IFN gamma and...
journal_title:Acta pharmacologica Sinica
pub_type: 杂志文章
doi:
更新日期:2001-03-01 00:00:00
abstract::Estrogens are important endocrine hormones that control physiological functions in reproductive organs, and play a pivotal role in the generation and progression of breast cancer. Therapeutic drugs including anti-estrogen and aromatase inhibitors are used to treat patients with breast cancer. The estrogen receptors, E...
journal_title:Acta pharmacologica Sinica
pub_type: 杂志文章,评审
doi:10.1038/aps.2014.123
更新日期:2015-01-01 00:00:00
abstract:AIM:Based on the structural analysis to reveal the mechanism of ligand binding to beta-secretase and the specificity of each binding sub-site. METHODS:Molecular dynamics was used to simulate on the ligand free beta-secretase and ligand bound beta-secretase. The trajectories were analyzed using the essential dynamics, ...
journal_title:Acta pharmacologica Sinica
pub_type: 杂志文章
doi:
更新日期:2004-06-01 00:00:00
abstract:AIM:To study the effect and mechanism of pyronaridine (PND) on the reversal of multidrug resistance (MDR) in K562/A02 and MCF7/ADR cell lines with mdr1+. METHODS:MTT assay was used to determine the cells growth inhibition after incubation for 72 h in the presence of doxorubicin (DOX) with or without PND. Intracellular...
journal_title:Acta pharmacologica Sinica
pub_type: 杂志文章
doi:
更新日期:2002-06-01 00:00:00
abstract:AIM:To investigate the immunoregulatory functions of water extracts of Hericium erinaceum (WEHE) focusing on natural killer (NK) cell-based anticancer activities. METHODS:Mouse splenocytes or purely isolated NK cells were stimulated with 1-100 mg/L WEHE for 24 h followed by co-culture with (51)Cr-labeled Yac-1 cells f...
journal_title:Acta pharmacologica Sinica
pub_type: 杂志文章
doi:10.1111/j.1745-7254.2007.00577.x
更新日期:2007-06-01 00:00:00