解剖学和形态学
麻醉学
听力与言语-语言病理学
行为科学
心脏和心血管系统
细胞和组织工程学
临床神经病学
危重症监护医学
牙科,口腔外科和医学
皮肤病学
急诊医学
内分泌学和新陈代谢
肠胃学和肝脏学
老人病学和老年医学
卫生保健科学和服务
血液学
免疫学
传染病
综合和补充性医学
医学伦理学
医学信息学
医学实验室技术
医学,全科和内科
医学,法律
医学,研究和试验
神经系统科学
护理
营养学和饮食学
产科医学和妇科医学
肿瘤学
眼科学
整形外科学
耳鼻喉科学
病理学
儿科学
周围血管疾病
药理学和药剂学
生理学
基本医疗保健
精神病学
公共、环境和职业卫生
放射学,核医学和医学成像
康复学
生殖生物学
呼吸系统
风湿病学
运动科学
外科学
毒理学
热带医学
泌尿学和肾脏学
病毒学
老年医学
健康政策和服务
心理学,临床
abstract::For several GPCRs, discrimination between agonism and antagonism is possible on the basis of thermodynamics parameters, such as binding enthalpy and entropy. In this study, we analyze whether agonists and antagonists can also be discriminated thermodynamically at the histamine H(1) receptor (H(1)R). Because previous s...
journal_title:Molecular pharmacology
pub_type: 杂志文章
doi:10.1124/mol.109.055384
更新日期:2009-07-01 00:00:00
abstract::S-Adenosylmethionine (SAMe) and its metabolite 5'-methylthioadenosine (MTA) inhibit mitogen-induced proliferative response in liver and colon cancer cells. SAMe and MTA are also proapoptotic in liver cancer cells by selectively inducing Bcl-x(S) expression. The aims of this work were to assess whether these agents are...
journal_title:Molecular pharmacology
pub_type: 杂志文章
doi:10.1124/mol.108.054411
更新日期:2009-07-01 00:00:00
abstract::The cannabinoid field is currently an active research area. Anandamide (AEA) and 2-arachidonoylglycerol (2-AG) are the most characterized endogenous cannabinoids (also known as endocannabinoids). These neuromodulators have been implicated in various physiologically relevant phenomena, including mood (Witkin et al., 20...
journal_title:Molecular pharmacology
pub_type: 杂志文章,评审
doi:10.1124/mol.109.055251
更新日期:2009-07-01 00:00:00
abstract::Many progestins have been developed for use in contraception, menopausal hormone therapy, and treatment of gynecological diseases. They are derived from either progesterone or testosterone, and they act by binding to the progesterone receptor (PR), a hormone-inducible transcription factor belonging to the nuclear rece...
journal_title:Molecular pharmacology
pub_type: 杂志文章
doi:10.1124/mol.108.054312
更新日期:2009-06-01 00:00:00
abstract::Multidrug and toxin extrusion 1 (MATE1/SLC47A1) is important for excretion of organic cations in the kidney and liver, where it is located on the luminal side. Although its functional and regulatory characteristics have been clarified, its pharmacokinetic roles in vivo have yet to be elucidated. In the present study, ...
journal_title:Molecular pharmacology
pub_type: 杂志文章
doi:10.1124/mol.109.056242
更新日期:2009-06-01 00:00:00
abstract::The deletion of Phe-508 (DeltaPhe508) constitutes the most prevalent of a number of mutations in the cystic fibrosis transmembrane conductance regulator (CFTR) that cause cystic fibrosis (CF). This mutation leads to CFTR misfolding and retention in the endoplasmic reticulum, as well as impaired channel activity. The b...
journal_title:Molecular pharmacology
pub_type: 杂志文章
doi:10.1124/mol.109.055608
更新日期:2009-06-01 00:00:00
abstract::Depending on their primary structure, the 28 mammalian transient receptor potential (TRP) cation channels identified so far can be sorted into 6 subfamilies: TRPC ("Canonical"), TRPV ("Vanilloid"), TRPM ("Melastatin"), TRPP ("Polycystin"), TRPML ("Mucolipin"), and TRPA ("Ankyrin"). The TRPV subfamily (vanilloid recept...
journal_title:Molecular pharmacology
pub_type: 杂志文章,评审
doi:10.1124/mol.109.055624
更新日期:2009-06-01 00:00:00
abstract::The presence of DNA damage initiates signaling through the ataxia-telangiectasia mutated kinase (ATM) and the ATM- and the Rad3-related kinase (ATR), which phosphorylate, thus activating, the checkpoint kinases (Chk) 1 and 2, which leads to cell cycle arrest. The bifunctional DNA alkylator 1,3-bis(2-chloroethyl)-1-nit...
journal_title:Molecular pharmacology
pub_type: 杂志文章
doi:10.1124/mol.108.053124
更新日期:2009-06-01 00:00:00
abstract::Cardiac function is regulated by many hormones and neurotransmitters that exert their physiological effects through the activation of G protein-coupled receptors (GPCRs). Identification of new GPCRs that might display a specific pattern of expression within the heart and differentially regulate specific cardiac functi...
journal_title:Molecular pharmacology
pub_type: 杂志文章
doi:10.1124/mol.108.054155
更新日期:2009-05-01 00:00:00
abstract::Multidrug resistance-associated protein 1 (Mrp1; Abcc1) is expressed in sarcolemma of murine heart, where it probably protects the cardiomyocyte by mediating efflux of endo- and xenobiotics. We used doxorubicin (DOX), a chemotherapeutic drug known to induce oxidative stress and thereby cardiac injury, as a model cardi...
journal_title:Molecular pharmacology
pub_type: 杂志文章
doi:10.1124/mol.108.052209
更新日期:2009-05-01 00:00:00
abstract::Two structural models have been developed to explain how agonist binding leads to ionotropic glutamate receptor (iGluR) activation. At alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) iGluRs, full and partial agonists close the agonist-binding domain (ABD) to different degrees whereas agonist-induced do...
journal_title:Molecular pharmacology
pub_type: 杂志文章
doi:10.1124/mol.108.054254
更新日期:2009-05-01 00:00:00
abstract::Anaplastic thyroid carcinoma (ATC) is among the most aggressive malignancies known and is characterized with rapid growth, early invasion, and complete refractoriness to current therapies. Here we report that triptolide, a small molecule from a Chinese herb, could potently inhibit proliferation in vitro, angiogenesis ...
journal_title:Molecular pharmacology
pub_type: 杂志文章
doi:10.1124/mol.108.052605
更新日期:2009-04-01 00:00:00
abstract::Neuroactive steroids are efficacious potentiators of GABA-A receptors. Recent work has identified a site in the alpha1 subunit of the GABA-A receptor, that is essential for potentiation by steroids. However, each receptor contains two copies of the alpha1 subunit. We generated concatemers of subunits so that the alpha...
journal_title:Molecular pharmacology
pub_type: 杂志文章
doi:10.1124/mol.108.053629
更新日期:2009-04-01 00:00:00
abstract::A recently developed stable isotope dilution liquid chromatography-multiple reaction/mass spectrometry method to quantify focal adhesion kinase (FAK) activation loop phosphorylation was used to study endogenous Src kinase activity. This revealed that bis-phosphorylated pTyr(576)/Tyr(577)-FAK was a biomarker of Src act...
journal_title:Molecular pharmacology
pub_type: 杂志文章
doi:10.1124/mol.108.052464
更新日期:2009-03-01 00:00:00
abstract::Previous studies revealed that phenylhistamines and histaprodifens possess higher potency and affinity at guinea pig histamine H(1)-receptor (gpH(1)R) than at human histamine H(1)-receptor (hH(1)R). However, we recently identified an imidazolylpropylguanidine [N(1)-(3-cyclohexylbutanoyl)-N(2)-[3-(1H-imidazol-4-yl)-pro...
journal_title:Molecular pharmacology
pub_type: 杂志文章
doi:10.1124/mol.108.053009
更新日期:2009-03-01 00:00:00
abstract::Psoralen plus UVA light (PUVA) is commonly used to treat psoriasis, a common skin disorder associated with rapid proliferation of cells. PUVA exerts its antiproliferative activity through formation of DNA monoadducts and interstrand cross-links (ICLs). However, this treatment may lead to skin malignancies as a direct ...
journal_title:Molecular pharmacology
pub_type: 杂志文章
doi:10.1124/mol.108.051698
更新日期:2009-03-01 00:00:00
abstract::The aim of the current study is to determine whether butein (3,4,2',4'-tetrahydroxychalcone) exhibits antiproliferative effects against tumor cells through suppression of the signal transducer and activator of transcription 3 (STAT3) activation pathway. We investigated the effects of butein on constitutive and inducib...
journal_title:Molecular pharmacology
pub_type: 杂志文章
doi:10.1124/mol.108.052548
更新日期:2009-03-01 00:00:00
abstract::Prostate cancer is a highly heterogenous disease in which a patient-tailored care program is much desired. Central to this goal is the development of novel targeted pharmacological interventions. To develop these treatment strategies, an understanding of the integration of cellular pathways involved in both tumorigene...
journal_title:Molecular pharmacology
pub_type: 杂志文章,评审
doi:10.1124/mol.108.053066
更新日期:2009-03-01 00:00:00
abstract::Several lines of evidence suggest that G-protein-coupled receptors can adopt different active conformations, but their direct demonstration in intact cells is still missing. Using a fluorescence resonance energy transfer (FRET)-based approach we studied conformational changes in alpha(2A)-adrenergic receptors in intac...
journal_title:Molecular pharmacology
pub_type: 杂志文章
doi:10.1124/mol.108.052399
更新日期:2009-03-01 00:00:00
abstract::The mammalian copper transporter 1 (CTR1) is responsible for the uptake of copper from the extracellular space. In this study, we used an isogenic pair of CTR1(+/+) and CTR1(-/-) mouse embryo fibroblasts to examine the contribution of CTR1 to the influx of cisplatin (DDP), carboplatin (CBDCA), oxaliplatin (L-OHP), and...
journal_title:Molecular pharmacology
pub_type: 杂志文章
doi:10.1124/mol.108.052381
更新日期:2009-02-01 00:00:00
abstract::We have studied the molecular mechanism by which the nuclear xenobiotic receptors pregnane X receptor (PXR) and constitutive active/androstane receptor (CAR) regulate transcription of the vitamin D(3) 24-hydroxylase (CYP24A1) gene. In the absence of vitamin D(3), PXR activates the CYP24A1 gene by directly binding to a...
journal_title:Molecular pharmacology
pub_type: 杂志文章
doi:10.1124/mol.108.051904
更新日期:2009-02-01 00:00:00
abstract::Arrestins mediate G protein-coupled receptor desensitization, internalization, and signaling. Dopamine D(2) and D(3) receptors have similar structures but distinct characteristics of interaction with arrestins. The goals of this study were to compare arrestin-binding determinants in D(2) and D(3) receptors other than ...
journal_title:Molecular pharmacology
pub_type: 杂志文章
doi:10.1124/mol.108.050534
更新日期:2009-01-01 00:00:00
abstract::4-Methyl-5-(2-pyrazinyl)-1,2-dithiole-3-thione (oltipraz), a prototype drug candidate containing a 1,2-dithiole-3-thione moiety, has been widely studied as a cancer chemopreventive agent. Oltipraz and other novel 1,2-dithiole-3-thione congeners have the capability to prevent insulin resistance via AMP-activated protei...
journal_title:Molecular pharmacology
pub_type: 杂志文章
doi:10.1124/mol.108.051128
更新日期:2009-01-01 00:00:00
abstract::Voltage-gated sodium (Na(V)1) channels play a critical role in modulating the excitability of sensory neurons, and human genetic evidence points to Na(V)1.7 as an essential contributor to pain signaling. Human loss-of-function mutations in SCN9A, the gene encoding Na(V)1.7, cause channelopathy-associated indifference ...
journal_title:Molecular pharmacology
pub_type: 杂志文章
doi:10.1124/mol.108.047670
更新日期:2008-11-01 00:00:00
abstract::The midbrain periaqueductal gray (PAG) is involved in organizing behavioral responses to threat, stress, and pain. These PAG functions are modulated by cholinergic agents. In the present study, we examined the cholinergic modulation of synaptic transmission in the PAG using whole-cell voltage-clamp recordings from rat...
journal_title:Molecular pharmacology
pub_type: 杂志文章
doi:10.1124/mol.108.045872
更新日期:2008-11-01 00:00:00
abstract::1-[6-[[(17beta)-3-methoxyestra-1,3,5(10)-trien-17-yl]amino]hexyl]-1H-pyrrole-2,5-dione (U73122) is widely used to inhibit phospholipase C (PLC)-mediated signaling, but we and others have also reported a PLC-independent block of Kir3 channels in native cells. To elaborate on this major side effect, we examined the acti...
journal_title:Molecular pharmacology
pub_type: 杂志文章
doi:10.1124/mol.108.047837
更新日期:2008-11-01 00:00:00
abstract::This study identifies signaling pathways activated by the beta(2)-/beta(3)-adrenoceptor (AR) agonist zinterol, the selective beta(3)-AR agonist L755507, and the selective beta(3)-AR antagonist L748337 in CHO-K1 cells expressing human beta(3)-adrenoceptors. Zinterol and L755507 caused a robust concentration-dependent i...
journal_title:Molecular pharmacology
pub_type: 杂志文章
doi:10.1124/mol.108.046979
更新日期:2008-11-01 00:00:00
abstract::Analysis of the distribution of mRNA encoding the serotonin (5-hydroxytryptamine) 5-HT(2A) receptor and the mu opioid peptide receptor in rat brain demonstrated their coexpression in neurons in several distinct regions. These regions included the periaqueductal gray, an area that plays an important role in morphine-in...
journal_title:Molecular pharmacology
pub_type: 杂志文章
doi:10.1124/mol.108.048272
更新日期:2008-11-01 00:00:00
abstract::Multidrug resistance protein (MRP) 4 transports a variety of endogenous and xenobiotic organic anions. MRP4 is widely expressed in the body and specifically localized to the renal apical proximal tubule cell membrane, where it mediates the excretion of these compounds into urine. To characterize the MRP4 substrate-bin...
journal_title:Molecular pharmacology
pub_type: 杂志文章
doi:10.1124/mol.107.043661
更新日期:2008-10-01 00:00:00
abstract::The peroxisome proliferator-activated receptors (PPARs) represent pharmacological target molecules to improve insulin resistance in type 2 diabetes mellitus. Here we assessed a functional connection between pharmacological activation of PPAR and vascular endothelial growth factor (VEGF) expression in keratinocytes and...
journal_title:Molecular pharmacology
pub_type: 杂志文章
doi:10.1124/mol.108.049395
更新日期:2008-10-01 00:00:00
abstract::Very few antagonists have been identified for the human pregnane X receptor (PXR). These molecules may be of use for modulating the effects of therapeutic drugs, which are potent agonists for this receptor (e.g., some anticancer compounds and macrolide antibiotics), with subsequent effects on transcriptional regulatio...
journal_title:Molecular pharmacology
pub_type: 杂志文章
doi:10.1124/mol.108.049437
更新日期:2008-09-01 00:00:00
abstract::The phosphatidylcholine-using phospholipase D (PLD) isoform PLD2 is widely expressed in mammalian cells and is activated in response to a variety of promitogenic agonists. In this study, active and inactive hemagglutinin-tagged human PLD2 (HA-PLD2) constructs were stably expressed in an EL4 cell line lacking detectabl...
journal_title:Molecular pharmacology
pub_type: 杂志文章
doi:10.1124/mol.107.040105
更新日期:2008-09-01 00:00:00
abstract::CC and CXC chemokines coinduced in fibroblasts and leukocytes by cytokines and microbial agents determine the number of phagocytes infiltrating into inflamed tissues. Interleukin-8/CXCL8 and stromal cell-derived factor-1/CXCL12 significantly and dose-dependently increased the migration of monocytes, expressing the cor...
journal_title:Molecular pharmacology
pub_type: 杂志文章
doi:10.1124/mol.108.045146
更新日期:2008-08-01 00:00:00
abstract::Nicotine can enhance working memory and attention. Activation of both alpha7 and beta2(*) nicotinic acetylcholine receptors (nAChRs) in the prefrontal cortex (PFC) has been implicated in these processes. The ability of presynaptic nAChRs to modulate neurotransmitter release, notably glutamate release, is postulated to...
journal_title:Molecular pharmacology
pub_type: 杂志文章
doi:10.1124/mol.108.046623
更新日期:2008-08-01 00:00:00
abstract::The precise mechanism by which the cellular uptake of the endocannabinoid anandamide (AEA) occurs has been the source of much debate. In the current study, we show that neuronal differentiated CAD (dCAD) cells accumulate anandamide by a process that is inhibited in a dose-dependent manner by N-(4-hydroxyphenyl)arachid...
journal_title:Molecular pharmacology
pub_type: 杂志文章
doi:10.1124/mol.108.044834
更新日期:2008-07-01 00:00:00
abstract::Dietary lipids and fat-soluble micronutrients are solubilized in mixed micelles and absorbed in the small intestine. Based on an assumption that cholesterol and other fat-soluble molecules share a number of transport mechanisms and the fact that Niemann-Pick C1-like 1 (NPC1L1) is critical for intestinal cholesterol ab...
journal_title:Molecular pharmacology
pub_type: 杂志文章
doi:10.1124/mol.107.043034
更新日期:2008-07-01 00:00:00
abstract::Iron-loading diseases remain an important problem because of the toxicity of iron-catalyzed redox reactions. Iron loading occurs in the mitochondria of Friedreich's ataxia (FA) patients and may play a role in its pathogenesis. This suggests that iron chelation therapy could be useful. We developed previously the lipop...
journal_title:Molecular pharmacology
pub_type: 杂志文章
doi:10.1124/mol.108.046847
更新日期:2008-07-01 00:00:00
abstract::Nod2 is an intracellular pattern recognition receptor that detects a conserved moiety of bacterial peptidoglycan and subsequently activates proinflammatory signaling pathways. Mutations in Nod2 have been implicated to be linked to inflammatory granulomatous disorders, such as Crohn's disease and Blau syndrome. Many ph...
journal_title:Molecular pharmacology
pub_type: 杂志文章
doi:10.1124/mol.108.046169
更新日期:2008-07-01 00:00:00
abstract::Sazetidine-A has been recently proposed to be a "silent desensitizer" of alpha4beta2 nicotinic acetylcholine receptors (nAChRs), implying that it desensitizes alpha4beta2 nAChRs without first activating them. This unusual pharmacological property of sazetidine-A makes it, potentially, an excellent research tool to dis...
journal_title:Molecular pharmacology
pub_type: 杂志文章
doi:10.1124/mol.108.045104
更新日期:2008-06-01 00:00:00
abstract::Immune-mediated drug hypersensitivity reactions (IDHRs) represent a significant problem due to their unpredictable and severe nature, as well as the lack of understanding of the pathogenesis. Sulfamethoxazole (SMX), a widely used antibiotic, has been used as a model compound to investigate the underlying mechanism of ...
journal_title:Molecular pharmacology
pub_type: 杂志文章
doi:10.1124/mol.107.043273
更新日期:2008-06-01 00:00:00