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
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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::It is widely accepted that cAMP signaling is compartmentalized within cells. However, our knowledge of how receptors, cAMP signaling enzymes, effectors, and other key proteins form specific signaling complexes to regulate specific cell responses is limited. The multicomponent nature of these systems and the spatiotemp...
journal_title:Molecular pharmacology
pub_type: 杂志文章,评审
doi:10.1124/mol.117.110825
更新日期:2018-04-01 00:00:00
abstract::Acute desensitization of mu opioid receptors is thought to be an initial step in the development of tolerance to opioids. Given the resistance of the respiratory system to develop tolerance, desensitization of neurons in the Kölliker-Fuse (KF), a key area in the respiratory circuit, was examined. The activation of G p...
journal_title:Molecular pharmacology
pub_type: 杂志文章
doi:10.1124/mol.117.109603
更新日期:2018-01-01 00:00:00
abstract::The chemotherapeutic anthracycline metabolite doxorubicinol (doxOL) has been shown to interact with and disrupt the function of the cardiac ryanodine receptor Ca2+ release channel (RyR2) in the sarcoplasmic reticulum (SR) membrane and the SR Ca2+ binding protein calsequestrin 2 (CSQ2). Normal increases in RyR2 activit...
journal_title:Molecular pharmacology
pub_type: 杂志文章
doi:10.1124/mol.117.108183
更新日期:2017-11-01 00:00:00
abstract::The bile salt export pump (BSEP/ABCB11) transports bile salts from hepatocytes into bile canaliculi. Its malfunction is associated with severe liver disease. One reason for functional impairment of BSEP is systemic administration of drugs, which as a side effect inhibit the transporter. Therefore, drug candidates are ...
journal_title:Molecular pharmacology
pub_type: 杂志文章
doi:10.1124/mol.117.108688
更新日期:2017-10-01 00:00:00
abstract::Intermediate-conductance (KCa3.1) and small-conductance (KCa2) calcium-activated K+ channels are gated by calcium binding to calmodulin (CaM) molecules associated with the calmodulin-binding domain (CaM-BD) of these channels. The existing KCa activators, such as naphtho[1,2-d]thiazol-2-ylamine (SKA-31), 6,7-dichloro-1...
journal_title:Molecular pharmacology
pub_type: 杂志文章
doi:10.1124/mol.117.109421
更新日期:2017-10-01 00:00:00
abstract::Smad4, a key transcription factor in the transforming growth factor-β signaling pathway, is involved in a variety of cell physiologic and pathologic processes. Here, we characterized megakaryocyte/platelet-specific Smad4 deficiency in mice to elucidate its effect on platelet function. We found that megakaryocyte/plate...
journal_title:Molecular pharmacology
pub_type: 杂志文章
doi:10.1124/mol.116.107417
更新日期:2017-09-01 00:00:00
abstract::Interleukin 6 (IL-6), which is elevated in patients with congestive heart failure and acts as both a chronic marker of inflammation and an acute-phase reactant, is associated with myocardial damage. Circulating levels of arginine vasopressin (AVP) are elevated during cardiac stress and could be a factor for cardiac in...
journal_title:Molecular pharmacology
pub_type: 杂志文章
doi:10.1124/mol.116.107698
更新日期:2017-09-01 00:00:00
abstract::Seven transmembrane G protein-coupled receptors (GPCRs) are often phosphorylated at the C terminus and on intracellular loops in response to various extracellular stimuli. Phosphorylation of GPCRs by GPCR kinases and certain other kinases can promote the recruitment of arrestin molecules. The arrestins critically regu...
journal_title:Molecular pharmacology
pub_type: 杂志文章,评审
doi:10.1124/mol.116.107839
更新日期:2017-09-01 00:00:00
abstract::G protein-coupled receptors (GPCRs) and receptor tyrosine kinases (RTKs) act in concert to regulate cell growth, proliferation, survival, and migration. Metabotropic GABAB receptor (GABABR) is the GPCR for the main inhibitory neurotransmitter GABA in the central nervous system. Increased expression of GABABR has been ...
journal_title:Molecular pharmacology
pub_type: 杂志文章
doi:10.1124/mol.116.107854
更新日期:2017-09-01 00:00:00
abstract::CYP3A4 is one of the major drug-metabolizing enzymes in human and is responsible for the metabolism of 60% of clinically used drugs. Many drugs are able to induce the expression of CYP3A4, which usually causes drug-drug interactions and adverse drug reactions. This study aims to explore the role of histone modificatio...
journal_title:Molecular pharmacology
pub_type: 杂志文章
doi:10.1124/mol.117.108225
更新日期:2017-08-01 00:00:00
abstract::Small-molecule restoration of wild-type structure and function to mutant p53 (so-called mutant reactivation) is a highly sought-after goal in cancer drug development. We previously discovered that small-molecule zinc chelators called zinc metallochaperones (ZMCs) reactivate mutant p53 by restoring zinc binding to zinc...
journal_title:Molecular pharmacology
pub_type: 杂志文章
doi:10.1124/mol.116.107409
更新日期:2017-06-01 00:00:00
abstract::Tumor necrosis factor α (TNFα) plays a vital role in cancer progression as it is associated with inflammation and promotion of cancer angiogenesis and metastasis. The effects of TNFα are mediated by its downstream target, the oncogene lysine-rich CEACAM1 coisolated protein (LYRIC, also known as metadherin or astrocyte...
journal_title:Molecular pharmacology
pub_type: 杂志文章
doi:10.1124/mol.116.107870
更新日期:2017-05-01 00:00:00
abstract::The c-Myc (MYC) transcription factor is a major cancer driver and a well-validated therapeutic target. However, directly targeting MYC has been challenging. Thus, identifying proteins that interact with and regulate MYC may provide alternative strategies to inhibit its oncogenic activity. In this study, we report the ...
journal_title:Molecular pharmacology
pub_type: 杂志文章
doi:10.1124/mol.116.107623
更新日期:2017-04-01 00:00:00
abstract::P-glycoprotein, an ATP-driven efflux pump, regulates permeability of the blood-brain barrier (BBB). Sphingolipids, endogenous to brain tissue, influence inflammatory responses and cell survival in vitro. Our laboratory has previously shown that sphingolipid signaling by sphingosine 1-phosphate decreases basal P-glycop...
journal_title:Molecular pharmacology
pub_type: 杂志文章
doi:10.1124/mol.116.107169
更新日期:2017-04-01 00:00:00
abstract::The intermediate-conductance Ca2+-activated K+ channel (KCa3.1) constitutes an attractive pharmacological target for immunosuppression, fibroproliferative disorders, atherosclerosis, and stroke. However, there currently is no available crystal structure of this medically relevant channel that could be used for structu...
journal_title:Molecular pharmacology
pub_type: 杂志文章
doi:10.1124/mol.116.108068
更新日期:2017-04-01 00:00:00
abstract::The isoprenoid donor for protein geranylgeranylation reactions, geranylgeranyl diphosphate (GGDP), is the product of the enzyme GGDP synthase (GGDPS) that condenses farnesyl diphosphate (FDP) and isopentenyl pyrophosphate. GGDPS inhibition is of interest from a therapeutic perspective for multiple myeloma because we h...
journal_title:Molecular pharmacology
pub_type: 杂志文章
doi:10.1124/mol.116.107326
更新日期:2017-03-01 00:00:00
abstract::The ability of chemically distinct ligands to produce different effects on the same G protein-coupled receptor (GPCR) has interesting therapeutic implications, but, if excessively propagated downstream, would introduce biologic noise compromising cognate ligand detection. We asked whether cells have the ability to lim...
journal_title:Molecular pharmacology
pub_type: 杂志文章
doi:10.1124/mol.116.106369
更新日期:2017-02-01 00:00:00
abstract::Past decades of cancer research have mainly focused on the role of various extracellular and intracellular biochemical signals on cancer progression and metastasis. Recent studies suggest an important role of mechanical forces in regulating cellular behaviors. This review first provides an overview of the mechanobiolo...
journal_title:Molecular pharmacology
pub_type: 杂志文章,评审
doi:10.1124/mol.116.106765
更新日期:2016-12-01 00:00:00
abstract::The metabotropic glutamate 5 receptor and the cannabinoid type 1 receptor are G protein-coupled receptors that are widely expressed in the central nervous system. Metabotropic glutamate 5 receptors, present at the postsynaptic site, are coupled to Gαq/11 proteins and display an excitatory response upon activation, whe...
journal_title:Molecular pharmacology
pub_type: 杂志文章,评审
doi:10.1124/mol.116.104372
更新日期:2016-11-01 00:00:00
abstract::Na+-d-glucose cotransporter 1 (SGLT1) is rate-limiting for glucose absorption in the small intestine. Shortly after intake of glucose-rich food, SGLT1 abundance in the luminal membrane of the small intestine is increased. This upregulation occurs via glucose-induced acceleration of the release of SGLT1-containing vesi...
journal_title:Molecular pharmacology
pub_type: 杂志文章
doi:10.1124/mol.116.104521
更新日期:2016-11-01 00:00:00
abstract::Peroxisome proliferator-activated receptor δ (PPARδ) has been implicated in vascular pathophysiology. However, its functions in atherogenic changes of the vascular wall have not been fully elucidated. PPARδ activated by GW501516 (2-[2-methyl-4-[[4-methyl-2-[4-(trifluoromethyl)phenyl]-1,3-thiazol-5-yl]methylsulfanyl]ph...
journal_title:Molecular pharmacology
pub_type: 杂志文章
doi:10.1124/mol.116.104679
更新日期:2016-11-01 00:00:00
abstract::G protein-coupled receptors are sensors that interact with a large variety of elements, including photons, ions, and large proteins. Not surprisingly, these receptors participate in the numerous normal physiologic processes that we refer to as health and in its perturbations that constitute disease. It has been estima...
journal_title:Molecular pharmacology
pub_type:
doi:10.1124/mol.116.106062
更新日期:2016-11-01 00:00:00
abstract::Cytosolic sulfotransferase 1C3 (SULT1C3) is the least characterized of the three human SULT1C subfamily members. Originally identified as an orphan SULT by computational analysis of the human genome, we recently reported that SULT1C3 is expressed in human intestine and LS180 colorectal adenocarcinoma cells and is upre...
journal_title:Molecular pharmacology
pub_type: 杂志文章
doi:10.1124/mol.116.106005
更新日期:2016-11-01 00:00:00
abstract::Eukaryotic cells assemble stress granules (SGs) when translation initiation is inhibited. Different cell signaling pathways regulate SG production. Particularly relevant to this process is 5'-AMP-activated protein kinase (AMPK), which functions as a stress sensor and is transiently activated by adverse physiologic con...
journal_title:Molecular pharmacology
pub_type: 杂志文章
doi:10.1124/mol.116.105494
更新日期:2016-10-01 00:00:00
abstract::The nicotinic acetylcholine receptor (nAChR) belongs to a superfamily of pentameric ligand-gated ion channels involved in many physiologic and pathologic processes. Among nAChRs, receptors comprising the α7 subunit are unique because of their high Ca(2+) permeability and fast desensitization. nAChR agonists elicit a t...
journal_title:Molecular pharmacology
pub_type: 杂志文章,评审
doi:10.1124/mol.116.104240
更新日期:2016-09-01 00:00:00
abstract::The delta family of ionotropic glutamate receptors consists of glutamate delta-1 (GluD1) and glutamate delta-2 receptors. We have previously shown that GluD1 knockout mice exhibit features of developmental delay, including impaired spine pruning and switch in the N-methyl-D-aspartate receptor subunit, which are releva...
journal_title:Molecular pharmacology
pub_type: 杂志文章
doi:10.1124/mol.116.104786
更新日期:2016-08-01 00:00:00
abstract::K201 (JTV-519) may prevent abnormal Ca(2+) leak from the sarcoplasmic reticulum (SR) in the ischemic heart and skeletal muscle (SkM) by stabilizing the ryanodine receptors (RyRs; RyR1 and RyR2, respectively). We tested direct modulation of the SR Ca(2+)-stimulated ATPase (SERCA) and RyRs by K201. In isolated cardiac a...
journal_title:Molecular pharmacology
pub_type: 杂志文章
doi:10.1124/mol.115.102277
更新日期:2016-08-01 00:00:00
abstract::Tetrodotoxin-sensitive Na(+) currents have been extensively studied because they play a major role in neuronal firing and bursting. In this study, we showed that voltage-dependent Na(+) currents are regulated in a slow manner by oxotremorine (oxo-M) and angiotensin II in rat sympathetic neurons. We found that these cu...
journal_title:Molecular pharmacology
pub_type: 杂志文章
doi:10.1124/mol.115.101931
更新日期:2016-04-01 00:00:00
abstract::The Gαi/o-coupled dopamine D2-like receptor family comprises three subtypes: the D2 receptor (D2R), with short and long isoform variants (D2SR and D2LR), D3 receptor (D3R), and D4 receptor (D4R), with several polymorphic variants. The common overlap of norepinephrine innervation and D2-like receptor expression pattern...
journal_title:Molecular pharmacology
pub_type: 杂志文章
doi:10.1124/mol.115.101808
更新日期:2016-04-01 00:00:00
abstract::Despite some blockbuster G protein-coupled receptor (GPCR) drugs, only a small fraction (∼ 15%) of the more than 390 nonodorant GPCRs have been successfully targeted by the pharmaceutical industry. One way that this issue might be addressed is via translation of recent deorphanization programs that have opened the pro...
journal_title:Molecular pharmacology
pub_type: 杂志文章,评审
doi:10.1124/mol.115.102301
更新日期:2016-03-01 00:00:00
abstract::Aldose reductase (AKR1B1) is a critical drug target because of its involvement in diabetic complications, inflammation, and tumorigenesis. However, to date, development of clinically useful inhibitors has been largely unsuccessful. Cyclopentenone prostaglandins (cyPGs) are reactive lipid mediators that bind covalently...
journal_title:Molecular pharmacology
pub_type: 杂志文章
doi:10.1124/mol.115.100693
更新日期:2016-01-01 00:00:00
abstract::[This corrects the article on p. 21 in vol. 81, PMID: 21984254.]. ...
journal_title:Molecular pharmacology
pub_type: 已发布勘误
doi:10.1124/mol.115.075234err
更新日期:2016-01-01 00:00:00
abstract::Human cytochrome P450 (CYP) 2C enzymes metabolize ∼30% of clinically prescribed drugs and various environmental chemicals. CYP2C8, an important member of this subfamily, metabolizes the anticancer drug paclitaxel, certain antidiabetic drugs, and endogenous substrates, including arachidonic acid, to physiologically act...
journal_title:Molecular pharmacology
pub_type: 杂志文章
doi:10.1124/mol.115.100255
更新日期:2016-01-01 00:00:00
abstract::Thymidylate synthase (TYMS; EC 2.1.1.15) catalyzes the reductive methylation of 2'-deoxyuridine-5'-monophosphate (dUMP) by N(5),N(10)-methyhlenetetrahydrofolate, forming dTMP for the maintenance of DNA replication and repair. Inhibitors of TYMS have been widely used in the treatment of neoplastic disease. A number of ...
journal_title:Molecular pharmacology
pub_type: 杂志文章
doi:10.1124/mol.115.099614
更新日期:2015-12-01 00:00:00
abstract::Ligands that selectively inhibit human α3β2 and α6β2 nicotinic acetylcholine receptor (nAChRs) and not the closely related α3β4 and α6β4 subtypes are lacking. Current α-conotoxins (α-Ctxs) that discriminate among these nAChR subtypes in rat fail to discriminate among the human receptor homologs. In this study, we desc...
journal_title:Molecular pharmacology
pub_type: 杂志文章
doi:10.1124/mol.115.100982
更新日期:2015-11-01 00:00:00
abstract::GPR139 is an orphan G-protein-coupled receptor expressed in the central nervous system. To identify its physiologic ligand, we measured GPR139 receptor activity from recombinant cells after treatment with amino acids, orphan ligands, serum, and tissue extracts. GPR139 activity was measured using guanosine 5'-O-(3-[(35...
journal_title:Molecular pharmacology
pub_type: 杂志文章
doi:10.1124/mol.115.100412
更新日期:2015-11-01 00:00:00
abstract::Phosphodiesterase-9 (PDE9) inhibitors have been studied as potential therapeutics for treatment of central nervous system diseases and diabetes. Here, we report the discovery of a new category of PDE9 inhibitors by rational design on the basis of the crystal structures. The best compound, (S)-6-((1-(4-chlorophenyl)eth...
journal_title:Molecular pharmacology
pub_type: 杂志文章
doi:10.1124/mol.115.099747
更新日期:2015-11-01 00:00:00
abstract::G protein-coupled receptors (GPCRs) contribute to the regulation of every aspect of human physiology and are therapeutic targets for the treatment of numerous diseases. As a consequence, understanding the myriad of mechanisms controlling GPCR signaling and trafficking is essential for the development of new pharmacolo...
journal_title:Molecular pharmacology
pub_type: 杂志文章,评审
doi:10.1124/mol.115.098509
更新日期:2015-10-01 00:00:00
abstract::Signaling by G-protein-coupled receptors is often considered a uniform process, whereby a homogeneously activated proportion of randomly distributed receptors are activated under equilibrium conditions and produce homogeneous, steady-state intracellular signals. While this may be the case in some biologic systems, the...
journal_title:Molecular pharmacology
pub_type: 杂志文章,评审
doi:10.1124/mol.115.100248
更新日期:2015-09-01 00:00:00
abstract::In the present study, we have elucidated the functional characteristics and mechanism of action of methaqualone (2-methyl-3-o-tolyl-4(3H)-quinazolinone, Quaalude), an infamous sedative-hypnotic and recreational drug from the 1960s-1970s. Methaqualone was demonstrated to be a positive allosteric modulator at human α1,2...
journal_title:Molecular pharmacology
pub_type: 杂志文章
doi:10.1124/mol.115.099291
更新日期:2015-08-01 00:00:00