abstract：:Unlike the majority of G protein-coupled receptors, the prostaglandin E(2) (PGE(2)) E-prostanoid 3 (EP3) receptor binds agonist with high affinity that is insensitive to the presence of guanosine 5[prime]-O-(3-thio)triphosphate (GTPγS). We report the identification of mutations that confer GTPγS sensitivity to agonist...

journal_title：Molecular pharmacology

authors： Natarajan C,Hata AN,Hamm HE,Zent R,Breyer RM

更新日期：2013-01-01 00:00:00

abstract：:Iron is a biologically essential metal, but excess iron can cause damage to the cardiovascular and nervous systems. We examined the effects of extracellular Fe²⁺ on permeation and gating of Ca(V)3.1 channels stably transfected in HEK293 cells, by using whole-cell recording. Precautions were taken to maintain iron in t...

journal_title：Molecular pharmacology

authors： Lopin KV,Gray IP,Obejero-Paz CA,Thévenod F,Jones SW

更新日期：2012-12-01 00:00:00

abstract：:Previous studies showed that lapatinib and obatoclax interact in a greater-than-additive fashion to cause cell death and do so through a toxic form of autophagy. The present studies sought to extend our analyses. Lapatinib and obatoclax killed multiple tumor cell types, and cells lacking phosphatase and tensin homolog...

journal_title：Molecular pharmacology

authors： Cruickshanks N,Tang Y,Booth L,Hamed H,Grant S,Dent P

更新日期：2012-12-01 00:00:00

abstract：:High-throughput screening has led to the identification of small-molecule blockers of the cystic fibrosis transmembrane conductance regulator (CFTR) chloride channel, but the structural basis of blocker binding remains to be defined. We developed molecular models of the CFTR channel on the basis of homology to the bac...

journal_title：Molecular pharmacology

authors： Norimatsu Y,Ivetac A,Alexander C,O'Donnell N,Frye L,Sansom MS,Dawson DC

更新日期：2012-12-01 00:00:00

abstract：:Identifying novel mechanisms to enhance glucagon-like peptide-1 (GLP-1) receptor signaling may enable nascent medicinal chemistry strategies with the aim of developing new orally available therapeutic agents for the treatment of type 2 diabetes mellitus. Therefore, we tested the hypothesis that selectively modulating ...

journal_title：Molecular pharmacology

authors： Willard FS,Wootten D,Showalter AD,Savage EE,Ficorilli J,Farb TB,Bokvist K,Alsina-Fernandez J,Furness SG,Christopoulos A,Sexton PM,Sloop KW

更新日期：2012-12-01 00:00:00

abstract：:α-Conotoxins are subtype-selective nicotinic acetylcholine receptor (nAChR) antagonists. Although potent α3β2 nAChR-selective α-conotoxins have been identified, currently characterized α-conotoxins show no or only weak affinity for α4β2 nAChRs, which are, besides α7 receptors, the most abundant nAChRs in the mammalian...

journal_title：Molecular pharmacology

authors： Beissner M,Dutertre S,Schemm R,Danker T,Sporning A,Grubmüller H,Nicke A

更新日期：2012-10-01 00:00:00

abstract：:Previously we demonstrated that aldehyde dehydrogenase (ALDH) 1a1 is the major ALDH expressed in mouse liver and is an effective catalyst in metabolism of lipid aldehydes. Quantitative real-time polymerase chain reaction analysis revealed a ≈2.5- to 3-fold induction of the hepatic ALDH1A1 mRNA in mice administered eit...

journal_title：Molecular pharmacology

authors： Makia NL,Amunom I,Falkner KC,Conklin DJ,Surapureddi S,Goldstein JA,Prough RA

更新日期：2012-10-01 00:00:00

abstract：:We investigated the interactions of the anticancer drug vinorelbine with drug efflux transporters and cytochrome P450 3A drug-metabolizing enzymes. Vinorelbine was transported by human multidrug-resistance associated protein (MRP) 2, and Mrp2 knockout mice displayed increased vinorelbine plasma exposure after oral adm...

journal_title：Molecular pharmacology

authors： Lagas JS,Damen CW,van Waterschoot RA,Iusuf D,Beijnen JH,Schinkel AH

更新日期：2012-10-01 00:00:00

abstract：:P2X receptors are trimeric membrane proteins. When they bind extracellular ATP, a conformational change occurs that opens a transmembrane ion channel. The ATP-binding pocket is formed in a cleft between two subunits, and a critical amino acid residue for ATP contact is Lys⁶⁹ (P2X2 numbering). In the present work, we s...

journal_title：Molecular pharmacology

authors： Stelmashenko O,Lalo U,Yang Y,Bragg L,North RA,Compan V

更新日期：2012-10-01 00:00:00

abstract：:Mutations that inhibit Kv11.1 ion channel activity contribute to abnormalities of cardiac repolarization that can lead to long QT2 (LQT2) cardiac arrhythmias and sudden death. However, for most of these mutations, nothing is known about the molecular mechanism linking Kv11.1 malfunction to cardiac death. We have previ...

journal_title：Molecular pharmacology

authors： Donovan AJ,Lansu K,Williams JG,Denning MF,Gentile S

更新日期：2012-09-01 00:00:00

abstract：:The CYP2C genes are extensively regulated at the transcriptional stage. The present study shows for the first time that CYP2Cs are also regulated post-transcriptionally by microRNAs (miRNAs). By using online search engines, we found potential miRNA response elements (MREs) in the 3'-untranslated region (3'-UTR) of the...

journal_title：Molecular pharmacology

authors： Zhang SY,Surapureddi S,Coulter S,Ferguson SS,Goldstein JA

更新日期：2012-09-01 00:00:00

abstract：:Glioma cells with stem cell properties, termed glioma stem-like cells (GSCs), have been linked to tumor formation, maintenance, and progression and are responsible for the failure of chemotherapy and radiotherapy. Because conventional glioma treatments often fail to eliminate GSCs completely, residual surviving GSCs a...

journal_title：Molecular pharmacology

authors： Kim RK,Kim MJ,Yoon CH,Lim EJ,Yoo KC,Lee GH,Kim YH,Kim H,Jin YB,Lee YJ,Cho CG,Oh YS,Gye MC,Suh Y,Lee SJ

更新日期：2012-09-01 00:00:00

abstract：:We reported previously the formation of a glutathionyl conjugate of the active metabolite (AM) of clopidogrel and the covalent modification of a cysteinyl residue of human cytochrome P450 2B6 in a reconstituted system (Mol Pharmacol 80:839-847, 2011). In this work, we extended our studies of the metabolism of clopidog...

journal_title：Molecular pharmacology

authors： Zhang H,Lau WC,Hollenberg PF

更新日期：2012-08-01 00:00:00

abstract：:Drug-induced plasticity of excitatory synapses has been proposed to be the cellular mechanism underlying the aberrant learning associated with addiction. Exposure to various drugs of abuse causes both morphological plasticity of dendritic spines and functional plasticity of excitatory synaptic transmission. Chronic ac...

journal_title：Molecular pharmacology

authors： Miller EC,Zhang L,Dummer BW,Cariveau DR,Loh H,Law PY,Liao D

更新日期：2012-08-01 00:00:00

abstract：:In this study, we investigated the effects of single alanine substitutions of amino acid residues in the supposed ATP binding site of the human P2X3 receptor on the agonistic effect of nucleotide analogs. The wild-type and mutant receptors were expressed in HEK293 cells, and the nucleotide effects were measured by mea...

journal_title：Molecular pharmacology

authors： Riedel T,Wiese S,Leichsenring A,Illes P

更新日期：2012-07-01 00:00:00

abstract：:The X-ray structure of the bacterial sodium channel NavAb provides a new template for the study of sodium and calcium channels. Unlike potassium channels, NavAb contains P2 helices in the outer-pore region. Because the sequence similarity between eukaryotic and prokaryotic sodium channels in this region is poor, the s...

journal_title：Molecular pharmacology

authors： Tikhonov DB,Zhorov BS

更新日期：2012-07-01 00:00:00

abstract：:G-protein-coupled receptor activation is generally analyzed under equilibrium conditions. However, real-life receptor functions are often dependent on very short, transient stimuli that may not allow the achievement of a steady state. This is particularly true for synaptic receptors such as the α(2A)-adrenergic recept...

journal_title：Molecular pharmacology

authors： Ambrosio M,Lohse MJ

更新日期：2012-06-01 00:00:00

abstract：:In cervical cancer, the p53 and retinoblastoma (pRb) tumor suppressor pathways are disrupted by the human papilloma virus (HPV) E6 and E7 oncoproteins, because E6 targets p53 and E7 targets pRb for rapid proteasome-mediated degradation. We have investigated whether E6 suppression with small interfering RNA (siRNA) res...

journal_title：Molecular pharmacology

authors： Tan S,Hougardy BM,Meersma GJ,Schaap B,de Vries EG,van der Zee AG,de Jong S

更新日期：2012-05-01 00:00:00

abstract：:Camptothecin (CPT) is an effective chemotherapeutic agent for treatment of patients with cancer. The mechanisms underlying CPT-mediated responses in cancer cells are not fully understood. MicroRNA (miRNA) play important roles in tumorigenesis and drug sensitivity. However, the interaction between camptothecin and miRN...

journal_title：Molecular pharmacology

authors： Zeng CW,Zhang XJ,Lin KY,Ye H,Feng SY,Zhang H,Chen YQ

更新日期：2012-04-01 00:00:00

abstract：:Bioassay-guided fractionation was used to isolate the lignan polygamain as the microtubule-active constituent in the crude extract of the Mountain torchwood, Amyris madrensis. Similar to the effects of the crude plant extract, polygamain caused dose-dependent loss of cellular microtubules and the formation of aberrant...

journal_title：Molecular pharmacology

authors： Hartley RM,Peng J,Fest GA,Dakshanamurthy S,Frantz DE,Brown ML,Mooberry SL

更新日期：2012-03-01 00:00:00

abstract：:Membrane trafficking of the δ-opioid receptor (DOR) from intracellular compartments to plasma membrane in central neurons, induced by various pathological conditions such as long-term opioid exposure, represents unique receptor plasticity involved in the mechanisms of long-term opioid effects in opioid addiction and o...

journal_title：Molecular pharmacology

authors： Zhang Z,Pan ZZ

更新日期：2012-03-01 00:00:00

abstract：:Aldosterone synthase (AS) regulates blood volume by synthesizing the mineralocorticoid aldosterone. Overproduction of aldosterone in the adrenal gland can lead to hypertension, a major cause of heart disease and stroke. Aldosterone production depends upon stimulation of AS expression by the renin-angiotensin system, w...

journal_title：Molecular pharmacology

authors： Adams BP,Bose HS

更新日期：2012-03-01 00:00:00

abstract：:The phosphorylation of μ-opioid receptors (MOPRs) by G protein-coupled receptor kinases (GRKs), followed by arrestin binding, is thought to be a key pathway leading to desensitization and internalization. The present study used the combination of intracellular and whole-cell recordings from rats and mice, as well as l...

journal_title：Molecular pharmacology

authors： Arttamangkul S,Lau EK,Lu HW,Williams JT

更新日期：2012-03-01 00:00:00

abstract：:The vitamin D receptor (VDR) mediates vitamin D signaling in numerous physiological and pharmacological processes, including bone and calcium metabolism, cellular growth and differentiation, immunity, and cardiovascular function. Although transcriptional regulation by VDR has been investigated intensively, an understa...

journal_title：Molecular pharmacology

authors： Choi M,Yamada S,Makishima M

更新日期：2011-12-01 00:00:00

abstract：:Although α7 nicotinic acetylcholine receptors are considered potentially important therapeutic targets, the development of selective agonists has been stymied by the α7 receptor's intrinsically low probability of opening (P(open)) and the concern that an agonist-based therapeutic approach would disrupt endogenous chol...

journal_title：Molecular pharmacology

authors： Williams DK,Wang J,Papke RL

更新日期：2011-12-01 00:00:00

abstract：:Ethanol (ETOH) can cause apoptotic death of neurons by depleting GSH with an associated increase in oxidative stress. The current study illustrates a means to overcome this ETOH-induced neurotoxicity by enhancing GSH through boosting Nrf2, a transcription factor that controls GSH homeostasis. ETOH treatment caused a s...

journal_title：Molecular pharmacology

authors： Narasimhan M,Mahimainathan L,Rathinam ML,Riar AK,Henderson GI

更新日期：2011-12-01 00:00:00

abstract：:Guanidine and its alkyl analogs stimulate the neuromuscular junction presynaptically by inhibiting voltage-gated potassium (Kv) channels, leading to enhanced release of acetylcholine in the synaptic cleft. This stimulatory effect of guanidine underlies its use in the therapy for the neuromuscular diseases myasthenic s...

journal_title：Molecular pharmacology

authors： Kalia J,Swartz KJ

更新日期：2011-12-01 00:00:00

abstract：:Receptors from distant species may have conserved functions despite significant differences in protein sequences. Whereas the noncritical residues are often changed in distant species, the amino acids critical in receptor functions are often conserved. Studying the conserved residues between receptors from distant spe...

journal_title：Molecular pharmacology

authors： Kuei C,Yu J,Zhu J,Wu J,Zhang L,Shih A,Mirzadegan T,Lovenberg T,Liu C

更新日期：2011-11-01 00:00:00

abstract：:The compound 4-(5-(4-bromophenyl)-3-(6-methyl-2-oxo-4-phenyl-1,2-dihydroquinolin-3-yl)-4,5-dihydro-1H-pyrazol-1-yl)-4-oxobutanoic acid (DQP-1105) is a representative member of a new class of N-methyl-d-aspartate (NMDA) receptor antagonists. DQP-1105 inhibited GluN2C- and GluN2D-containing receptors with IC(50) values ...

journal_title：Molecular pharmacology

authors： Acker TM,Yuan H,Hansen KB,Vance KM,Ogden KK,Jensen HS,Burger PB,Mullasseril P,Snyder JP,Liotta DC,Traynelis SF

更新日期：2011-11-01 00:00:00

abstract：:Two different mechanisms leading to increased current have been described for the small-molecule human ether-à-go-go-related gene (herg) activator NS1643 [1,3-bis-(2-hydroxy-5-trifluoromethylphenyl)-urea]. On herg1a channels expressed in Xenopus laevis oocytes, it mainly acts via attenuation of inactivation and for ra...

journal_title：Molecular pharmacology

authors： Schuster AM,Glassmeier G,Bauer CK

更新日期：2011-11-01 00:00:00

abstract：:MicroRNAs (miRNAs) have emerged as a novel class of endogenous, small, noncoding RNAs that negatively regulate gene expression via degradation or translational inhibition of their target mRNAs. Over 700 miRNAs have been identified and sequenced in humans, and the number of miRNA genes is estimated at more than 1000. I...

journal_title：Molecular pharmacology

authors： Kukreja RC,Yin C,Salloum FN

更新日期：2011-10-01 00:00:00

abstract：:The glucagon-like peptide-1 receptor (GLP-1R) is a key physiological regulator of insulin secretion and a major therapeutic target for the treatment of type II diabetes. However, regulation of GLP-1R function is complex with multiple endogenous peptides that interact with the receptor, including full-length (1-37) and...

journal_title：Molecular pharmacology

authors： Koole C,Wootten D,Simms J,Valant C,Miller LJ,Christopoulos A,Sexton PM

更新日期：2011-09-01 00:00:00

abstract：:All-trans-retinoic acid (atRA) is the active metabolite of vitamin A. atRA is also used as a drug, and synthetic atRA analogs and inhibitors of retinoic acid (RA) metabolism have been developed. The hepatic clearance of atRA is mediated primarily by CYP26A1, but design of CYP26A1 inhibitors is hindered by lack of info...

journal_title：Molecular pharmacology

authors： Thatcher JE,Buttrick B,Shaffer SA,Shimshoni JA,Goodlett DR,Nelson WL,Isoherranen N

更新日期：2011-08-01 00:00:00

abstract：:Notch-1 (Notch) is a cell surface receptor that regulates cell-fate decisions in the developing nervous system, and it may also have roles in synaptic plasticity in the adult brain. Binding of its ligands results in the proteolytic cleavage of Notch by the γ-secretase enzyme complex, thereby causing the release of a N...

journal_title：Molecular pharmacology

authors： Arumugam TV,Cheng YL,Choi Y,Choi YH,Yang S,Yun YK,Park JS,Yang DK,Thundyil J,Gelderblom M,Karamyan VT,Tang SC,Chan SL,Magnus T,Sobey CG,Jo DG

更新日期：2011-07-01 00:00:00

abstract：:Poly(ADP-ribose) polymerase-1 (PARP-1) is a NAD-consuming enzyme with an emerging key role in epigenetic regulation of gene transcription. Although PARP-1 expression is characteristically restricted to the nucleus, a few studies report the mitochondrial localization of the enzyme and its ability to regulate organelle ...

journal_title：Molecular pharmacology

authors： Lapucci A,Pittelli M,Rapizzi E,Felici R,Moroni F,Chiarugi A

更新日期：2011-06-01 00:00:00

abstract：:Microglial activation is an invariant feature of Alzheimer's disease (AD). It is noteworthy that cannabinoids are neuroprotective by preventing β-amyloid (Aβ)-induced microglial activation both in vitro and in vivo. On the other hand, the phytocannabinoid cannabidiol (CBD) has shown anti-inflammatory properties in dif...

journal_title：Molecular pharmacology

authors： Martín-Moreno AM,Reigada D,Ramírez BG,Mechoulam R,Innamorato N,Cuadrado A,de Ceballos ML

更新日期：2011-06-01 00:00:00

abstract：:Mouse embryonic spinal cord neurons in culture exhibit spontaneous calcium oscillations from day in vitro (DIV) 6 through DIV 10. Such spontaneous activity in developing spinal cord contributes to maturation of synapses and development of pattern-generating circuits. Here we demonstrate that these calcium oscillations...

journal_title：Molecular pharmacology

authors： Kelamangalath L,Dravid SM,George J,Aldrich JV,Murray TF

更新日期：2011-06-01 00:00:00

abstract：:To identify novel factors or mechanisms that are important for the resistance of tissues to chemical toxicity, we have determined the mechanisms underlying the previously observed increases in resistance to acetaminophen (APAP) toxicity in the lateral nasal gland (LNG) of the male Cyp2g1-null/Cyp2a5-low mouse. Initial...

journal_title：Molecular pharmacology

authors： Zhou X,Wei Y,Xie F,Laukaitis CM,Karn RC,Kluetzman K,Gu J,Zhang QY,Roberts DW,Ding X

更新日期：2011-04-01 00:00:00

abstract：:Amitriptyline is a classic tricyclic antidepressant (TCA) and has been used to treat the depression and anxiety of patients with cancer, but its relevance to cancer cell apoptosis is not known. In the present study, we demonstrated that amitriptyline inhibited cyclin D2 transactivation and displayed potential antimyel...

journal_title：Molecular pharmacology

authors： Mao X,Hou T,Cao B,Wang W,Li Z,Chen S,Fei M,Hurren R,Gronda M,Wu D,Trudel S,Schimmer AD

更新日期：2011-04-01 00:00:00

abstract：:Herein we provide evidence for the coexpression of two distinct prostacyclin (PGI(2)) receptors (IP) on BEAS-2B human airway epithelial cells. IP receptor heterogeneity initially was suggested by the finding that the rank orders of potency of PGI(2) and three structurally similar analogs [taprostene, iloprost, 15-deox...

journal_title：Molecular pharmacology

authors： Wilson SM,Sheddan NA,Newton R,Giembycz MA

更新日期：2011-03-01 00:00:00