Evidence for Noncanonical Neurotransmitter Activation: Norepinephrine as a Dopamine D2-Like Receptor Agonist.

abstract：:The human CYP2C9 plays a crucial role in the metabolic clearance of a wide range of clinical therapeutics. The *2 allele is a prevalent genetic variation in CYP2C9 that is found in various populations. A marked reduction of catalytic activity toward many important drug substrates has been demonstrated by CYP2C9*2, whi...

journal_title：Molecular pharmacology

authors： Parikh SJ,Evans CM,Obi JO,Zhang Q,Maekawa K,Glass KC,Shah MB

更新日期：2020-11-01 00:00:00

abstract：:The members of the Cys-loop ligand-gated ion channel (LGIC) gene family play a major role in fast synaptic transmission, and these receptors represent an important class of targets for therapeutic agents. Each member of this gene family is a pentameric complex containing one or more different subunits, and a large num...

journal_title：Molecular pharmacology

authors： White MM

更新日期：2006-02-01 00:00:00

abstract：:Type II DNA topoisomerases are targets of acridine drugs. Nine mutations conferring resistance to acridines were obtained by forced molecular evolution, using methyl N-(4'-(9-acridinylamino)-3-methoxy-phenyl) methane sulfonamide (mAMSA), methyl N-(4'-(9-acridinylamino)-2-methoxy-phenyl) carbamate hydrochloride (mAMCA)...

journal_title：Molecular pharmacology

authors： Leontiou C,Watters GP,Gilroy KL,Heslop P,Cowell IG,Craig K,Lightowlers RN,Lakey JH,Austin CA

更新日期：2007-04-01 00:00:00

abstract：:Previous studies have demonstrated that the quinone group may play an important role in modulating the alkylating activity of quinone alkylating agents. Introduction of a quinone moiety markedly increased the alkylating activity and cytotoxic activity of the model quinone alkylating agents benzoquinone mustard and ben...

journal_title：Molecular pharmacology

authors： Begleiter A,Leith MK,Pan SS

更新日期：1991-09-01 00:00:00

abstract：:Kinetics of the interactions between the neuromuscular blocker alcuronium, the specific muscarinic antagonist N-[methyl-3H] methyl scopolamine ([3H]NMS), and muscarinic receptors were investigated in homogenates of rat heart atria. Two effects of alcuronium on the binding of [3H]NMS could be distinguished. (a) Alcuron...

journal_title：Molecular pharmacology

authors： Proska J,Tucek S

更新日期：1994-04-01 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

authors： Ciccimaro E,Hanks SK,Blair IA

更新日期：2009-03-01 00:00:00

abstract：:The nucleoside analog 5-azacytidine is an archetypical drug for epigenetic cancer therapy, and its clinical effectiveness has been demonstrated in the treatment of myelodysplastic syndromes (MDS) and acute myelogenous leukemia (AML). However, therapy resistance in patients with MDS/AML remains a challenging issue. Mem...

journal_title：Molecular pharmacology

authors： Hummel-Eisenbeiss J,Hascher A,Hals PA,Sandvold ML,Müller-Tidow C,Lyko F,Rius M

更新日期：2013-09-01 00:00:00

abstract：:UDP-glucuronosyltransferase (UGT) 1A1 glucuronidates endogenous metabolites, such as bilirubin, and exogenous substances, and plays a critical role in their detoxification and excretion. In a previous article, we described the phenobarbital response activity to a 290-base pair (bp) distal enhancer sequence (-3499/-321...

journal_title：Molecular pharmacology

authors： Sugatani J,Nishitani S,Yamakawa K,Yoshinari K,Sueyoshi T,Negishi M,Miwa M

更新日期：2005-03-01 00:00:00

abstract：:Cytotoxic effects of quinones are thought to be mediated by redox cycles between quinones and quinols whereby reactive oxygen species are generated. The role of glucuronidation in preventing these toxic redox cycles was investigated by using benzo(a)pyrene-3,6-quinone and isolated rat hepatocytes or Reuber hepatoma ce...

journal_title：Molecular pharmacology

authors： Lilienblum W,Bock-Hennig BS,Bock KW

更新日期：1985-04-01 00:00:00

abstract：:In an attempt to better understand the role of the cyclohexene ring (ring A) in the biochemical and pharmacological properties of anthracyclines related to doxorubicin and daunorubicin, we investigated the effects of introduction of a fluorine atom at position 8 of idarubicin (4-demethoxydaunorubicin) on drug molecula...

journal_title：Molecular pharmacology

authors： Animati F,Arcamone F,Bigioni M,Capranico G,Caserini C,De Cesare M,Lombardi P,Pratesi G,Salvatore C,Supino R,Zunino F

更新日期：1996-09-01 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

authors： Dunn HA,Ferguson SS

更新日期：2015-10-01 00:00:00

abstract：:Thapsigargin is a specific inhibitor of the sarco/endoplasmic reticulum Ca(2+) ATPase of the endoplasmic reticulum. Here, we show that stimulation of human HaCaT keratinocytes with nanomolar concentrations of thapsigargin triggers expression of activating transcription factor (ATF) 3, a basic-region leucin zipper tran...

journal_title：Molecular pharmacology

authors： Spohn D,Rössler OG,Philipp SE,Raubuch M,Kitajima S,Griesemer D,Hoth M,Thiel G

更新日期：2010-11-01 00:00:00

abstract：:Most anticancer drugs have their origin in traditional medicinal plants. We describe here a flavone, 5,3'-dihydroxy-3,6,7,8,4'-pentamethoxyflavone (PMF), from the leaves of the Thai plant Gardenia obtusifolia, that has anti-inflammatory and anticancer potential. Because the nuclear factor-κB (NF-κB) pathway is linked ...

journal_title：Molecular pharmacology

authors： Phromnoi K,Reuter S,Sung B,Prasad S,Kannappan R,Yadav VR,Chanmahasathien W,Limtrakul P,Aggarwal BB

更新日期：2011-02-01 00:00:00

abstract：:The recent molecular cloning of the genes encoding three somatostatin (SRIF) receptor subtypes has allowed for the individual expression of these receptors in mammalian cells and characterization of their respective pharmacological profiles. In the present study, we have investigated the affinities of a battery of SRI...

journal_title：Molecular pharmacology

authors： Raynor K,Murphy WA,Coy DH,Taylor JE,Moreau JP,Yasuda K,Bell GI,Reisine T

更新日期：1993-06-01 00:00:00

abstract：:The cytolytic ionotropic ATP receptor P2X7 has several important roles in immune cell regulation, such as cytokine release, apoptosis, and microbial killing. Although P2X7 receptors are frequently coexpressed with another subtype of P2X receptor, P2X4, they are believed not to form heteromeric assemblies but to functi...

journal_title：Molecular pharmacology

authors： Guo C,Masin M,Qureshi OS,Murrell-Lagnado RD

更新日期：2007-12-01 00:00:00

abstract：:We show here that arsenite (As(3+)) elicits multiple effects on gene control, such as the interruption of cell cycle control by initiating G(2)/M arrest as well as inhibiting the aryl hydrocarbon (Ah) receptor-mediated 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD)-inducible expression of CYP1A1. This raises the question ...

journal_title：Molecular pharmacology

authors： Bonzo JA,Chen S,Galijatovic A,Tukey RH

更新日期：2005-04-01 00:00:00

abstract：:Recent years have witnessed the discovery of novel selective agonists of the M(1) muscarinic acetylcholine (ACh) receptor (mAChR). One mechanism invoked to account for the selectivity of such agents is that they interact with allosteric sites. We investigated the molecular pharmacology of two such agonists, 1-[3-(4-bu...

journal_title：Molecular pharmacology

authors： Avlani VA,Langmead CJ,Guida E,Wood MD,Tehan BG,Herdon HJ,Watson JM,Sexton PM,Christopoulos A

更新日期：2010-07-01 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

authors： Shin SM,Kim SG

更新日期：2009-01-01 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：:Propofol, etomidate, and barbiturate anesthetics are allosteric coagonists at pentameric α1β3γ2 GABAA receptors, modulating channel activation via four biochemically established intersubunit transmembrane pockets. Etomidate selectively occupies the two β+/α- pockets, the barbiturate photolabel R-5-allyl-1-methyl-5-(m-...

journal_title：Molecular pharmacology

authors： Szabo A,Nourmahnad A,Halpin E,Forman SA

更新日期：2019-04-01 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：:The cannabinoid analog abnormal cannabidiol [abn-cbd; (-)-4-(3-3,4-trans-p-menthadien-[1,8]-yl)-olivetol] does not bind to CB(1) or CB(2) receptors, yet it acts as a full agonist in relaxing rat isolated mesenteric artery segments. Vasorelaxation by abn-cbd is endothelium-dependent, pertussis toxin-sensitive, and is i...

journal_title：Molecular pharmacology

authors： Offertáler L,Mo FM,Bátkai S,Liu J,Begg M,Razdan RK,Martin BR,Bukoski RD,Kunos G

更新日期：2003-03-01 00:00:00

abstract：:To study behavior of activated G(alpha)(s) in living cells, green fluorescent protein (GFP) was inserted within the internal amino acid sequence of G(alpha)(s) to generate a G(alpha)(s)-GFP fusion protein. The fusion protein maintained a bright green fluorescence and was identified by immunoblotting with antibodies ag...

journal_title：Molecular pharmacology

authors： Yu JZ,Rasenick MM

更新日期：2002-02-01 00:00:00

abstract：:The present study was conducted to establish a pharmacological method of controlling growth of vascular smooth muscle cells (VSMC) by blocking calcium entry. In cultured rat VSMC, 1 nM platelet-derived growth factor (PDGF) induced a biphasic elevation of cytoplasmic free calcium concentration, ([Ca2+]c). The second su...

journal_title：Molecular pharmacology

authors： Nie L,Mogami H,Kanzaki M,Shibata H,Kojima I

更新日期：1996-10-01 00:00:00

abstract：:The aryl hydrocarbon receptor (AhR) is a transcriptional enhancer that is activated by the binding of 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) and related toxic xenobiotics, as well as some naturally occurring compounds. Ligand binding initiates 1) dissociation of the ligand-bound monomeric AhR from the ligand-unocc...

journal_title：Molecular pharmacology

authors： Henry EC,Rucci G,Gasiewicz TA

更新日期：1994-12-01 00:00:00

abstract：:Increasing evidence implicates apoptosis as a major mechanism of cell death in methamphetamine (METH) neurotoxicity. The involvement of a neuroimmune component in apoptotic cell death after injury or chemical damage suggests that cytokines may play a role in METH effects. In the present study, we examined if the absen...

journal_title：Molecular pharmacology

authors： Ladenheim B,Krasnova IN,Deng X,Oyler JM,Polettini A,Moran TH,Huestis MA,Cadet JL

更新日期：2000-12-01 00:00:00

abstract：:Exposure to hepatitis C virus (HCV) can lead to the development of cirrhosis and hepatocellular carcinoma. To examine the effects of long-term HCV infection on hepatic cytochrome P450 1A1 (CYP1A1) expression and function, we used a human hepatoma cell line expressing the HCV subgenomic replicon (Huh.8) to evaluate CYP...

journal_title：Molecular pharmacology

authors： Anderson GR,Hasan A,Yin H,Qadri I,Quattrochi LC

更新日期：2006-09-01 00:00:00

abstract：:Binding of [3H](d)-N-allylnormetazocine ([3H](d)-NANM) to rat brain membranes is stereospecific, reversible, and saturable (Bmax = 260 fmol/mg of protein) and manifests moderately high affinity (Kd = 20 nM). The rank order of potency among opioidbenzomorphans and phencyclidine (PCP) analogs for competition for [3H](d)...

journal_title：Molecular pharmacology

authors： Itzhak Y,Hiller JM,Simon EJ

更新日期：1985-01-01 00:00:00

abstract：:The cDNAs for the four murine aryl hydrocarbon (Ah) receptor alleles were cloned and sequenced, and the deduced amino acid sequences were compared. The Ahb-1 allele encodes a protein of 805 amino acids, the Ahd and Ahb-2 alleles encode proteins of 848 amino acids, and the Ahb-3 allele encodes a protein of 883 amino ac...

journal_title：Molecular pharmacology

authors： Poland A,Palen D,Glover E

更新日期：1994-11-01 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

authors： Wang Y,Jiang L,Mo X,Lan Y,Yang X,Liu X,Zhang J,Zhu L,Liu J,Wu X

更新日期：2017-09-01 00:00:00