Identification and characterization of a small molecule antagonist of human VPAC(2) receptor.

abstract：:We have observed that rodent cell lines (mouse, hamster) contain approximately 10 times the levels of dihydrofolate reductase as human cell lines, yet the sensitivity to methotrexate (ED(50)), the folate antagonist that targets this enzyme, is similar. Our previous studies showed that dihydrofolate reductase protein l...

journal_title：Molecular pharmacology

authors： Hsieh YC,Skacel NE,Bansal N,Scotto KW,Banerjee D,Bertino JR,Abali EE

更新日期：2009-10-01 00:00:00

abstract：:In vivo administration of the porphyrogenic agent allylisopropylacetamide (AIA) to phenobarbital-pretreated rats results in marked loss of hepatic cytochrome P-450 content. Using isozyme-selective functional markers, we now show that such loss reflects inactivation of several phenobarbital-inducible and constitutive i...

journal_title：Molecular pharmacology

authors： Bornheim LM,Underwood MC,Caldera P,Rettie AE,Trager WF,Wrighton SA,Correia MA

更新日期：1987-08-01 00:00:00

abstract：:Leukotriene B4 (LTB4) induced rapid breakdown of prelabeled inositol phospholipids in rat peritoneal polymorphonuclear leukocytes (PMNs). Formation of [3H]inositol triphosphate ([3H]IP3) was rapid, with a peak of 250-300% of the control level, after 5-15 sec of exposure to LTB4. Accumulation of [3H]inositol bisphospha...

journal_title：Molecular pharmacology

authors： Mong S,Chi-Rosso G,Miller J,Hoffman K,Razgaitis KA,Bender P,Crooke ST

更新日期：1986-09-01 00:00:00

abstract：:We have synthesized and characterized a high-affinity alpha 1-adrenergic receptor probe, 4-amino-6,7-dimethoxy-2[4'- [5"(3"'-125I-iodo-4"'-aminophenyl)pentanoyl]-1'-piperazinyl] quinazoline (125I-A55453). This ligand binds reversibly to rat hepatic plasma membranes with high affinity (KD = 77 +/- 6 pM), and it labels ...

journal_title：Molecular pharmacology

authors： Dickinson KE,Leeb-Lundberg LM,Heald SL,Wikberg JE,DeBernardis JF,Caron MG,Lefkowitz RJ

更新日期：1984-09-01 00:00:00

abstract：:Ca2-dependent protein phosphorylations activated by calmodulin or phospholipid were studied using selective inhibitors. Both protein phosphorylations were inhibited by N-(6-aminohexyl)-5-chloro-1-naphthalenesulfonamide (W-7) and its derivatives. Kinetic analysis indicated that the primary effect of these agents was me...

journal_title：Molecular pharmacology

authors： Tanaka T,Ohmura T,Yamakado T,Hidaka H

更新日期：1982-09-01 00:00:00

abstract：:In rat pancreatic zymogen granules (ZG), an ATP-sensitive K(+) conductance and a Cl(-) conductance have been characterized that are inversely regulated by an approximately 65-kDa multidrug resistance P-glycoprotein (mdr1) gene product. In search of a label for purification of this protein, we found that the dihydropyr...

journal_title：Molecular pharmacology

authors： Braun M,Thévenod F

更新日期：2000-02-01 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

authors： Bolognini D,Tobin AB,Milligan G,Moss CE

更新日期：2016-03-01 00:00:00

abstract：:ATP-gated purinergic receptors (P2XRs) are a family of cation-permeable channels that conduct Ca(2+) and facilitate voltage-sensitive Ca(2+) entry in excitable cells. To study Ca(2+) signaling by P2XRs and its dependence on voltage-sensitive Ca(2+) influx, we expressed eight cloned P2XR subtypes individually in gonado...

journal_title：Molecular pharmacology

authors： Koshimizu TA,Van Goor F,Tomić M,Wong AO,Tanoue A,Tsujimoto G,Stojilkovic SS

更新日期：2000-11-01 00:00:00

abstract：:2-Hydroxy-4(-2,2,3,3,3-pentafluoropropoxy)-benzoic acid (UR-1505), a new molecule chemically related to salicylic acid, has immunomodulator properties and is currently under clinical development for treatment of atopic dermatitis. The present work describes the immunomodulatory profile of UR-1505. UR-1505 targets T ce...

journal_title：Molecular pharmacology

authors： Román J,de Arriba AF,Barrón S,Michelena P,Giral M,Merlos M,Bailón E,Comalada M,Gálvez J,Zarzuelo A,Ramis I

更新日期：2007-08-01 00:00:00

abstract：:In light of the potential use of the thiazolidinedione family of peroxisome proliferator-activated receptor-gamma (PPARgamma) agonists in prostate cancer treatment, this study assessed the mechanism by which these agents suppress prostate-specific antigen (PSA) secretion in prostate cancer cells. Two lines of evidence...

journal_title：Molecular pharmacology

authors： Yang CC,Ku CY,Wei S,Shiau CW,Chen CS,Pinzone JJ,Ringel MD,Chen CS

更新日期：2006-05-01 00:00:00

abstract：:The Integrated Stress Response (ISR) is a signaling program that enables cellular adaptation to stressful conditions like hypoxia and nutrient deprivation in the tumor microenvironment. An important effector of the ISR is activating transcription factor 4 (ATF4), a transcription factor that regulates genes involved in...

journal_title：Molecular pharmacology

authors： Sayers CM,Papandreou I,Guttmann DM,Maas NL,Diehl JA,Witze ES,Koong AC,Koumenis C

更新日期：2013-03-01 00:00:00

abstract：:Cultured murine hepatoma 1c1c7 cells were treated with either the actin filament-disrupting drug cytochalasin D or the microtubule inhibitors colchicine and nocadazole (NOC) to assess the role of the cytoskeleton in the process of cytochrome P450 Cyp1a-1 induction. Indirect fluorescence analyses demonstrated that micr...

journal_title：Molecular pharmacology

authors： Schöller A,Hong NJ,Bischer P,Reiners JJ Jr

更新日期：1994-05-01 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：:Dysfunction of p53 and resistance to cancer drugs can arise through mutually exclusive overexpression of MDM2 or MDM4. Cisplatin-resistant cells, however, can demonstrate increased binding of both MDM2 and MDM4 to p53 but in absence of cellular overexpression. Whether MDM2 inhibitors alone can activate p53 in these re...

journal_title：Molecular pharmacology

authors： Xie X,He G,Siddik ZH

更新日期：2020-04-01 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

authors： Tsuda M,Terada T,Mizuno T,Katsura T,Shimakura J,Inui K

更新日期：2009-06-01 00:00:00

abstract：:The class III antiarrhythmic drugs amiodarone and bretylium tosylate are cationic/amphiphilic, and various substances with these physico-chemical properties are known to directly activate heterotrimeric regulatory G proteins. We asked the question of whether class III antiarrhythmic drugs are also direct G protein act...

journal_title：Molecular pharmacology

authors： Hagelüken A,Nürnberg B,Harhammer R,Grünbaum L,Schunack W,Seifert R

更新日期：1995-02-01 00:00:00

abstract：:The ligand specificity of rat adenohypophyseal vasopressin receptors was directly compared to that of peripheral receptors of the V1 and V2 types. For this purpose a series of 15 recently designed vasopressin antagonists was used. The affinities of these antagonists for rat adenohypophyseal membranes were deduced from...

journal_title：Molecular pharmacology

authors： Jard S,Gaillard RC,Guillon G,Marie J,Schoenenberg P,Muller AF,Manning M,Sawyer WH

更新日期：1986-08-01 00:00:00

abstract：:The effects of ethanol on a number of electrophysiological parameters were examined in 10 different voltage-gated potassium channels expressed in Xenopus oocytes. None of the channels examined was highly sensitive to ethanol, but there was significant variability among the channels tested at concentrations of ethanol ...

journal_title：Molecular pharmacology

authors： Anantharam V,Bayley H,Wilson A,Treistman SN

更新日期：1992-09-01 00:00:00

abstract：:Polyamides are a class of synthetic molecules that exhibit high-affinity, sequence-specific reversible binding in the DNA minor groove but are incapable of inducing DNA damage. In cell-free systems, polyamides have been shown to regulate gene expression by activation, repression, and antirepression. However, effective...

journal_title：Molecular pharmacology

authors： Philips BJ,Chang AY,Dervan PB,Beerman TA

更新日期：2005-03-01 00:00:00

abstract：:The human histamine H(4)-receptor (hH(4)R) possesses high constitutive activity and, like the human H(1)-receptor (hH(1)R), is involved in the pathogenesis of type-I allergic reactions. The study aims were to explore the value of dual H(1)/H(4)R antagonists as antiallergy drugs and to address the question of whether H...

journal_title：Molecular pharmacology

authors： Deml KF,Beermann S,Neumann D,Strasser A,Seifert R

更新日期：2009-11-01 00:00:00

abstract：:The ligand-binding sites of many G protein-coupled receptors (GPCRs) are situated around and deeply embedded within the central pocket formed by their seven transmembrane-spanning α-helical domains. Generally, these binding sites are assumed accessible to endogenous ligands from the aqueous phase. Recent advances in t...

journal_title：Molecular pharmacology

authors： Szlenk CT,Gc JB,Natesan S

更新日期：2019-11-01 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：: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

authors： Lan H,Liu Y,Bell MI,Gurevich VV,Neve KA

更新日期：2009-01-01 00:00:00

abstract：:The new olivacine derivative S16020-2 (NSC-659687) is a DNA topoisomerase II inhibitor endowed with a remarkable antitumor activity against various experimental tumors. In vitro physicochemical properties of this compound, in particular its interaction with DNA and DNA topoisomerase II, were very similar to those of e...

journal_title：Molecular pharmacology

authors： Le Mée S,Chaminade F,Delaporte C,Markovits J,Saucier JM,Jacquemin-Sablon A

更新日期：2000-10-01 00:00:00

abstract：:The current study was designed to investigate the importance of cationic amino acid transporters (CATs) for the L-arginine supply to nitric oxide (NO) synthases in mouse J774A.1 macrophages and human EA.hy926 endothelial cells. CAT-1 was expressed in both cell types, whereas CAT-2B was only expressed in activated macr...

journal_title：Molecular pharmacology

authors： Closs EI,Scheld JS,Sharafi M,Förstermann U

更新日期：2000-01-01 00:00:00

abstract：:Sulfation is an important pathway in the biotransformation of many drugs, xenobiotic compounds, neurotransmitters, and hormones. The sulfate donor for these reactions is 3'-phosphoadenosine-5'-phosphosulfate (PAPS). We set out to determine whether PAPS might serve as a photoaffinity ligand for sulfotransferase enzymes...

journal_title：Molecular pharmacology

authors： Otterness DM,Powers SP,Miller LJ,Weinshilboum RM

更新日期：1991-01-01 00:00:00

abstract：:Our laboratory recently isolated and sequenced cDNAs encoding the microsomal flavin-containing monooxygenases (FMOs) from rabbit liver and rabbit lung. As a first step in understanding the molecular bases for the catalytic and physical differences between these enzymes, we have expressed them in COS-1 cells and compar...

journal_title：Molecular pharmacology

authors： Lawton MP,Kronbach T,Johnson EF,Philpot RM

更新日期：1991-11-01 00:00:00

abstract：:To investigate the roles of individual transmembrane segments (TM) of the human D3 dopamine receptor in its ligand-receptor interactions, we generated chimeric receptors in which its TMs were replaced, one at a time, partially or entirely, by the corresponding TM of the homologous human D1 receptor. Ligand binding pro...

journal_title：Molecular pharmacology

authors： Alberts GL,Pregenzer JF,Im WB

更新日期：1998-08-01 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：: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