abstract：:Anthracyclines are potent anticancer agents, but their use is limited by cardiotoxicity at high cumulative doses. The mechanisms involved in anthracycline-mediated cardiotoxicity are still poorly understood, but numerous investigations have indicated a role for iron in this process. Our previous studies using neoplast...

journal_title：Molecular pharmacology

authors： Kwok JC,Richardson DR

更新日期：2004-01-01 00:00:00

abstract：:Cholinesterase inhibitors are commonly used to improve cognition and treat psychosis and other behavioral symptoms in Alzheimer's disease, Parkinson's disease, and other neuropsychiatric conditions. However, mechanisms may exist that down-regulate the synaptic response to altered cholinergic transmission, thus limitin...

journal_title：Molecular pharmacology

authors： Volpicelli-Daley LA,Hrabovska A,Duysen EG,Ferguson SM,Blakely RD,Lockridge O,Levey AI

更新日期：2003-12-01 00:00:00

abstract：:Previous studies have demonstrated that cotreatment with mitogen activated-protein kinase kinase (MEK) 1/2 inhibitors (e.g., PD184352) and the checkpoint abrogator 7-hydroxystaurosporine (UCN-01) dramatically induces apoptosis in a variety of human leukemia and multiple myeloma cell types. The purpose of this study wa...

journal_title：Molecular pharmacology

authors： Dai Y,Dent P,Grant S

更新日期：2003-12-01 00:00:00

abstract：:The efficacy of antineoplastic compounds can depend heavily on the genetic background of the cells exposed to the drugs. This becomes evident by the fact that HT-29 human colon cancer cells but not primary murine nontransformed colonocytes are efficiently submitted to apoptosis by the flavonoid flavone. By determining...

journal_title：Molecular pharmacology

authors： Wenzel U,Kuntz S,Daniel H

更新日期：2003-12-01 00:00:00

abstract：:Peroxisome proliferator-activated receptors (PPARs) are a family of nuclear receptors that are involved in lipid metabolism, differentiation, proliferation, cell death, and inflammation. Three subtypes have been identified: PPAR-alpha, -delta, and -gamma. We have previously shown presence of PPAR-gamma mRNA in the amn...

journal_title：Molecular pharmacology

authors： Berry EB,Eykholt R,Helliwell RJ,Gilmour RS,Mitchell MD,Marvin KW

更新日期：2003-12-01 00:00:00

abstract：:High expression of the aflatoxin B1 (AFB1)-8,9-epoxide-conjugating glutathione S-transferase A3 (mGSTA3) subunit in mouse liver confers intrinsic resistance to AFB1 hepatocarcinogenesis. It is not known how the gene encoding this protein is regulated. The murine mGSTA3 gene has been identified using bioinformatics. It...

journal_title：Molecular pharmacology

authors： Jowsey IR,Jiang Q,Itoh K,Yamamoto M,Hayes JD

更新日期：2003-11-01 00:00:00

abstract：:Glyceryl trinitrate (GTN) is used in the treatment of angina pectoris and cardiac failure, but the rapid onset of GTN tolerance limits its clinical utility. Research suggests that a principal cause of tolerance is inhibition of an enzyme responsible for the production of physiologically active concentrations of NO fro...

journal_title：Molecular pharmacology

authors： DiFabio J,Ji Y,Vasiliou V,Thatcher GR,Bennett BM

更新日期：2003-11-01 00:00:00

abstract：:Receptors for the serine protease thrombin and for lysophospholipids are coupled to G proteins and control a wide range of cellular functions, including mitogenesis. Activators of these receptors are present in blood, and can enter the brain during central nervous system (CNS) injury. Reactive astrogliosis, a prominen...

journal_title：Molecular pharmacology

authors： Sorensen SD,Nicole O,Peavy RD,Montoya LM,Lee CJ,Murphy TJ,Traynelis SF,Hepler JR

更新日期：2003-11-01 00:00:00

abstract：:Formyl peptide receptor (FPR) and formyl peptide receptor like 1 (FPRL1) play important roles in inflammation and immunity. Stimulation of FPR and FPRL1 initiates a cascade of signaling events, leading to activation of various phagocyte responses, including chemotaxis, superoxide generation, and exocytosis. Trp-Lys-Ty...

journal_title：Molecular pharmacology

authors： Bae YS,Song JY,Kim Y,He R,Ye RD,Kwak JY,Suh PG,Ryu SH

更新日期：2003-10-01 00:00:00

abstract：:Newly synthesized tocainide analogs were tested for their state-dependent affinity and use-dependent behavior on sodium currents (INa) of adult skeletal muscle fibers by means of the Vaseline-gap voltage clamp method. The drugs had the pharmacophore amino group constrained in position alpha [N-(2,6-dimethylphenyl)pyrr...

journal_title：Molecular pharmacology

authors： De Luca A,Talon S,De Bellis M,Desaphy JF,Lentini G,Corbo F,Scilimati A,Franchini C,Tortorella V,Camerino DC

更新日期：2003-10-01 00:00:00

abstract：:The aryl hydrocarbon receptor (AHR) binds planar aromatic compounds and up-regulates the transcription of a battery of xenobiotic-metabolizing enzymes. To identify proteins involved in the biosynthesis of endogenous AHR ligands, we screened extracts of various mouse tissues for AHR signaling activity. We found heart e...

journal_title：Molecular pharmacology

authors： Bittinger MA,Nguyen LP,Bradfield CA

更新日期：2003-09-01 00:00:00

abstract：:Adenosine acting via A2a receptors (A2aR) is a potent cerebral vasodilator that relaxes vascular smooth muscle cells (VSMCs) by a mechanism attributed to activation of cAMP-dependent protein kinase (cAK). We examined effects of adenosine and its mechanism of action on L-type Ca2+ channels in native VSMCs from rat basi...

journal_title：Molecular pharmacology

authors： Murphy K,Gerzanich V,Zhou H,Ivanova S,Dong Y,Hoffman G,West GA,Winn HR,Simard JM

更新日期：2003-09-01 00:00:00

abstract：:Classical chemoattractant receptors are of fundamental importance to immune responses. The two major roles of such receptors are the modulation of chemotaxis and the generation of reactive oxygen species. The formyl peptide receptor-like 1 (FPRL1) can be stimulated by two different ligands, Trp-Lys-Tyr-Met-Val-Met-CON...

journal_title：Molecular pharmacology

authors： Bae YS,Park JC,He R,Ye RD,Kwak JY,Suh PG,Ho Ryu S

更新日期：2003-09-01 00:00:00

abstract：:The therapeutic potential of antitumor drugs is seriously limited by the manifestation of cellular drug resistance. We used the budding yeast Saccharomyces cerevisiae as a model system to identify novel mechanisms of resistance to one of the most active anticancer agents, cisplatin. We pinpointed NPR2 (nitrogen permea...

journal_title：Molecular pharmacology

authors： Schenk PW,Brok M,Boersma AW,Brandsma JA,Den Dulk H,Burger H,Stoter G,Brouwer J,Nooter K

更新日期：2003-08-01 00:00:00

abstract：:The nuclear receptor peroxisome proliferator-activated receptor (PPAR) is activated by a diverse group of acidic ligands, including many peroxisome proliferator chemicals present in the environment. Janus tyrosine kinase-signal transducer and activator of transcription (JAK-STAT) signaling is activated by multiple cyt...

journal_title：Molecular pharmacology

authors： Shipley JM,Waxman DJ

更新日期：2003-08-01 00:00:00

abstract：:The D2 dopamine receptor (D2R) was examined for its ability to mediate nuclear factor-kappaB (NF-kappaB) activation through G proteins. Stimulation of D2R-transfected HeLa cells with its agonist quinpirole induced the expression of a NF-kappaB luciferase reporter and formation of NF-kappaB-DNA complex. This response w...

journal_title：Molecular pharmacology

authors： Yang M,Zhang H,Voyno-Yasenetskaya T,Ye RD

更新日期：2003-08-01 00:00:00

abstract：:Taxanes act by inhibiting microtubule dynamics; in this study, we have investigated mitochondria as an additional target of taxanes. We incubated isolated mitochondria in the presence of taxanes with or without stimulation of the mitochondrial respiratory state. Results showed that they rapidly induced the loss of del...

journal_title：Molecular pharmacology

authors： Ferlini C,Raspaglio G,Mozzetti S,Distefano M,Filippetti F,Martinelli E,Ferrandina G,Gallo D,Ranelletti FO,Scambia G

更新日期：2003-07-01 00:00:00

abstract：:Although ATP-sensitive K+ channels continue to be explored for their therapeutic potential, developments in high-affinity radioligands to investigate native and recombinant KATP channels have been less forthcoming. This study reports the identification and pharmacological characterization of a novel iodinated 1,4-dihy...

journal_title：Molecular pharmacology

authors： Davis-Taber R,Molinari EJ,Altenbach RJ,Whiteaker KL,Shieh CC,Rotert G,Buckner SA,Malysz J,Milicic I,McDermott JS,Gintant GA,Coghlan MJ,Carroll WA,Scott VE,Gopalakrishnan M

更新日期：2003-07-01 00:00:00

abstract：:Extracellular protons inhibit N-methyl-D-aspartate (NMDA) receptors with an IC50 value in the physiological pH range. To identify the molecular determinants of proton sensitivity, we used scanning mutagenesis of the NR1 subunit to search for residues that control proton inhibition of NMDA receptors. Homology modeling ...

journal_title：Molecular pharmacology

authors： Low CM,Lyuboslavsky P,French A,Le P,Wyatte K,Thiel WH,Marchan EM,Igarashi K,Kashiwagi K,Gernert K,Williams K,Traynelis SF,Zheng F

更新日期：2003-06-01 00:00:00

abstract：:The membrane-permeable, noncompetitive inositol 1,4,5-trisphosphate (IP3)-receptor inhibitor 2-aminoethoxydiphenyl borane (2-APB) has been widely used to probe for IP3-receptor involvement in calcium signaling pathways. However, a number of recent studies in different cell types revealed other sites of action of 2-APB...

journal_title：Molecular pharmacology

authors： Braun FJ,Aziz O,Putney JW Jr

更新日期：2003-06-01 00:00:00

abstract：:We determined the effect of flufenamic acid (FFA) and related derivatives on gap junction channel currents, applying the dual whole-cell patch-clamp technique to pairs of N2A neuroblastoma cells transfected with various connexins. FFA reduced gap junction channel currents in a reversible and concentration-dependent ma...

journal_title：Molecular pharmacology

authors： Srinivas M,Spray DC

更新日期：2003-06-01 00:00:00

abstract：:We examined the effects on allosteric modulation and ligand binding of the mutation of amino acid residues of the human A(3) adenosine receptor (A(3)AR) that are hypothesized to be near one of three loci: the putative sodium binding site, the putative ligand binding site, and the DRY motif in transmembrane helical dom...

journal_title：Molecular pharmacology

authors： Gao ZG,Kim SK,Gross AS,Chen A,Blaustein JB,Jacobson KA

更新日期：2003-05-01 00:00:00

abstract：:Telomerase activity is expressed in most types of cancer cells but not in normal somatic cells, suggesting that telomerase may be an important target for cancer chemotherapy. Inhibition of telomerase results in telomere erosion, leading to the subsequent growth arrest of cancer cells followed by senescence or cell dea...

journal_title：Molecular pharmacology

authors： Kim JH,Kim JH,Lee GE,Lee JE,Chung IK

更新日期：2003-05-01 00:00:00

abstract：:Noscapine, a microtubule-interfering agent, has been shown to arrest mitosis, to induce apoptosis, and to have potent antitumor activity. We report herein that two brominated derivatives of noscapine, 5-bromonoscapine (5-Br-nosc) and reduced 5-bromonoscapine (Rd 5-Br-nosc), have higher tubulin binding activity than no...

journal_title：Molecular pharmacology

authors： Zhou J,Gupta K,Aggarwal S,Aneja R,Chandra R,Panda D,Joshi HC

更新日期：2003-04-01 00:00:00

abstract：:Activation of endothelial nitric-oxide synthase (eNOS) has been shown to occur through various pathways involving increases in the cytosolic Ca(2+) concentration, activation of the phosphatidylinositol-3' kinase/Akt pathway, as well as regulation by other kinases and by protein-protein interactions. We have recently r...

journal_title：Molecular pharmacology

authors： Barsacchi R,Perrotta C,Bulotta S,Moncada S,Borgese N,Clementi E

更新日期：2003-04-01 00:00:00

abstract：:Ribavirin used in therapies against hepatitis C virus (HCV) is potentially efficient against other viruses but presents a high cytotoxicity. Several ribavirin triphosphate analogs modified on the ribose moiety were synthesized and tested in vitro on the RNA polymerases of HCV, phage T7, and HIV-1 reverse transcriptase...

journal_title：Molecular pharmacology

authors： Gallois-Montbrun S,Chen Y,Dutartre H,Sophys M,Morera S,Guerreiro C,Schneider B,Mulard L,Janin J,Veron M,Deville-Bonne D,Canard B

更新日期：2003-03-01 00:00:00

abstract：:Molecular cloning of membrane-spanning mammalian adenylyl cyclases (ACs) has led to the discovery of nine different isotypes, making ACs potentially useful therapeutic targets. This study investigated the mechanism by which fungicidal nitroimidazole compounds modulate AC activity. Current evidence indicates that biolo...

journal_title：Molecular pharmacology

authors： Haunsø A,Simpson J,Antoni FA

更新日期：2003-03-01 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：:Several structural subclasses of ligands bind to the benzodiazepine (BZD) binding site of the GABA(A) receptor. Previous studies from this laboratory have suggested that imidazobenzodiazepines (i-BZDs, e.g., Ro 15-1788) require domains in the BZD binding site for high-affinity binding that are distinct from the requir...

journal_title：Molecular pharmacology

authors： Kucken AM,Teissére JA,Seffinga-Clark J,Wagner DA,Czajkowski C

更新日期：2003-02-01 00:00:00

abstract：:The induction of human inducible nitric-oxide synthase (iNOS) expression depends (among other factors) on activation of the signal transducer and activator of transcription 1 (STAT1) pathway. Therefore, the STAT1 pathway may be an appropriate target for the development of inhibitors of iNOS expression. HeLa S3 cells t...

journal_title：Molecular pharmacology

authors： Yao Y,Hausding M,Erkel G,Anke T,Förstermann U,Kleinert H

更新日期：2003-02-01 00:00:00

abstract：:In the hippocampus, two distinct forms of GABAergic inhibition have been identified, phasic inhibitory postsynaptic currents that are the consequence of the vesicular release of GABA and a tonic conductance that is activated by low ambient concentrations of extracellular GABA. It is not known what accounts for the dis...

journal_title：Molecular pharmacology

authors： Yeung JY,Canning KJ,Zhu G,Pennefather P,MacDonald JF,Orser BA

更新日期：2003-01-01 00:00:00

abstract：:GH3 cells show spontaneous activity characterized by bursts of action potentials and oscillations in [Ca 2+]i. This activity is modulated by the activation of exogenously expressed opioid receptors. In GH3 cells expressing only micro receptors (GH3MOR cells), the micro receptor-specific ligand [D-Ala2,N-Me-Phe4,Gly5-o...

journal_title：Molecular pharmacology

authors： Charles AC,Mostovskaya N,Asas K,Evans CJ,Dankovich ML,Hales TG

更新日期：2003-01-01 00:00:00

abstract：:Comparative molecular field analysis (CoMFA) predicts that the large electrostatic field around the phosphate groups of ATP plays a crucial role in stabilizing the open state of the cardiac ryanodine receptor (RyR) channel. We therefore investigated the effects of adenosine-5'-(beta,gamma-methylenetriphosphate) (AMP-P...

journal_title：Molecular pharmacology

authors： Chan WM,Welch W,Sitsapesan R

更新日期：2003-01-01 00:00:00

abstract：:Differential display reverse transcription-polymerase chain reaction was used to identify mRNAs that are differentially expressed in the brain of rats treated chronically with the reference tricyclic antidepressant, imipramine, in comparison with control rats. The gene encoding for a mutation suppressor for Sec4-8 yea...

journal_title：Molecular pharmacology

authors： Andriamampandry C,Muller C,Schmidt-Mutter C,Gobaille S,Spedding M,Aunis D,Maitre M

更新日期：2002-12-01 00:00:00

abstract：:Lead (Pb(2+)) is a well-known inhibitor of voltage-dependent Ca(2+) channels in their native environments in several types of cells. However, its effects on discrete Ca(2+) channel phenotypes in isolation have not been well studied. We compared how specific subtypes of human neuronal high-voltage-activated Ca(2+) chan...

journal_title：Molecular pharmacology

authors： Peng S,Hajela RK,Atchison WD

更新日期：2002-12-01 00:00:00

abstract：:We demonstrated previously that nonsteroidal anti-inflammatory drugs (NSAIDs) increased p27(Kip1) by inhibiting protein degradation to suppress the proliferation of human lung cancer cells. In this study, we elucidate the molecular mechanism by which NSAIDs modulate p27(Kip1) proteolysis. Immunoblotting and in vitro u...

journal_title：Molecular pharmacology

authors： Huang YC,Chuang LY,Hung WC

更新日期：2002-12-01 00:00:00

abstract：:A number of different agonists activate G protein-coupled receptors to stimulate adenylyl cyclase (AC), increase cAMP formation, and promote relaxation in vascular smooth muscle. To more fully understand this stimulation of AC, we assessed the expression, regulation, and compartmentation of AC isoforms in rat aortic s...

journal_title：Molecular pharmacology

authors： Ostrom RS,Liu X,Head BP,Gregorian C,Seasholtz TM,Insel PA

更新日期：2002-11-01 00:00:00

abstract：:The heart is richly endowed with K(ATP) channels, which function as biological sensors, regulating membrane potentials and electrical excitability in response to metabolic alterations. We recently reported that the cytochrome P450 metabolites of arachidonic acid, epoxyeicosatrienoic acids (EETs), potently activate car...

journal_title：Molecular pharmacology

authors： Lu T,VanRollins M,Lee HC

更新日期：2002-11-01 00:00:00

abstract：:Inhibition of multidrug resistance protein 1 (MRP1) mediated cytostatic drug efflux might be useful in the treatment of drug resistant tumors. Because the glutathione (GSH) conjugate of ethacrynic acid (EA), GS-EA, is a good substrate of MRP1, GS-EA derivatives are expected to be good inhibitors of MRP1. To study stru...

journal_title：Molecular pharmacology

authors： Burg D,Wielinga P,Zelcer N,Saeki T,Mulder GJ,Borst P

更新日期：2002-11-01 00:00:00

abstract：:Effects of pimaric acid (PiMA) and eight closely related compounds on large-conductance K(+) (BK) channels were examined using human embryonic kidney (HEK) 293 cells, in which either the alpha subunit of BK channel (HEKBKalpha) or both alpha and beta1 (HEKBKalphabeta1) subunits were heterologously expressed. Effects o...

journal_title：Molecular pharmacology

authors： Imaizumi Y,Sakamoto K,Yamada A,Hotta A,Ohya S,Muraki K,Uchiyama M,Ohwada T

更新日期：2002-10-01 00:00:00