abstract：:The irreversible proteolytic nature of protease-activated receptor-2 (PAR2) activation suggests that mechanism(s) responsible for termination of receptor signaling are critical determinants of the magnitude and duration of PAR2-elicited cellular responses. Rapid desensitization of activated G-protein-coupled receptors...

journal_title：Molecular pharmacology

authors： Stalheim L,Ding Y,Gullapalli A,Paing MM,Wolfe BL,Morris DR,Trejo J

更新日期：2005-01-01 00:00:00

abstract：:Amphetamine congeners [e.g., 3,4-methylenedioxymetamphetamine (MDMA), or "ecstasy"] are substrates for monoamine transporters (i.e., the transporters for serotonin, norepinephrine, and dopamine); however, their in vivo-action relies on their ability to promote monoamine efflux. The mechanistic basis for this counter t...

journal_title：Molecular pharmacology

authors： Seidel S,Singer EA,Just H,Farhan H,Scholze P,Kudlacek O,Holy M,Koppatz K,Krivanek P,Freissmuth M,Sitte HH

更新日期：2005-01-01 00:00:00

abstract：:The liver is the only solid organ that can respond to major tissue loss or damage by regeneration to restore liver biomass. The aryl hydrocarbon receptor (AhR) agonist 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) can disrupt the regenerative process, as evidenced by suppression of DNA synthesis in rat primary hepatocyte...

journal_title：Molecular pharmacology

authors： Huang G,Elferink CJ

更新日期：2005-01-01 00:00:00

abstract：:Cannabinoids have been implicated in the reduction of glioma growth. The present study investigated a possible relationship between the recently shown induction of cyclooxygenase (COX)-2 expression by the endocannabinoid analog R(+)methanandamide [R(+)-MA] and its effect on the viability of H4 human neuroglioma cells....

journal_title：Molecular pharmacology

authors： Hinz B,Ramer R,Eichele K,Weinzierl U,Brune K

更新日期：2004-12-01 00:00:00

abstract：:Inhibitors of the proteasome, a multicatalytic proteinase complex responsible for intracellular proteolysis, activate programmed cell death in part through the c-Jun-N-terminal kinase (JNK). Proteasome inhibitors also induce mitogen-activated protein kinase phosphatase-1 (MKP-1), however, which can inactivate JNK, and...

journal_title：Molecular pharmacology

authors： Small GW,Shi YY,Edmund NA,Somasundaram S,Moore DT,Orlowski RZ

更新日期：2004-12-01 00:00:00

abstract：:GABAA receptors are predominantly composed of alphabetagamma and alphabetadelta isoforms in the brain. It has been proposed that alphabetagamma receptors mediate phasic inhibition, whereas alphabetadelta receptors mediate tonic inhibition. Propofol (2,6-di-isopropylphenol), a widely used anesthetic drug, exerts its ef...

journal_title：Molecular pharmacology

authors： Feng HJ,Macdonald RL

更新日期：2004-12-01 00:00:00

abstract：:Folate receptor-targeted cancer therapies constitute a promising treatment for the approximately one third of human cancers that overexpress the folate receptor (FR). However, the potencies of all folate-receptor targeted therapies depend on 1) the rate of folate-linked drug conjugate binding to the cancer cell surfac...

journal_title：Molecular pharmacology

authors： Paulos CM,Reddy JA,Leamon CP,Turk MJ,Low PS

更新日期：2004-12-01 00:00:00

abstract：:The human mu-opioid receptor (HmuOR) is a G-protein coupled receptor that mediates analgesia, euphoria and other important central and peripheral neurological functions. In this study, we found in a yeast two-hybrid screen that a protein kinase C-interacting protein (PKCI) specifically interacts with the C terminus of...

journal_title：Molecular pharmacology

authors： Guang W,Wang H,Su T,Weinstein IB,Wang JB

更新日期：2004-11-01 00:00:00

abstract：:Combinations of coimmunoprecipitation, single-cell fluorescence resonance energy transfer, and cell-surface time-resolved fluorescence resonance energy transfer demonstrated protein-protein interactions and quaternary structure for the alpha(1b)-adrenoceptor. Self-association of transmembrane domain 1 and its interact...

journal_title：Molecular pharmacology

authors： Carrillo JJ,López-Giménez JF,Milligan G

更新日期：2004-11-01 00:00:00

abstract：:Maurotoxin (MTX) is a potent blocker of human voltage-activated Kv1.2 and intermediate-conductance calcium-activated potassium channels, hIKCa1. Because its blocking affinity on both channels is similar, although the pore region of these channels show only few conserved amino acids, we aimed to characterize the bindin...

journal_title：Molecular pharmacology

authors： Visan V,Fajloun Z,Sabatier JM,Grissmer S

更新日期：2004-11-01 00:00:00

abstract：:The observations from Dunlap and Fischbach that transmitter-mediated shortening of the duration of action potentials could be caused by a decrease in calcium conductance led to numerous studies of the mechanisms of modulation of voltage-dependent calcium channels. Calcium channels are well known targets for inhibition...

journal_title：Molecular pharmacology

authors： Strock J,Diversé-Pierluissi MA

更新日期：2004-11-01 00:00:00

abstract：:The molecular determinants of high-affinity human ether-a-go-go-related gene (HERG) potassium channel blockade by methanesulfonanilides include two aromatic residues (Phe656 and Tyr652) on the inner helices (S6) and residues on the pore helices that face into the inner cavity, but determinants for lower-affinity HERG ...

journal_title：Molecular pharmacology

authors： Witchel HJ,Dempsey CE,Sessions RB,Perry M,Milnes JT,Hancox JC,Mitcheson JS

更新日期：2004-11-01 00:00:00

abstract：:The catestatin fragment of chromogranin A is an endogenous inhibitor of nicotinic cholinergic transmission, functioning in negative feedback control of catecholamine secretion. We explored naturally occurring polymorphisms in the amino acid sequence of catestatin. Three human variants were identified: Gly364Ser, Pro37...

journal_title：Molecular pharmacology

authors： Mahata SK,Mahata M,Wen G,Wong WB,Mahapatra NR,Hamilton BA,O'Connor DT

更新日期：2004-11-01 00:00:00

abstract：:GABAA receptors are modulated by a variety of compounds, including the neurosteroids and barbiturates. Although the effects of barbiturates on alphabetagamma isoforms, thought to dominate phasic (synaptic) GABAergic inhibition, have been extensively studied, the effects of pentobarbital on kinetic properties of alphab...

journal_title：Molecular pharmacology

authors： Feng HJ,Bianchi MT,Macdonald RL

更新日期：2004-10-01 00:00:00

abstract：:Agonist stimulation of group III metabotropic glutamate receptors (mGluRs) induces an inhibition of neurotransmitter release from neurons. The group III mGluRs are pharmacologically defined by activation with the glutamate analog L-amino-4-phosphonobutyric acid (L-AP4). The affinities of these receptors for L-AP4 and ...

journal_title：Molecular pharmacology

authors： Rosemond E,Wang M,Yao Y,Storjohann L,Stormann T,Johnson EC,Hampson DR

更新日期：2004-10-01 00:00:00

abstract：:Proliferation of activated T cells and CD56 bright natural killer (Cytokine Growth Factor Rev 13:169-183, 1995) cells caused by interleukin-2 (IL-2) has been exploited in IL-2-based therapies for the treatment of metastatic renal cell carcinoma and melanoma (J Clin Oncol 13:688-696, 1995; J Clin Oncol 17: 2105-2116, 1...

journal_title：Molecular pharmacology

authors： Rao BM,Driver I,Lauffenburger DA,Wittrup KD

更新日期：2004-10-01 00:00:00

abstract：:At the vertebrate neuromuscular junction (nmj), ATP is known to be coreleased with acetylcholine from the synaptic vesicles. We have previously shown that the P2Y1 receptor is localized at the nmj. Here, we extend the findings to show that another nucleotide receptor, P2Y2, is also localized there and with P2Y1 jointl...

journal_title：Molecular pharmacology

authors： Tung EK,Choi RC,Siow NL,Jiang JX,Ling KK,Simon J,Barnard EA,Tsim KW

更新日期：2004-10-01 00:00:00

abstract：:Ubiquitination plays a crucial role in regulating protein turnover. Here we show that ubiquitination regulates the stability of the MDR1 gene product, P-glycoprotein, thereby affecting the functions of this membrane transporter that mediates multidrug resistance. We found that P-glycoprotein was constitutively ubiquit...

journal_title：Molecular pharmacology

authors： Zhang Z,Wu JY,Hait WN,Yang JM

更新日期：2004-09-01 00:00:00

abstract：:We have previously reported that, depending on the dose, nitric oxide (NO)-generating agents exert a dual facilitatory and inhibitory action on glutamatergic transmission on the rostral ventrolateral medulla (RVLM) neurons. The molecular mechanisms underlying the NO-mediated synaptic inhibition have not yet been defin...

journal_title：Molecular pharmacology

authors： Huang CC,Chan SH,Hsu KS

更新日期：2004-09-01 00:00:00

abstract：:Vinflunine, the newest fluorinated Vinca alkaloid, currently in phase III clinical trials, targets the microtubule network to induce mitotic block and apoptosis by mechanisms that remain unclear. In the current study, we investigated the apoptotic pathways induced by a wide range of vinflunine concentrations in SK-N-S...

journal_title：Molecular pharmacology

authors： Pourroy B,Carré M,Honoré S,Bourgarel-Rey V,Kruczynski A,Briand C,Braguer D

更新日期：2004-09-01 00:00:00

abstract：:Bupropion is an atypical antidepressant that also has usefulness as a smoking-cessation aid. Because hydroxybupropion, a major metabolite of bupropion, is believed to contribute to its antidepressant activity, this metabolite may also contribute to the smoking-cessation properties of bupropion. This study investigated...

journal_title：Molecular pharmacology

authors： Damaj MI,Carroll FI,Eaton JB,Navarro HA,Blough BE,Mirza S,Lukas RJ,Martin BR

更新日期：2004-09-01 00:00:00

abstract：:Pharmacological studies suggest a role for CB1 cannabinoid receptors (CB1R) in regulating neurogenesis in the adult brain. To investigate this possibility, we measured neurogenesis by intraperitoneal injection of bromodeoxyuridine (BrdU), which labels newborn neurons, in wild-type and CB1R-knockout (CB1R-KO) mice. CB1...

journal_title：Molecular pharmacology

authors： Jin K,Xie L,Kim SH,Parmentier-Batteur S,Sun Y,Mao XO,Childs J,Greenberg DA

更新日期：2004-08-01 00:00:00

abstract：:Prostaglandin E(2) (PGE(2)), originally discovered as a pro-inflammatory mediator, also inhibits several chemoattractant-elicited neutrophil functions, including adhesion, secretion of cytotoxic enzymes, production of superoxide anions, and chemotaxis. In this study, we have examined the effects of PGE(2) and prostagl...

journal_title：Molecular pharmacology

authors： Burelout C,Thibault N,Levasseur S,Simard S,Naccache PH,Bourgoin SG

更新日期：2004-08-01 00:00:00

abstract：:There are now several examples of single G protein-coupled receptors to which binding of specific agonists causes differential effects on the associated signaling pathways. The dopamine D(2) receptor is of special importance because the selective activation of functional pathways has been shown both in vitro and in si...

journal_title：Molecular pharmacology

authors： Gay EA,Urban JD,Nichols DE,Oxford GS,Mailman RB

更新日期：2004-07-01 00:00:00

abstract：:Ovarian cancer is the leading cause of death from gynecological malignancy and has the worst prognosis of all gynecological cancers. Vascular endothelial growth factor (VEGF) plays an important role in ovarian cancer development. 9-beta-D-Arabinofuranosyl-2-fluoroadenine (Fara-A), a nucleotide analog, is frequently us...

journal_title：Molecular pharmacology

authors： Fang J,Cao Z,Chen YC,Reed E,Jiang BH

更新日期：2004-07-01 00:00:00

abstract：:The lymphocyte potassium channel Kv1.3 is widely regarded as a promising new target for immunosuppression. To identify a potent small-molecule Kv1.3 blocker, we synthesized a series of 5-phenylalkoxypsoralens and tested them by whole-cell patch clamp. The most potent compound of this series, 5-(4-phenylbutoxy)psoralen...

journal_title：Molecular pharmacology

authors： Vennekamp J,Wulff H,Beeton C,Calabresi PA,Grissmer S,Hänsel W,Chandy KG

更新日期：2004-06-01 00:00:00

abstract：:The level of cellular ceramide, an apoptotic rheostat, is increased by sphingomyelinase or de novo synthesis. The expression of the glutathione S-transferase (GST) gene, whose induction accounts for cell viability, is regulated by activation of CCAAT/enhancer binding protein-beta (C/EBPbeta) and NF-E2-related factor-2...

journal_title：Molecular pharmacology

authors： Park IN,Cho IJ,Kim SG

更新日期：2004-06-01 00:00:00

abstract：:Undesired block of human ERG1 potassium channels is the basis for cardiac side effects of many different types of drugs. Therefore, it is important to know exactly why some drugs particularly bind to these channels with high affinity. Upon expression in mammalian cells and Xenopus laevis oocytes, we investigated the i...

journal_title：Molecular pharmacology

authors： Gessner G,Zacharias M,Bechstedt S,Schönherr R,Heinemann SH

更新日期：2004-05-01 00:00:00

abstract：:Resistance to cisplatin, one of the most widely used anticancer chemotherapeutic agents, is a major clinical problem. There is no effective way to predict development of cisplatin resistance in cancers. As determined by reverse transcription-polymerase chain reaction and Western blotting, the expression of gamma-caten...

journal_title：Molecular pharmacology

authors： Liang XJ,Shen DW,Gottesman MM

更新日期：2004-05-01 00:00:00

abstract：:Isoproterenol increases and decreases contractile force at low and high concentrations, respectively, through beta(2)-adrenoceptors overexpressed in transgenic mouse heart (TG4), consistent with activation of both G(s) and G(i) proteins. Using TG4 hearts, we demonstrated that epinephrine behaves like isoproterenol, bu...

journal_title：Molecular pharmacology

authors： Heubach JF,Ravens U,Kaumann AJ

更新日期：2004-05-01 00:00:00

abstract：:We investigated the mechanisms of MDR1 gene activation by CCAAT/enhancer binding protein beta (C/EBPbeta, or nuclear factor for interleukin 6) in human cancer cells. Transfection of the breast cancer cell line MCF-7 and its doxorubicin-selected variant MCF-7/ADR by either C/EBPbeta or C/EBPbeta-LIP (a dominant-negativ...

journal_title：Molecular pharmacology

authors： Chen KG,Sale S,Tan T,Ermoian RP,Sikic BI

更新日期：2004-04-01 00:00:00

abstract：:Microglia, as phagocytes and antigen-presenting cells in the central nervous system, are activated in such disease processes as stroke and multiple sclerosis. Because peripheral macrophages are capable of producing endocannabinoids, we have examined endocannabinoid production in a macrophage-colony stimulating factor ...

journal_title：Molecular pharmacology

authors： Carrier EJ,Kearn CS,Barkmeier AJ,Breese NM,Yang W,Nithipatikom K,Pfister SL,Campbell WB,Hillard CJ

更新日期：2004-04-01 00:00:00

abstract：:Valproic acid (VPA) is a widely used antiepileptic agent that is undergoing clinical evaluation for anticancer therapy. We assessed the effects of VPA on angiogenesis in vitro and in vivo. In human umbilical vein endothelial cells, therapeutically relevant concentrations of VPA (0.25 to 1 mM) inhibited proliferation, ...

journal_title：Molecular pharmacology

authors： Michaelis M,Michaelis UR,Fleming I,Suhan T,Cinatl J,Blaheta RA,Hoffmann K,Kotchetkov R,Busse R,Nau H,Cinatl J Jr

更新日期：2004-03-01 00:00:00

abstract：:Vasopressin receptor subtype(s) responsible for stimulation of insulin release from pancreatic beta cells were investigated by using subtype-selective antagonists and mice that were genetically lacking either V1a or V1b receptors. Arginine vasopressin (AVP) increased insulin release from isolated mouse islet cells in ...

journal_title：Molecular pharmacology

authors： Oshikawa S,Tanoue A,Koshimizu TA,Kitagawa Y,Tsujimoto G

更新日期：2004-03-01 00:00:00

abstract：:The present study investigates mRNA and protein levels of A3 adenosine receptors in resting (R) and activated (A) human lymphocytes. The receptors were evaluated by the antagonist radioligand [3H]5-N-(4-methoxyphenyl-carbamoyl)amino-8-propyl-2(2furyl)-pyrazolo-[4,3e]-1,2,4-triazolo-[1,5-c]-pyrimidine ([3H]MRE 3008F20)...

journal_title：Molecular pharmacology

authors： Gessi S,Varani K,Merighi S,Cattabriga E,Avitabile A,Gavioli R,Fortini C,Leung E,Mac Lennan S,Borea PA

更新日期：2004-03-01 00:00:00

abstract：:Cytosolic sulfotransferase (SULT)-mediated sulfation plays an essential role in the detoxification of bile acids and is necessary to avoid pathological conditions, such as cholestasis, liver damage, and colon cancer. In this study, using transgenic mice bearing conditional expression of the activated constitutive andr...

journal_title：Molecular pharmacology

authors： Saini SP,Sonoda J,Xu L,Toma D,Uppal H,Mu Y,Ren S,Moore DD,Evans RM,Xie W

更新日期：2004-02-01 00:00:00

abstract：:CaV2.3 subunits are expressed in neuronal and neuroendocrine cells where they are believed to form native R-type Ca2+ channels. Although R-type currents are involved in triggering neurotransmitter and hormone secretion, little is known about their modulation. Previous studies have shown that muscarinic acetylcholine r...

journal_title：Molecular pharmacology

authors： Bannister RA,Melliti K,Adams BA

更新日期：2004-02-01 00:00:00

abstract：:Acetylsalicylic acid (aspirin) is a cyclooxygenase (COX) inhibitor, yet some of its therapeutic effects are thought to derive from mechanisms unrelated to prostaglandin synthesis inhibition. In human intestinal myofibroblasts, aspirin, at therapeutic doses, had the unexpected effect of inducing prolonged COX-2 express...

journal_title：Molecular pharmacology

authors： Mifflin RC,Saada JI,Di Mari JF,Valentich JD,Adegboyega PA,Powell DW

更新日期：2004-02-01 00:00:00

abstract：:This article describes the expected phenotypic behavior of all types of ligands in constitutively active receptor systems and, in particular, the molecular mechanisms of inverse agonism. The possible physiological relevance of inverse agonism also is discussed. Competitive antagonists with the molecular property of ne...

journal_title：Molecular pharmacology

authors： Kenakin T

更新日期：2004-01-01 00:00:00

abstract：:Styrylquinoline derivatives (SQ) efficiently inhibit the 3'-processing activity of integrase (IN) with IC50 values of between 0.5 and 5 microM. We studied the mechanism of action of these compounds in vitro. First, we used steady-state fluorescence anisotropy to assay the effects of the SQ derivatives on the formation...

journal_title：Molecular pharmacology

authors： Deprez E,Barbe S,Kolaski M,Leh H,Zouhiri F,Auclair C,Brochon JC,Le Bret M,Mouscadet JF

更新日期：2004-01-01 00:00:00