abstract：:Cardiac-directed expression of AC6 has pronounced favorable effects on cardiac function possibly not linked with cAMP production. To determine rigorously whether cAMP generation is required for the beneficial effects of increased AC6 expression, we generated a catalytically inactive AC6 mutant (AC6mut) that has marked...

journal_title：Molecular pharmacology

authors： Gao MH,Tang T,Lai NC,Miyanohara A,Guo T,Tang R,Firth AL,Yuan JX,Hammond HK

更新日期：2011-03-01 00:00:00

abstract：:The human dopamine and norepinephrine transporters (hDAT and hNET, respectively) control neurotransmitter levels within the synaptic cleft and are the site of action for amphetamine (AMPH) and cocaine. We investigated the role of a threonine residue within the highly conserved and putative phosphorylation sequence RET...

journal_title：Molecular pharmacology

authors： Guptaroy B,Fraser R,Desai A,Zhang M,Gnegy ME

更新日期：2011-03-01 00:00:00

abstract：:Although G protein-coupled receptors are often categorized in terms of their primary coupling to a given type of Gα protein subunit, it is now well established that many show promiscuous coupling and activate multiple signaling pathways. Furthermore, some agonists selectively activate signaling pathways by promoting i...

journal_title：Molecular pharmacology

authors： Evans BA,Broxton N,Merlin J,Sato M,Hutchinson DS,Christopoulos A,Summers RJ

更新日期：2011-02-01 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：:Melanoma differentiation associated gene-7 (mda-7)/interleukin-24 (IL-24), a member of the IL-10 cytokine gene family, preferentially induces cell death in neoplastic epithelial cells types while sparing their normal counterparts. The effects of mda-7/IL-24 in acute myeloid leukemia (AML) cells have not been extensive...

journal_title：Molecular pharmacology

authors： Rahmani M,Mayo M,Dash R,Sokhi UK,Dmitriev IP,Sarkar D,Dent P,Curiel DT,Fisher PB,Grant S

更新日期：2010-12-01 00:00:00

abstract：:Studies in vertebrate neuromuscular synapses have revealed previously that ATP, via P2Y receptors, plays a critical role in regulating postsynaptic gene expressions. An equivalent regulatory role of ATP and its P2Y receptors would not necessarily be expected for the very different situation of the brain synapses, but ...

journal_title：Molecular pharmacology

authors： Siow NL,Choi RC,Xie HQ,Kong LW,Chu GK,Chan GK,Simon J,Barnard EA,Tsim KW

更新日期：2010-12-01 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：:The seven-transmembrane receptor Smoothened (Smo) is the major component involved in signal transduction of the Hedgehog (Hh) morphogens. Smo inhibitors represent a promising alternative for the treatment of several types of cancers linked to abnormal Hh signaling. Here, on the basis of experimental data, we generated...

journal_title：Molecular pharmacology

authors： Manetti F,Faure H,Roudaut H,Gorojankina T,Traiffort E,Schoenfelder A,Mann A,Solinas A,Taddei M,Ruat M

更新日期：2010-10-01 00:00:00

abstract：:The availability of high-affinity agonists for peroxisome proliferator-activated receptor-beta/delta (PPARbeta/delta) has led to significant advances in our understanding of the functional role of PPARbeta/delta. In this study, a new PPARbeta/delta antagonist, 4-chloro-N-(2-{[5-trifluoromethyl)-2-pyridyl]sulfonyl}ethy...

journal_title：Molecular pharmacology

authors： Palkar PS,Borland MG,Naruhn S,Ferry CH,Lee C,Sk UH,Sharma AK,Amin S,Murray IA,Anderson CR,Perdew GH,Gonzalez FJ,Müller R,Peters JM

更新日期：2010-09-01 00:00:00

abstract：:Histone deacetylase inhibitors (HDACis) are currently in trial or are in clinical use for the treatment of a number of tumor types. The clinical efficacy of HDACis can be partly attributed to the modulation of the cell cycle by the HDACis. Here, we have examined the effects of N-(2-aminophenyl)-4-((4-pyridin-3-ylpyrim...

journal_title：Molecular pharmacology

authors： Chia K,Beamish H,Jafferi K,Gabrielli B

更新日期：2010-09-01 00:00:00

abstract：:Inhibition of cannabinoid receptor 1 (CB1) has shown efficacy in reducing body weight and improving metabolic parameters, with the effects correlating with target engagement in the brain. The peripheral effects of inhibiting the CB1 receptor has been appreciated through studies in diet-induced obese and liver-specific...

journal_title：Molecular pharmacology

authors： Zhao W,Fong O,Muise ES,Thompson JR,Weingarth D,Qian S,Fong TM

更新日期：2010-09-01 00:00:00

abstract：:Stimulation of alpha1-adrenoreceptors (alpha1-AR) acutely alters ion channel behavior via several signaling pathways [calcium and protein kinase C (PKC)]. Little is known about sustained alpha1-adrenergic/PKC signaling and channel regulation as may occur during cardiovascular disease states. Here we describe the effec...

journal_title：Molecular pharmacology

authors： Chen J,Chen K,Sroubek J,Wu ZY,Thomas D,Bian JS,McDonald TV

更新日期：2010-08-01 00:00:00

abstract：:The anticancer agent 2-cyano-3,12-dioxooleana-1,9-dien-28-oic acid (CDDO) and its methyl ester (CDDO-Me) typically induce a broad spectrum of growth-inhibitory, proapoptotic, and antiangiogenic responses. Treatment of Panc1, Panc28, and L3.6pL pancreatic cancer cells with low micromolar concentrations of CDDO or CDDO-...

journal_title：Molecular pharmacology

authors： Jutooru I,Chadalapaka G,Abdelrahim M,Basha MR,Samudio I,Konopleva M,Andreeff M,Safe S

更新日期：2010-08-01 00:00:00

abstract：:The MUC1 C-terminal transmembrane subunit (MUC1-C) oncoprotein is a direct activator of the canonical nuclear factor-kappaB (NF-kappaB) RelA/p65 pathway and is aberrantly expressed in human multiple myeloma cells. However, it is not known whether multiple myeloma cells are sensitive to the disruption of MUC1-C functio...

journal_title：Molecular pharmacology

authors： Yin L,Ahmad R,Kosugi M,Kufe T,Vasir B,Avigan D,Kharbanda S,Kufe D

更新日期：2010-08-01 00:00:00

abstract：:A functional interaction between peroxisome proliferator-activated receptor alpha (PPARalpha) and components of the circadian clock has been suggested, but whether these transcriptional factors interact to regulate the expression of their target genes remains obscure. Here we used a PPARalpha ligand, bezafibrate, to s...

journal_title：Molecular pharmacology

authors： Oishi K,Koyanagi S,Matsunaga N,Kadota K,Ikeda E,Hayashida S,Kuramoto Y,Shimeno H,Soeda S,Ohdo S

更新日期：2010-07-01 00:00:00

abstract：:The GABA type A receptor (GABA(A)R) is the major inhibitory receptor in the mammalian central nervous system and the target of numerous pharmaceuticals. The alpha-subunit of these pentameric Cys-loop neurotransmitter-gated ion channels contributes to the binding of both GABA and allosteric modulators such as the benzo...

journal_title：Molecular pharmacology

authors： Hanek AP,Lester HA,Dougherty DA

更新日期：2010-07-01 00:00:00

abstract：:Polycyclic aromatic hydrocarbons (PAHs) are widely distributed environmental toxicants derived from sources that include cigarette smoke, petroleum distillation, gas- and diesel-engine exhaust, and charcoal-grilled food. The gastrointestinal tract is the principal route of PAH exposures, even when inhaled. The most th...

journal_title：Molecular pharmacology

authors： Shi Z,Dragin N,Gálvez-Peralta M,Jorge-Nebert LF,Miller ML,Wang B,Nebert DW

更新日期：2010-07-01 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：:Multiple lines of evidence indicate that the platinum-containing cancer drugs enter cells, are distributed to various subcellular compartments, and are exported from cells via transporters that evolved to manage copper homeostasis. The cytotoxicity of the platinum drugs is directly related to how much drug enters the ...

journal_title：Molecular pharmacology

authors： Howell SB,Safaei R,Larson CA,Sailor MJ

更新日期：2010-06-01 00:00:00

abstract：:The protease-activated receptors (PAR1 and PAR2) are unusual G protein-coupled receptors that are activated by distinct serine proteases and are coexpressed in many different cell types. Limited recent evidence suggests these closely related receptors regulate different physiological outputs in the same cell, although...

journal_title：Molecular pharmacology

authors： McCoy KL,Traynelis SF,Hepler JR

更新日期：2010-06-01 00:00:00

abstract：:Prolonged ethanol exposure causes central nervous system hyperexcitability that involves a loss of GABAergic inhibition. We previously demonstrated that long-term ethanol exposure enhances the internalization of synaptic GABA(A) receptors composed of alpha1beta2/3gamma2 subunits. However, the mechanisms of ethanol-med...

journal_title：Molecular pharmacology

authors： Kumar S,Suryanarayanan A,Boyd KN,Comerford CE,Lai MA,Ren Q,Morrow AL

更新日期：2010-05-01 00:00:00

abstract：:Stromal cell-derived factor-1 (SDF-1/CXCL-12) and vascular endothelial growth factor (VEGF), which can be secreted by hypoxic tumors, promote the generation of new blood vessels. These potent angiogenic factors stimulate endothelial cell migration via the activation of Rho GTPases and the phosphatidylinositol 3-kinase...

journal_title：Molecular pharmacology

authors： Carretero-Ortega J,Walsh CT,Hernández-García R,Reyes-Cruz G,Brown JH,Vázquez-Prado J

更新日期：2010-03-01 00:00:00

abstract：:Phosphorylation of G protein-coupled receptors (GPCRs) by GPCR kinases (GRKs) is a major mechanism of desensitization of these receptors. GPCR activation of GRKs involves an allosteric site on GRKs distinct from the catalytic site. Although recent studies have suggested an important role of the N- and C-termini and do...

journal_title：Molecular pharmacology

authors： Baameur F,Morgan DH,Yao H,Tran TM,Hammitt RA,Sabui S,McMurray JS,Lichtarge O,Clark RB

更新日期：2010-03-01 00:00:00

abstract：:Increasing data indicate that brain endocannabinoid system plays a role in the effects of antidepressant medications. Here we examined the effect of in vivo exposure to the selective serotonin uptake inhibitor fluoxetine on cannabinoid type 1 (CB(1)) receptor density and functionality in the rat prefrontal cortex (PFC...

journal_title：Molecular pharmacology

authors： Mato S,Vidal R,Castro E,Díaz A,Pazos A,Valdizán EM

更新日期：2010-03-01 00:00:00

abstract：:bTREK-1 K(+) channels set the resting membrane potential of bovine adrenal zona fasciculata (AZF) cells and function pivotally in the physiology of cortisol secretion. Adrenocorticotropic hormone controls the function and expression of bTREK-1 channels through signaling mechanisms that may involve cAMP and downstream ...

journal_title：Molecular pharmacology

authors： Enyeart JA,Liu H,Enyeart JJ

更新日期：2010-03-01 00:00:00

abstract：:The aryl hydrocarbon receptor (AHR) is a ligand-activated transcription factor with constitutive activities and those induced by xenobiotic ligands, such as 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD). One unexplained cellular role for the AHR is its ability to promote cell cycle progression in the absence of exogenous...

journal_title：Molecular pharmacology

authors： Barhoover MA,Hall JM,Greenlee WF,Thomas RS

更新日期：2010-02-01 00:00:00

abstract：:The cytochrome P450 26 family is believed to be responsible for all-trans-retinoic acid (atRA) metabolism and elimination in the human fetus and adults. CYP26A1 and CYP26B1 mRNA is expressed in a tissue-specific manner, and mice in which the CPY26 isoform has been knocked out show distinct malformations and lethality....

journal_title：Molecular pharmacology

authors： Tay S,Dickmann L,Dixit V,Isoherranen N

更新日期：2010-02-01 00:00:00

abstract：:N-formyl peptide receptor (FPR1) and N-formyl peptide receptor-like 1 (FPRL1, now known as FPR2) are G protein-coupled receptors involved in host defense and sensing cellular dysfunction. Because of the potential for FPR1/FPR2 as a therapeutic target, our recent high-throughput screening efforts have focused on the id...

journal_title：Molecular pharmacology

authors： Kirpotina LN,Khlebnikov AI,Schepetkin IA,Ye RD,Rabiet MJ,Jutila MA,Quinn MT

更新日期：2010-02-01 00:00:00

abstract：:The neuropeptides vasoactive intestinal peptide (VIP) and pituitary adenylate cyclase-activating peptide (PACAP) and their class II G protein-coupled receptors VPAC(1), VPAC(2), and PAC(1) play important roles in human physiology. No small molecule modulator has ever been reported for the VIP/PACAP receptors, and ther...

journal_title：Molecular pharmacology

authors： Chu A,Caldwell JS,Chen YA

更新日期：2010-01-01 00:00:00

abstract：:The epithelial sodium channel (ENaC) is believed to represent the rate-limiting step for sodium absorption in the renal collecting duct. Consequently, ENaC is a central effector affecting systemic blood volume and pressure. Sodium and water transport are dysregulated in diabetes mellitus. Peroxisome proliferator-activ...

journal_title：Molecular pharmacology

authors： Pavlov TS,Levchenko V,Karpushev AV,Vandewalle A,Staruschenko A

更新日期：2009-12-01 00:00:00

abstract：:Vitamin A-derived metabolites act as ligands for nuclear receptors controlling the expression of a number of genes. Stereospecific saturation of the C(13)-C(14) double bond of all-trans-retinol by the enzyme, retinol saturase (RetSat), leads to the production of (R)-all-trans-13,14-dihydroretinol. In liver and adipose...

journal_title：Molecular pharmacology

authors： Moise AR,Alvarez S,Domínguez M,Alvarez R,Golczak M,Lobo GP,von Lintig J,de Lera AR,Palczewski K

更新日期：2009-12-01 00:00:00

abstract：:The renal outer medullary potassium channel (ROMK) is expressed in the kidney tubule and critically regulates sodium and potassium balance. The physiological functions of other inward rectifying K(+) (Kir) channels expressed in the nephron, such as Kir7.1, are less well understood in part due to the lack of selective ...

journal_title：Molecular pharmacology

authors： Lewis LM,Bhave G,Chauder BA,Banerjee S,Lornsen KA,Redha R,Fallen K,Lindsley CW,Weaver CD,Denton JS

更新日期：2009-11-01 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 highly specialized metabotropic glutamate receptor type 6 (mGluR6) is postsynaptically localized and expressed only in the dendrites of ON bipolar cells. Upon activation of mGluR6 by glutamate released from photoreceptors, a nonselective cation channel is inhibited, causing these cells to hyperpolarize. Mutations ...

journal_title：Molecular pharmacology

authors： Beqollari D,Betzenhauser MJ,Kammermeier PJ

更新日期：2009-11-01 00:00:00

abstract：:TWIK-related K+ channel TREK1, a background leak K+ channel, has been strongly implicated as the target of several general and local anesthetics. Here, using the whole-cell and single-channel patch-clamp technique, we investigated the effect of lidocaine, a local anesthetic, on the human (h)TREK1 channel heterologousl...

journal_title：Molecular pharmacology

authors： Nayak TK,Harinath S,Nama S,Somasundaram K,Sikdar SK

更新日期：2009-10-01 00:00:00

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：:Many human cancers show constitutive or amplified expression of the transcriptional regulator and oncoprotein Myc, making Myc a potential target for therapeutic intervention. Here we report the down-regulation of Myc activity by reducing the availability of Max, the essential dimerization partner of Myc. Max is expres...

journal_title：Molecular pharmacology

authors： Jiang H,Bower KE,Beuscher AE 4th,Zhou B,Bobkov AA,Olson AJ,Vogt PK

更新日期：2009-09-01 00:00:00

abstract：:Human serum butyrylcholinesterase (Hu BChE) is a promising therapeutic against the toxicity of chemical warfare nerve agents. We have showed previously that recombinant (r) Hu BChE can be expressed at very high levels, 400 to 600 U/ml in mouse blood, by delivering the Hu BChE gene using adenovirus (Ad). Here, we repor...

journal_title：Molecular pharmacology

authors： Chilukuri N,Duysen EG,Parikh K,diTargiani R,Doctor BP,Lockridge O,Saxena A

更新日期：2009-09-01 00:00:00

abstract：:Previous studies suggest that selective antagonists of specific subtypes of muscarinic acetylcholine receptors (mAChRs) may provide a novel approach for the treatment of certain central nervous system (CNS) disorders, including epileptic disorders, Parkinson's disease, and dystonia. Unfortunately, previously reported ...

journal_title：Molecular pharmacology

authors： Sheffler DJ,Williams R,Bridges TM,Xiang Z,Kane AS,Byun NE,Jadhav S,Mock MM,Zheng F,Lewis LM,Jones CK,Niswender CM,Weaver CD,Lindsley CW,Conn PJ

更新日期：2009-08-01 00:00:00

abstract：:The diphosphoinositol polyphosphates ("inositol pyrophosphates") are a specialized subgroup of the inositol phosphate signaling family. This review proposes that many of the current data concerning the metabolic turnover and biological effects of the diphosphoinositol polyphosphates are linked by a common theme: these...

journal_title：Molecular pharmacology

authors： Shears SB

更新日期：2009-08-01 00:00:00