Geranylgeranylacetone protects membranes against nonsteroidal anti-inflammatory drugs.

abstract：:Reversal of the multidrug-resistant (MDR) phenotype is very important for chemotherapy success. In fact, the expression of the MDR1 gene-encoded P-glycoprotein (P-gp) actively expels antitumor agents such as daunomycin (DNM) out of the cells, resulting in drug resistance. We show that upon conjugation to triplex-formi...

journal_title：Molecular pharmacology

authors： Stierlé V,Duca M,Halby L,Senamaud-Beaufort C,Capobianco ML,Laigle A,Jollès B,Arimondo PB

更新日期：2008-05-01 00:00:00

abstract：:The nuclear pregnane X receptor (PXR) and constitutive androstane receptor (CAR) play central roles in protecting the body against environmental chemicals (xenobiotics). PXR and CAR are activated by a wide range of xenobiotics and regulate cytochrome P450 and other genes whose products are involved in the detoxificati...

journal_title：Molecular pharmacology

authors： Maglich JM,Stoltz CM,Goodwin B,Hawkins-Brown D,Moore JT,Kliewer SA

更新日期：2002-09-01 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：:Extracellular ATP activates two distinct types of P2 purinoreceptor-mediated signaling pathways in macrophages, 1) the rapid formation of nonselective pores/channels in the plasma membrane and 2) a guanine nucleotide-binding protein-dependent stimulation of phosphotidylinositol-specific phospholipase C, with subsequen...

journal_title：Molecular pharmacology

authors： Nuttle LC,el-Moatassim C,Dubyak GR

更新日期：1993-07-01 00:00:00

abstract：:mRNA levels for the protooncogene c-fos, measured by Northern blot analysis, were greatly increased in brains of mice undergoing ethanol withdrawal seizures. This increase was transient (levels were increased at the time of the seizure and returned to normal by 24 hr or less after seizure) and was larger in hippocampu...

journal_title：Molecular pharmacology

authors： Dave JR,Tabakoff B,Hoffman PL

更新日期：1990-03-01 00:00:00

abstract：:The vitamin D receptor (VDR) mediates vitamin D signaling in numerous physiological and pharmacological processes, including bone and calcium metabolism, cellular growth and differentiation, immunity, and cardiovascular function. Although transcriptional regulation by VDR has been investigated intensively, an understa...

journal_title：Molecular pharmacology

authors： Choi M,Yamada S,Makishima M

更新日期：2011-12-01 00:00:00

abstract：:Nafazatrom, an antithrombotic and antimetastatic agent containing a pyrazolone functionality, is a reducing substrate for the peroxidase activity of prostaglandin H (PGH) synthase. Nafazatrom inhibits the hydroperoxide-dependent oxidation of phenylbutazone, stimulates the reduction of 15-hydroperoxy-5,8,11,13-eicosate...

journal_title：Molecular pharmacology

authors： Marnett LJ,Siedlik PH,Ochs RC,Pagels WR,Das M,Honn KV,Warnock RH,Tainer BE,Eling TE

更新日期：1984-09-01 00:00:00

abstract：:Understanding the structures of active and inactive agonist- and antagonist-bound receptor complexes is of great interest. In this work, we focus on position 30 of cholecystokinin (CCK) and its spatial approximation with the type A CCK receptor. For this, we developed two photoaffinity labeling probes, replacing the n...

journal_title：Molecular pharmacology

authors： Dong M,Hadac EM,Pinon DI,Miller LJ

更新日期：2005-06-01 00:00:00

abstract：:Recently we identified the serotonin reuptake inhibitor paroxetine as an inhibitor of G protein-coupled receptor kinase 2 (GRK2) that improves cardiac performance in live animals. Paroxetine exhibits up to 50-fold selectivity for GRK2 versus other GRKs. A better understanding of the molecular basis of this selectivity...

journal_title：Molecular pharmacology

authors： Homan KT,Wu E,Wilson MW,Singh P,Larsen SD,Tesmer JJ

更新日期：2014-02-01 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：: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：:Amitriptyline is a classic tricyclic antidepressant (TCA) and has been used to treat the depression and anxiety of patients with cancer, but its relevance to cancer cell apoptosis is not known. In the present study, we demonstrated that amitriptyline inhibited cyclin D2 transactivation and displayed potential antimyel...

journal_title：Molecular pharmacology

authors： Mao X,Hou T,Cao B,Wang W,Li Z,Chen S,Fei M,Hurren R,Gronda M,Wu D,Trudel S,Schimmer AD

更新日期：2011-04-01 00:00:00

abstract：:Identifying novel mechanisms to enhance glucagon-like peptide-1 (GLP-1) receptor signaling may enable nascent medicinal chemistry strategies with the aim of developing new orally available therapeutic agents for the treatment of type 2 diabetes mellitus. Therefore, we tested the hypothesis that selectively modulating ...

journal_title：Molecular pharmacology

authors： Willard FS,Wootten D,Showalter AD,Savage EE,Ficorilli J,Farb TB,Bokvist K,Alsina-Fernandez J,Furness SG,Christopoulos A,Sexton PM,Sloop KW

更新日期：2012-12-01 00:00:00

abstract：:TNP-ATP has become widely recognized as a potent and selective P2X receptor antagonist, and is currently being used to discriminate between subtypes of P2X receptors in a variety of tissues. We have investigated the ability of TNP-ATP to inhibit alpha,beta-methylene ATP (alpha,beta-meATP)-evoked responses in 1321N1 hu...

journal_title：Molecular pharmacology

authors： Burgard EC,Niforatos W,van Biesen T,Lynch KJ,Kage KL,Touma E,Kowaluk EA,Jarvis MF

更新日期：2000-12-01 00:00:00

abstract：:The glucagon-like peptide-1 receptor (GLP-1R) is a key physiological regulator of insulin secretion and a major therapeutic target for the treatment of type II diabetes. However, regulation of GLP-1R function is complex with multiple endogenous peptides that interact with the receptor, including full-length (1-37) and...

journal_title：Molecular pharmacology

authors： Koole C,Wootten D,Simms J,Valant C,Miller LJ,Christopoulos A,Sexton PM

更新日期：2011-09-01 00:00:00

abstract：:alpha2-Adrenergic receptor (alpha(2)-AR) activation in the pregnant rat myometrium at midterm potentiates beta(2)-AR stimulation of adenylyl cyclase (AC) via Gbetagamma regulation of the type II isoform of adenylyl cyclase. However, at term, alpha(2)-AR activation inhibits beta(2)-AR stimulation of AC. This phenomenon...

journal_title：Molecular pharmacology

authors： Limon-Boulez I,Bouet-Alard R,Gettys TW,Lanier SM,Maltier JP,Legrand C

更新日期：2001-02-01 00:00:00

abstract：:Capacitative Ca2+ influx, which occurs in response to mobilization of intracellular Ca2+ stores, is a general feature of many cell types. Although the mechanism of capacitative Ca2+ entry is not known, evidence suggests the involvement of small G proteins that are prenylated on a cysteine residue near their carboxyl t...

journal_title：Molecular pharmacology

authors： Xu Y,Gilbert BA,Rando RR,Chen L,Tashjian AH Jr

更新日期：1996-12-01 00:00:00

abstract：:SC-54628 [1-(2-methylphenyl)-4-butyl-1,3-dihydro-3-[[6-[2-(1H- tetrazol-5-yl)phenyl]-3-pyridinyl]methyl]-2H-imidazol-2-one] and its 1-(2,6-dimethylphenyl)-2H-imidazol-2-one derivative SC-54629 were potent inhibitors of 125I-angiotensin II (125I-AII) binding to rat adrenal cortex angiotensin type 1 (AT1) receptors. SC-...

journal_title：Molecular pharmacology

authors： Olins GM,Chen ST,McMahon EG,Palomo MA,Reitz DB

更新日期：1995-01-01 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：: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：:Based on the available data, we speculated that changes in brain iron metabolism induced by L-DOPA might be associated with the neurotoxicity of L-DOPA. To investigate this possibility, the effects of L-DOPA on the expression of iron influx proteins [transferrin receptor (TfR) and divalent metal transporter 1 (DMT1)],...

journal_title：Molecular pharmacology

authors： Chang YZ,Ke Y,Du JR,Halpern GM,Ho KP,Zhu L,Gu XS,Xu YJ,Wang Q,Li LZ,Wang CY,Qian ZM

更新日期：2006-03-01 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：:We describe the structural and functional features of the human alpha3 nicotinic receptor subunit promoter. A 0.35-kb region immediately upstream of the start codon was identified that when transfected in human neuroblastoma cells was able to drive the expression of the luciferase reporter gene with a strength compara...

journal_title：Molecular pharmacology

authors： Fornasari D,Battaglioli E,Flora A,Terzano S,Clementi F

更新日期：1997-02-01 00:00:00

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 NO/cGMP signaling pathway plays a major role in the cardiovascular system, in which it is involved in the regulation of smooth muscle tone and inhibition of platelet aggregation. Under pathophysiological conditions such as endothelial dysfunction, coronary artery disease, and airway hyperreactivity, smooth muscle ...

journal_title：Molecular pharmacology

authors： Mullershausen F,Lange A,Mergia E,Friebe A,Koesling D

更新日期：2006-06-01 00:00:00

abstract：:Receptors have well-conserved regions that are recognized and activated by hormones and neurotransmitters. Most drugs bind to these sites and mimic or block the action of the native ligands. Using a high-throughput functional screen, we identified a potent and selective M(1) muscarinic receptor agonist from a novel st...

journal_title：Molecular pharmacology

authors： Spalding TA,Trotter C,Skjaerbaek N,Messier TL,Currier EA,Burstein ES,Li D,Hacksell U,Brann MR

更新日期：2002-06-01 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 have identified alpha 2-adrenergic receptors on human erythroleukemia (HEL) cells, a suspension-grown cell line related to human platelets. properties of receptors were assessed in intact cells by binding of the antagonist [3H]yohimbine and by inhibition of cAMP accumulation. [3H]Yohimbine labeled 5900 +/- 2100 rec...

journal_title：Molecular pharmacology

authors： McKernan RM,Howard MJ,Motulsky HJ,Insel PA

更新日期：1987-08-01 00:00:00

abstract：:Expression of the angiotensin II type 1 receptor (AT1-R) mRNA in vascular smooth muscle cells (VSMC) is down-regulated by a variety of agonists, including growth factors, agonists of Galphaq protein-coupled receptors, and activators of adenylyl cyclase. To determine whether cAMP-dependent protein kinases (PKA) partici...

journal_title：Molecular pharmacology

authors： Wang X,Murphy TJ

更新日期：1998-09-01 00:00:00

abstract：:Small-molecule restoration of wild-type structure and function to mutant p53 (so-called mutant reactivation) is a highly sought-after goal in cancer drug development. We previously discovered that small-molecule zinc chelators called zinc metallochaperones (ZMCs) reactivate mutant p53 by restoring zinc binding to zinc...

journal_title：Molecular pharmacology

authors： Yu X,Blanden A,Tsang AT,Zaman S,Liu Y,Gilleran J,Bencivenga AF,Kimball SD,Loh SN,Carpizo DR

更新日期：2017-06-01 00:00:00