1-[6-[[(17beta)-3-methoxyestra-1,3,5(10)-trien-17-yl]amino]hexyl]-1H-pyrrole-2,5-dione (U73122) selectively inhibits Kir3 and BK channels in a phospholipase C-independent fashion.

abstract：:Large-conductance Ca(2+)-activated K(+) (BK(Ca)) channels play an important role in the regulation of cell physiology in a wide variety of excitable and nonexcitable tissues. Filamin A is a conserved and ubiquitous actin-binding protein that forms perpendicular actin cross-links and contributes to changes in cell shap...

journal_title：Molecular pharmacology

authors： Kim EY,Ridgway LD,Dryer SE

更新日期：2007-09-01 00:00:00

abstract：:The action of tetrahydroaminoacridine (THA), a centrally active cholinesterase inhibitor that may provide symptomatic benefit in Alzheimer's disease, was studied on responses to the excitatory amino acid N-methyl-D-aspartate (NMDA) in cultured hippocampal neurons, using whole-cell voltage-clamp and single-channel reco...

journal_title：Molecular pharmacology

authors： Hershkowitz N,Rogawski MA

更新日期：1991-05-01 00:00:00

abstract：:The gamma-aminobutyric acid-A (GABA(A)) receptor complex is allosterically modulated by a variety of substances, some of clinical importance. Barbiturates and neurosteroids augment GABA-currents and also directly gate the channel. A variety of gamma-butyrolactone analogues also modulate GABA-induced currents, with som...

journal_title：Molecular pharmacology

authors： Williams KL,Tucker JB,White G,Weiss DS,Ferrendelli JA,Covey DF,Krause JE,Rothman SM

更新日期：1997-07-01 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：: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：:Unlike the majority of G protein-coupled receptors, the prostaglandin E(2) (PGE(2)) E-prostanoid 3 (EP3) receptor binds agonist with high affinity that is insensitive to the presence of guanosine 5[prime]-O-(3-thio)triphosphate (GTPγS). We report the identification of mutations that confer GTPγS sensitivity to agonist...

journal_title：Molecular pharmacology

authors： Natarajan C,Hata AN,Hamm HE,Zent R,Breyer RM

更新日期：2013-01-01 00:00:00

abstract：:Isoform-specific expression of endothelin-converting enzyme (ECE)-1, the major big endothelin-processing enzyme, is controlled by alternative promoters. Signaling pathways and transcriptional mechanisms of ECE-1 mRNA expression are largely unknown. To investigate ECE-1 isoform expression after protein kinase C (PKC) a...

journal_title：Molecular pharmacology

authors： Orzechowski HD,Günther A,Menzel S,Zimmermann A,Funke-Kaiser H,Real R,Subkowski T,Zollmann FS,Paul M

更新日期：2001-12-01 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 interactions between beta-adrenergic receptor (beta AR) antagonists and the beta(2)AR were studied with the use of photoaffinity labels. A proteolytic map of the receptor was made and confirmed through amino-terminal amino acid sequencing by locating sites of derivatization. [125I]Iodoazidothiophenylalprenolol (IA...

journal_title：Molecular pharmacology

authors： Hockerman GH,Girvin ME,Malbon CC,Ruoho AE

更新日期：1996-06-01 00:00:00

abstract：:The peripheral cannabinoid receptor (CB2) is a G protein-coupled receptor that is both positively and negatively coupled to the mitogen-activated protein kinase (MAPK) and cAMP pathways, respectively, through a Bordetella pertussis toxin-sensitive G protein. CB2 receptor-transfected Chinese hamster ovary cells exhibit...

journal_title：Molecular pharmacology

authors： Bouaboula M,Desnoyer N,Carayon P,Combes T,Casellas P

更新日期：1999-03-01 00:00:00

abstract：:The retinoid (visual) cycle consists of a series of biochemical reactions needed to regenerate the visual chromophore 11-cis-retinal and sustain vision. Genetic or environmental factors affecting chromophore production can lead to blindness. Using animal models that mimic human retinal diseases, we previously demonstr...

journal_title：Molecular pharmacology

authors： Gao S,Kahremany S,Zhang J,Jastrzebska B,Querubin J,Petersen-Jones SM,Palczewski K

更新日期：2018-05-01 00:00:00

abstract：:The heptadecapeptide orphanin FQ (OFQ) has been identified as the endogenous ligand for a G protein-coupled receptor (OFQ-R), which, despite its high degree of sequence similarity to opioid receptors, fails to bind opioid ligands. We developed two radioligands for the OFQ-R: a tritiated native OFQ peptide ([3H]OFQ) an...

journal_title：Molecular pharmacology

authors： Ardati A,Henningsen RA,Higelin J,Reinscheid RK,Civelli O,Monsma FJ Jr

更新日期：1997-05-01 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：:The two G protein-coupled receptors (GPCRs) C-X-C chemokine receptor type 4 (CXCR4) and atypical chemokine receptor 3 (ACKR3) are part of the class A chemokine GPCR family and represent important drug targets for human immunodeficiency virus (HIV) infection, cancer, and inflammation diseases. CXCR4 is one of only thre...

journal_title：Molecular pharmacology

authors： Adlere I,Caspar B,Arimont M,Dekkers S,Visser K,Stuijt J,de Graaf C,Stocks M,Kellam B,Briddon S,Wijtmans M,de Esch I,Hill S,Leurs R

更新日期：2019-12-01 00:00:00

abstract：:Cadmium is a dangerous metal distributed widely in the environment. Members of our laboratory recently identified the ZIP8 transporter protein, encoded by the mouse Slc39a8 gene, to be responsible for genetic differences in response to cadmium damage of the testis. Stable retroviral infection of the ZIP8 cDNA in mouse...

journal_title：Molecular pharmacology

authors： He L,Girijashanker K,Dalton TP,Reed J,Li H,Soleimani M,Nebert DW

更新日期：2006-07-01 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：:Serotonin [5-hydroxytryptamine (5-HT)] receptors are distinguished pharmacologically by their characteristic affinities for agonists and antagonists. Two serotonin receptors, the 5-HT2 and 5-HT1c, share a number of pharmacologic and structural properties while differing in their affinities for certain agonists and ant...

journal_title：Molecular pharmacology

authors： Choudhary MS,Craigo S,Roth BL

更新日期：1992-10-01 00:00:00

abstract：:A variety of direct and indirect techniques have revealed the existence of ATP-sensitive potassium (KATP) channels in the inner membranes of mitochondria. The molecular identity of these mitochondrial KATP (mitoKATP) channels remains unclear. We used a pharmacological approach to distinguish mitoKATP channels from cla...

journal_title：Molecular pharmacology

authors： Hu H,Sato T,Seharaseyon J,Liu Y,Johns DC,O'Rourke B,Marbán E

更新日期：1999-06-01 00:00:00

abstract：:Glutathione-S-transferase-catalyzed conjugation of glutathione (GSH) to aflatoxin B1-8,9-epoxide plays an important role in preventing binding of this ultimate carcinogen to target macromolecules. Once formed, the aflatoxin B1-epoxide-GSH conjugates are actively extruded from the cell by an unidentified ATP-dependent ...

journal_title：Molecular pharmacology

authors： Loe DW,Stewart RK,Massey TE,Deeley RG,Cole SP

更新日期：1997-06-01 00:00:00

abstract：:Intracellular recordings of membrane potassium current were made from rat locus coeruleus in vitro. The effects of agonists at mu-opioid receptors were studied on neurons from rats that had been chronically treated with morphine; these were compared with actions on neurons from control rats. Tolerance to the opioid-in...

journal_title：Molecular pharmacology

authors： Christie MJ,Williams JT,North RA

更新日期：1987-11-01 00:00:00

abstract：:The effects of saturating concentrations of DDT [1,1,1-trichloro-2,2-bis(p-chlorophenyl)ethane] and the pyrethroid insecticides cismethrin and deltamethrin on alkaloid-dependent activation of the voltage-sensitive sodium channel were studied using measurements of 22Na+ uptake into mouse brain synaptosomes. In survey e...

journal_title：Molecular pharmacology

authors： Bloomquist JR,Soderlund DM

更新日期：1988-05-01 00:00:00

abstract：:Receptors from distant species may have conserved functions despite significant differences in protein sequences. Whereas the noncritical residues are often changed in distant species, the amino acids critical in receptor functions are often conserved. Studying the conserved residues between receptors from distant spe...

journal_title：Molecular pharmacology

authors： Kuei C,Yu J,Zhu J,Wu J,Zhang L,Shih A,Mirzadegan T,Lovenberg T,Liu C

更新日期：2011-11-01 00:00:00

abstract：:Inhibitors of the serotonin transporter (SERT) are widely used antidepressant agents, but the structural mechanism for inhibitory activity and selectivity over the closely related norepinephrine transporter (NET) is not well understood. Here we use a combination of chemical, biological, and computational methods to de...

journal_title：Molecular pharmacology

authors： Andersen J,Stuhr-Hansen N,Zachariassen LG,Koldsø H,Schiøtt B,Strømgaard K,Kristensen AS

更新日期：2014-05-01 00:00:00

abstract：:We investigated the interactions of the anticancer drug vinorelbine with drug efflux transporters and cytochrome P450 3A drug-metabolizing enzymes. Vinorelbine was transported by human multidrug-resistance associated protein (MRP) 2, and Mrp2 knockout mice displayed increased vinorelbine plasma exposure after oral adm...

journal_title：Molecular pharmacology

authors： Lagas JS,Damen CW,van Waterschoot RA,Iusuf D,Beijnen JH,Schinkel AH

更新日期：2012-10-01 00:00:00

abstract：:An azido derivative of [3H2](2S, 3S)-cis-2-(diphenylmethyl)-N-((2-methoxyphenyl) methyl)-1-azabicyclo[2.2.2]octon-3-amine (CP-96,345), a potent nonpeptide antagonist of the substance P (SP) (neurokinin-1) receptor, was synthesized and shown to have an affinity for the human SP receptor similar to that of the parent co...

journal_title：Molecular pharmacology

authors： MacDonald D,Silberman SC,Lowe JA 3rd,Drozda SE,Leeman SE,Boyd ND

更新日期：1996-05-01 00:00:00

abstract：:Prokaryotes produce a variety of toxins that affect genomic function of both eukaryotes and prokaryotes. The 375-base pair bacterial gene Streptoalloteichus hindustanus (Sh) ble encodes a small protein, Streptoalloteichus hindustanus bleomycin resistance protein (BRP), that inhibits in vitro DNA cleavage by the prokar...

journal_title：Molecular pharmacology

authors： Calmels TP,Mistry JS,Watkins SC,Robbins PD,McGuire R,Lazo JS

更新日期：1993-12-01 00:00:00

abstract：:The mammalian copper transporter 1 (CTR1) is responsible for the uptake of copper from the extracellular space. In this study, we used an isogenic pair of CTR1(+/+) and CTR1(-/-) mouse embryo fibroblasts to examine the contribution of CTR1 to the influx of cisplatin (DDP), carboplatin (CBDCA), oxaliplatin (L-OHP), and...

journal_title：Molecular pharmacology

authors： Larson CA,Blair BG,Safaei R,Howell SB

更新日期：2009-02-01 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：: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：:Variant neuroblastoma cell clones were selected for resistance to the cytotoxic effects of neurotoxins that cause persistent activation of sodium channels. Three classes of variant clones were obtained: sodium channel-deficient clones, which have markedly reduced numbers of functional sodium channels; scorpion toxin-r...

journal_title：Molecular pharmacology

authors： Costa MR,Catterall WA

更新日期：1982-07-01 00:00:00