Abstract：
:The interaction of quinidine with a cloned human cardiac potassium channel (HK2) expressed in a stable mouse L cell line was studied using the whole-cell tight-seal voltage-clamp technique. Quinidine (20 microM) did not affect the initial sigmoidal activation time course of the current. However, it reduced the peak current and induced a subsequent decline, with a time constant of 8.2 +/- 0.8 msec, to 28 +/- 6% of control (at +60 mV). The concentration dependence of HK2 block at +60 mV yielded an apparent KD of 6 microM and a Hill coefficient of 0.9. The degree of block was voltage dependent. Block increased from 0.60 +/- 0.09 at 0 mV to 0.72 +/- 0.06 at +60 mV with 20 microM quinidine and from 0.39 +/- 0.20 to 0.48 +/- 0.16 with 6 microM. Paired analysis in seven experiments with 20 microM quinidine indicated that the voltage-dependent increase in block was significant (difference, 12 +/- 4%; p less than 0.001). This voltage dependence was described by an equivalent electrical distance delta of 0.19 +/- 0.02, which suggested that at the binding site quinidine experienced 19% of the applied transmembrane electrical field, referenced to the inner surface. Quinidine reduced the tail current amplitude and slowed the time course relative to control, resulting in a "crossover" phenomenon. These data indicate that 1) the charged form of quinidine blocks the HK2 channel after it opens, 2) binding occurs within the transmembrane electrical field (probably in or near the ion permeation pathway), and 3) unbinding is required before the channel can close.
journal_name
Mol Pharmacoljournal_title
Molecular pharmacologyauthors
Snyders J,Knoth KM,Roberds SL,Tamkun MMkeywords:
subject
Has Abstractpub_date
1992-02-01 00:00:00pages
322-30issue
2eissn
0026-895Xissn
1521-0111journal_volume
41pub_type
杂志文章abstract：:The nucleoside analog 5-azacytidine is an archetypical drug for epigenetic cancer therapy, and its clinical effectiveness has been demonstrated in the treatment of myelodysplastic syndromes (MDS) and acute myelogenous leukemia (AML). However, therapy resistance in patients with MDS/AML remains a challenging issue. Mem...
journal_title：Molecular pharmacology
pub_type： 杂志文章
doi：10.1124/mol.113.086801
更新日期：2013-09-01 00:00:00
abstract：:In this work, we evaluate the structural differences of transmembrane helix 3 in rhodopsin and the 5-hydroxytryptamine 1A (5-HT1A) receptor caused by their different amino acid sequence. Molecular dynamics simulations of helix 3 in the 5-HT1A receptor tends to bend toward helix 5, in sharp contrast to helix 3 in rhodo...
journal_title：Molecular pharmacology
pub_type： 杂志文章
doi：10.1124/mol.62.1.15
更新日期：2002-07-01 00:00:00
abstract：:The activities of phosphorylase kinase and myosin light-chain kinase are regulated by Ca2+ binding to calmodulin. However, differences in the activation properties of the purified enzymes are apparent, since calmodulin binds to phosphorylase kinase in the absence of Ca2+ whereas prior formation of a Ca2+ . calmodulin ...
journal_title：Molecular pharmacology
pub_type： 杂志文章
doi：
更新日期：1983-05-01 00:00:00
abstract：:KARs, new semisynthetic antitumor bis-indole derivatives, were found to be inhibitors of tubulin polymerization with lower toxicity than vinblastine or vincristine, used in chemotherapy. Here, we compare the effect of KARs with those of vinblastine and vincristine on cell viability, cell proliferation, and cell cycle ...
journal_title：Molecular pharmacology
pub_type： 杂志文章
doi：10.1124/mol.60.6.1235
更新日期：2001-12-01 00:00:00
abstract：:In the last years, reactive oxygen species (ROS) have been proposed as mediators of proliferative/hypertrophic responses to angiotensin II (Ang II), both in vivo and in vitro. However, the hypothesis that the Ang II-dependent cell contraction could be mediated by ROS, particularly H2O2, has not been tested. Present ex...
journal_title：Molecular pharmacology
pub_type： 杂志文章
doi：10.1124/mol.59.1.104
更新日期：2001-01-01 00:00:00
abstract：:The role of mobilization of intracellular Ca2+ in the adrenergic-stimulated cAMP accumulation in rat pinealocytes was investigated with thapsigargin, an agent that inhibits endoplasmic reticulum Ca2+-ATPase. It was found that although thapsigargin alone had no effect on the basal cAMP accumulation, it potentiated the ...
journal_title：Molecular pharmacology
pub_type： 杂志文章
doi：
更新日期：1996-06-01 00:00:00
abstract：:The bisdioxopiperazines such as (+)-(S)-4,4'-propylenedi-2,6-piperazinedione (dexrazoxane; ICRF-187), 1,2-bis(3,5-dioxopiperazin-1-yl)ethane (ICRF-154), and 4,4'-(1,2-dimethyl-1,2-ethanediyl)bis-2,6-piperazinedione (ICRF-193) are agents that inhibit eukaryotic topoisomerase II, whereas their ring-opened hydrolysis pro...
journal_title：Molecular pharmacology
pub_type： 杂志文章
doi：10.1124/mol.107.036970
更新日期：2007-10-01 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
pub_type： 杂志文章
doi：10.1124/mol.65.6.1475
更新日期：2004-06-01 00:00:00
abstract：:Macrophage production of growth factors for fibroblasts, in particular platelet-derived growth factor B [PDGF(B)] and transforming growth factor-beta (TGF-beta), is thought to be central to the pathogenesis of pulmonary fibrosis. In a search for anti-inflammatory agents that might prevent this process, we asked whethe...
journal_title：Molecular pharmacology
pub_type： 杂志文章
doi：
更新日期：1992-10-01 00:00:00
abstract：:Previous studies have established that two Xbal polymorphic restriction fragments [11.5 and 44 kilobases (kb)] hydridizing to a full length debrisoquin hydroxylase cDNA are associated with two different mutant alleles for the debrisoquin hydroxylase gene (IID6). An independent allele, defined by Xbal 16- and 9-kb frag...
journal_title：Molecular pharmacology
pub_type： 杂志文章
doi：
更新日期：1990-05-01 00:00:00
abstract：:Regulator of G protein signaling (RGS) proteins are a family of approximately 20 proteins that negatively regulate signaling through heterotrimeric G protein-coupled receptors. The RGS proteins act as GTPase-activating proteins (GAPs) for certain Galpha subunits and as effector antagonists for Gqalpha. Mouse RGS14 enc...
journal_title：Molecular pharmacology
pub_type： 杂志文章
doi：10.1124/mol.58.3.569
更新日期：2000-09-01 00:00:00
abstract：:Many progestins have been developed for use in contraception, menopausal hormone therapy, and treatment of gynecological diseases. They are derived from either progesterone or testosterone, and they act by binding to the progesterone receptor (PR), a hormone-inducible transcription factor belonging to the nuclear rece...
journal_title：Molecular pharmacology
pub_type： 杂志文章
doi：10.1124/mol.108.054312
更新日期：2009-06-01 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
pub_type： 杂志文章
doi：10.1124/mol.66.2.293
更新日期：2004-08-01 00:00:00
abstract：:Recently, several classes of compounds have been shown to be potent, selective, and specific inhibitors of human immunodeficiency virus type 1 replication in vitro. These include the tetrahydroimidazo[4,5,1-jk][1,4]-benzodiazepin-2(1H)-one and -thione (TIBO) and the 1-[(2-hydroxyethoxy)methyl]-6-(phenylthio)thymine (H...
journal_title：Molecular pharmacology
pub_type： 杂志文章
doi：
更新日期：1992-05-01 00:00:00
abstract：:Herein we provide evidence for the coexpression of two distinct prostacyclin (PGI(2)) receptors (IP) on BEAS-2B human airway epithelial cells. IP receptor heterogeneity initially was suggested by the finding that the rank orders of potency of PGI(2) and three structurally similar analogs [taprostene, iloprost, 15-deox...
journal_title：Molecular pharmacology
pub_type： 杂志文章
doi：10.1124/mol.110.069674
更新日期：2011-03-01 00:00:00
abstract：:The exchange of tritium into water from saxitoxin molecules that were radiolabeled at the C-11 methylene position was measured at 37 degrees in solution and in suspensions of brain membranes. High concentrations of membrane receptors were used to assure that more than 80% of the total saxitoxin (STX) present was speci...
journal_title：Molecular pharmacology
pub_type： 杂志文章
doi：
更新日期：1982-03-01 00:00:00
abstract：:Dynamin is a GTPase enzyme involved in membrane constriction and fission during endocytosis. Phospholipid binding via its pleckstrin homology domain maximally stimulates dynamin activity. We developed a series of surface-active small-molecule inhibitors, such as myristyl trimethyl ammonium bromide (MiTMAB) and octadec...
journal_title：Molecular pharmacology
pub_type： 杂志文章
doi：10.1124/mol.107.034207
更新日期：2007-12-01 00:00:00
abstract：:Direct gastric mucosal cell damage mediated by nonsteroidal anti-inflammatory drugs (NSAIDs) is involved in the formation of NSAID-induced gastric lesions. We recently suggested that this direct cytotoxicity of NSAIDs is caused by their membrane-permeabilization activity. Geranylgeranylacetone (GGA), a clinically used...
journal_title：Molecular pharmacology
pub_type： 杂志文章
doi：10.1124/mol.105.015784
更新日期：2005-10-01 00:00:00
abstract：:Mouse embryonic spinal cord neurons in culture exhibit spontaneous calcium oscillations from day in vitro (DIV) 6 through DIV 10. Such spontaneous activity in developing spinal cord contributes to maturation of synapses and development of pattern-generating circuits. Here we demonstrate that these calcium oscillations...
journal_title：Molecular pharmacology
pub_type： 杂志文章
doi：10.1124/mol.111.071456
更新日期：2011-06-01 00:00:00
abstract：:This study demonstrates the presence of a novel endothelin (ET) receptor subtype that displays high affinity for both ETA- and ETB-selective ligands. This subtype has been identified in canine spleen membranes using ETB-selective agonists ET-3, IRL-1620, sarafotoxin 6c (S6c) as well as ETA-selective antagonists BQ123 ...
journal_title：Molecular pharmacology
pub_type： 杂志文章
doi：10.1124/mol.52.4.582
更新日期：1997-10-01 00:00:00
abstract：:Five separate guanine nucleotide-binding proteins (G proteins) were immunologically identified in membranes from neuroblastoma x glioma NG108-15 hybrid cells. These alpha subunit proteins were Gi2 alpha, two isoforms of Gi3 alpha, and two isoforms of Go alpha. The G proteins that interacted with delta-opioid receptors...
journal_title：Molecular pharmacology
pub_type： 杂志文章
doi：
更新日期：1992-05-01 00:00:00
abstract：:α-Conotoxins are subtype-selective nicotinic acetylcholine receptor (nAChR) antagonists. Although potent α3β2 nAChR-selective α-conotoxins have been identified, currently characterized α-conotoxins show no or only weak affinity for α4β2 nAChRs, which are, besides α7 receptors, the most abundant nAChRs in the mammalian...
journal_title：Molecular pharmacology
pub_type： 杂志文章
doi：10.1124/mol.112.078683
更新日期：2012-10-01 00:00:00
abstract：:[3H]P1075 binding to membrane preparations of rabbit skeletal muscle were observed in the presence of nucleotide triphosphates or diphosphates but not AMP, cAMP, adenosine, tripolyphosphate, or pyrophosphate. Nonhydrolyzable or poorly hydrolyzable ATP analogs inhibited MgATP-supported binding. The EC50 value for MgATP...
journal_title：Molecular pharmacology
pub_type： 杂志文章
doi：10.1124/mol.52.3.473
更新日期：1997-09-01 00:00:00
abstract：:The effect of ethanol on intracellular ionized calcium concentrations (Cai) was studied in synaptosomes isolated from mouse whole brain and in hepatocytes isolated from rat liver. The fluorescent calcium chelator, fura-2, was used to quantitate Cai. Incubation of synaptosomes with ethanol (350-700 mM) increased restin...
journal_title：Molecular pharmacology
pub_type： 杂志文章
doi：
更新日期：1987-12-01 00:00:00
abstract：:In mammals, receptors for the inhibitory neurotransmitter gamma-aminobutyric acid (GABA) are divided into three pharmacological classes, which are denoted GABAA, GABAB, and GABAC. GABAC receptors are defined by their insensitivity to the GABAA receptor antagonist bicuculline and the GABAB receptor agonist (-)-baclofen...
journal_title：Molecular pharmacology
pub_type： 杂志文章
doi：
更新日期：1996-10-01 00:00:00
abstract：:Binding equilibria of 12 nonsteroidal, anti-inflammatory substances, salicylic acid, diflunisal, phenylbutazone, azapropazone, fenbufen, biphenylacetic acid, naproxen, flurbiprofen, ibuprofin, diclofenac, indomethacin, and benoxaprofen, to defatted human serum albumin has been investigated at 37 degrees, pH 7.4, in a ...
journal_title：Molecular pharmacology
pub_type： 杂志文章
doi：
更新日期：1984-01-01 00:00:00
abstract：:To determine the structural basis for binding subtype selective agonists in the beta-adrenergic receptor (beta AR), we examined the interaction of the mutant beta 2AR and chimeric beta 1/beta 2AR with a selective beta 2AR agonist, TA-2005 (8-hydroxy-5-[(1R)-1-hydroxy-2-[N-[(1R)-2-(p-methoxyphenyl)-1-methyle thy l] am...
journal_title：Molecular pharmacology
pub_type： 杂志文章
doi：10.1124/mol.53.1.128
更新日期：1998-01-01 00:00:00
abstract：:Tumor cell resistance to anthracyclines and epipodophyllotoxins can be due to reduced drug accumulation and/or alterations in the activity of topoisomerase II (TOPO II). HL-60 cells selected in 0.05 micrograms/ml doxorubicin (DOX) are 10-fold and > 20-fold resistant to DOX and etoposide (VP-16), respectively. The accu...
journal_title：Molecular pharmacology
pub_type： 杂志文章
doi：
更新日期：1996-08-01 00:00:00
abstract：:The carbonic anhydrase (CA) isozyme (IV) in microsomes is thought to have a dominant role in secretory processes. Using microsomes from bovine kidney and lung (which had the same activity), we have measured the Km and kcat for CO2 hydration and compared these numbers with those for CA I (red blood cells and gut), CA I...
journal_title：Molecular pharmacology
pub_type： 杂志文章
doi：
更新日期：1993-10-01 00:00:00
abstract：:The isoprenoid donor for protein geranylgeranylation reactions, geranylgeranyl diphosphate (GGDP), is the product of the enzyme GGDP synthase (GGDPS) that condenses farnesyl diphosphate (FDP) and isopentenyl pyrophosphate. GGDPS inhibition is of interest from a therapeutic perspective for multiple myeloma because we h...
journal_title：Molecular pharmacology
pub_type： 杂志文章
doi：10.1124/mol.116.107326
更新日期：2017-03-01 00:00:00
