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 sodium phosphate buffer, 66 mM, by means of equilibrium dialysis and, in case of salicylic acid, by dialysis rate determinations. Cobinding of each of these drugs with monoacetyl-4,4'-diaminodiphenyl sulfone, warfarin, and diazepam has been studied by measuring dialysis rates of the last-mentioned ligands. Cobinding of each drug with bilirubin was investigated by two techniques, equilibrium dialysis against albumin with and without bilirubin, and by measuring rates of oxidation of free bilirubin with hydrogen peroxide and peroxidase. Results were analyzed in quantitative terms. The use of a site-oriented description versus a stoichiometric analysis is discussed. The stoichiometric description is preferred for the following reasons: (a) Simple relations exist between the percentage of bound drug at low drug concentrations and the first stoichiometric binding constant. (b) The stoichiometric description does not imply that preformed binding sites are present in the albumin molecule. (c) A quantitative, stoichiometric analysis of multiple cobinding of two ligands is possible.
journal_name
Mol Pharmacoljournal_title
Molecular pharmacologyauthors
Honoré B,Brodersen Rsubject
Has Abstractpub_date
1984-01-01 00:00:00pages
137-50issue
1eissn
0026-895Xissn
1521-0111journal_volume
25pub_type
杂志文章abstract：:Hepatic CYP2E1 is induced in several models of alcohol administration, but clinically relevant pathology is only observed in rats in a model involving the continuous intragastric administration of an ethanol-containing, corn oil-based, high-fat diet. The level of CYP2E1 correlates with the degree of liver pathology in...
journal_title：Molecular pharmacology
pub_type： 杂志文章
doi：10.1124/mol.51.6.944
更新日期：1997-06-01 00:00:00
abstract：:The carbocyclic analogue of 5-nitro-2'-deoxyuridine (NO2dUrd), in which the sugar moiety is replaced by a cyclopentane ring and which was designated C-NO2dUrd, has been evaluated for its cytostatic, antimetabolic, and antitumor properties. The following findings are noted. C-NO2dUrd is about 500- to 2000-fold less inh...
journal_title：Molecular pharmacology
pub_type： 杂志文章
doi：
更新日期：1985-05-01 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
pub_type： 杂志文章,评审
doi：10.1124/mol.104.002261
更新日期：2004-11-01 00:00:00
abstract：:Olanzapine was shown to be oxidized to a reactive intermediate by HOCl, which is the major oxidant produced by activated neutrophils. A mass spectrum obtained using a flow system in which the reactants were fed into a mixing chamber and the products flowed directly into a mass spectrometer revealed a reactive intermed...
journal_title：Molecular pharmacology
pub_type： 杂志文章
doi：
更新日期：1998-06-01 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
pub_type： 杂志文章
doi：10.1124/mol.104.001966
更新日期：2004-09-01 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
pub_type： 杂志文章
doi：
更新日期：1984-09-01 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：:Human cytochrome P450 (CYP) 2C enzymes metabolize ∼30% of clinically prescribed drugs and various environmental chemicals. CYP2C8, an important member of this subfamily, metabolizes the anticancer drug paclitaxel, certain antidiabetic drugs, and endogenous substrates, including arachidonic acid, to physiologically act...
journal_title：Molecular pharmacology
pub_type： 杂志文章
doi：10.1124/mol.115.100255
更新日期：2016-01-01 00:00:00
abstract：:The aim of this study was to use pharmacological inhibition of protein kinase A and mutation of potential protein kinase A phosphorylation sites to determine the role of protein kinase A-catalyzed phosphorylation of the dopamine D(1) receptor in agonist-stimulated desensitization and internalization of the receptor. T...
journal_title：Molecular pharmacology
pub_type： 杂志文章
doi：10.1124/mol.61.4.806
更新日期：2002-04-01 00:00:00
abstract：:The sympathetic nervous system modulates cardiac contractility and rate by activating beta-adrenergic receptors (beta AR) expressed on cardiac myocytes and specialized cells in the sinoatrial node and the conduction system. Recent clinical studies have suggested that beta-adrenergic receptors also play a role in cardi...
journal_title：Molecular pharmacology
pub_type： 杂志文章
doi：
更新日期：2001-09-01 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：:PDE4A11 is a novel cAMP-specific phosphodiesterase that is conserved in humans, mouse, rat, pig, and bat. Exon-1(4A11) encodes its unique, 81 amino acid N-terminal region. Reverse-transcriptase polymerase chain reaction performed across the splice junction, plus identification of expressed sequence tags, identifies PD...
journal_title：Molecular pharmacology
pub_type： 杂志文章
doi：10.1124/mol.104.009423
更新日期：2005-06-01 00:00:00
abstract：:A site-directed alkylating agent was used to inactivate one or more types of opioid receptor in two bioassay preparations in the presence of type-selective ligands as protectors of other opioid receptor types. Since the pharmacological potency of an agonist is decreased when the receptor type through which it acts has...
journal_title：Molecular pharmacology
pub_type： 杂志文章
doi：
更新日期：1984-05-01 00:00:00
abstract：:Pharmacological study of rat thalamic gamma-aminobutyric acidA (GABAA) receptors revealed the presence of two distinct populations, namely, diazepam-sensitive and diazepam-insensitive [3H]Ro15-4513 binding sites accounting for 94 +/- 2% (1339 +/- 253 fmol/mg protein) and 6 +/- 2% (90 +/- 44 fmol/mg protein) of total s...
journal_title：Molecular pharmacology
pub_type： 杂志文章
doi：10.1124/mol.56.1.110
更新日期：1999-07-01 00:00:00
abstract：:Regulator of G protein signaling (RGS) proteins are negative modulators of G protein signaling that have emerged as promising drug targets to improve specificity and reduce side effects of G protein-coupled receptor-related therapies. Several small molecule RGS protein inhibitors have been identified; however, enhanci...
journal_title：Molecular pharmacology
pub_type： 杂志文章
doi：10.1124/molpharm.120.000061
更新日期：2020-12-01 00:00:00
abstract：:Receptors for the serine protease thrombin and for lysophospholipids are coupled to G proteins and control a wide range of cellular functions, including mitogenesis. Activators of these receptors are present in blood, and can enter the brain during central nervous system (CNS) injury. Reactive astrogliosis, a prominen...
journal_title：Molecular pharmacology
pub_type： 杂志文章
doi：10.1124/mol.64.5.1199
更新日期：2003-11-01 00:00:00
abstract：:The organic anions picrate (2,4,6-trinitrophenol) and niflumate (2-[[3-(trifluoromethyl)phenyl]-amino]-3-pyridinecarboxylate) were examined for their effects on radioligand binding to the gamma-aminobutyric acid (GABA)/benzodiazepine receptor complex. Neither organic anion produced the enhancement of [35S] t-butylbicy...
journal_title：Molecular pharmacology
pub_type： 杂志文章
doi：
更新日期：1988-12-01 00:00:00
abstract：:We show here that arsenite (As(3+)) elicits multiple effects on gene control, such as the interruption of cell cycle control by initiating G(2)/M arrest as well as inhibiting the aryl hydrocarbon (Ah) receptor-mediated 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD)-inducible expression of CYP1A1. This raises the question ...
journal_title：Molecular pharmacology
pub_type： 杂志文章
doi：10.1124/mol.104.006130
更新日期：2005-04-01 00:00:00
abstract：:The midbrain periaqueductal gray (PAG) is involved in organizing behavioral responses to threat, stress, and pain. These PAG functions are modulated by cholinergic agents. In the present study, we examined the cholinergic modulation of synaptic transmission in the PAG using whole-cell voltage-clamp recordings from rat...
journal_title：Molecular pharmacology
pub_type： 杂志文章
doi：10.1124/mol.108.045872
更新日期：2008-11-01 00:00:00
abstract：:Acute desensitization of mu opioid receptors is thought to be an initial step in the development of tolerance to opioids. Given the resistance of the respiratory system to develop tolerance, desensitization of neurons in the Kölliker-Fuse (KF), a key area in the respiratory circuit, was examined. The activation of G p...
journal_title：Molecular pharmacology
pub_type： 杂志文章
doi：10.1124/mol.117.109603
更新日期：2018-01-01 00:00:00
abstract：:A substantial body of research implicates L-cysteine sulfinic acid (L-CSA) as a neurotransmitter. However, all physiological actions of L-CSA that have been pharmacologically characterized are mediated by cross-activation of glutamate receptors, and no receptor has been identified that is primarily activated by L-CSA....
journal_title：Molecular pharmacology
pub_type： 杂志文章
doi：
更新日期：1994-06-01 00:00:00
abstract：:Magnesium modulates hormone-sensitive adenylate cyclase activation. In the present studies, we have examined the magnesium requirement of beta-adrenergic-stimulated adenylate cyclase activity in permeabilized human lymphocytes. Following isoproterenol pretreatment, under conditions that lead to homologous beta-adrener...
journal_title：Molecular pharmacology
pub_type： 杂志文章
doi：
更新日期：1989-03-01 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
pub_type： 杂志文章
doi：10.1124/mol.110.065102
更新日期：2010-10-01 00:00:00
abstract：:The effect of cyanomorpholinyldoxorubicin, morpholinyldoxorubicin, doxorubicin, and Actinomycin D were studied on purified mouse leukemia (L1210) DNA topoisomerases I and II. DNA unwinding and cross-linking were also studied. It was found that 1) morpholinyldoxorubicin, cyanomorpholinyldoxorubicin, and Actinomycin D (...
journal_title：Molecular pharmacology
pub_type： 杂志文章
doi：
更新日期：1990-07-01 00:00:00
abstract：:Bordetella pertussis, the pathogen responsible for whooping cough, releases a soluble calmodulin-sensitive adenylate cyclase into its culture medium which enters several different types of animal cells and elevates intracellular cAMP. In this study, the influence of B. pertussis adenylate cyclase on intracellular cAMP...
journal_title：Molecular pharmacology
pub_type： 杂志文章
doi：
更新日期：1987-05-01 00:00:00
abstract：:The 5'-flanking region of the mouse mu opioid receptor (MOR) gene has two promoters, referred to as distal and proximal. MOR mRNA is predominantly initiated by the proximal promoter. Previously, several important cis-elements and trans-factors have been shown to play a functional role in the proximal promoter of the M...
journal_title：Molecular pharmacology
pub_type： 杂志文章
doi：10.1124/mol.104.008284
更新日期：2005-05-01 00:00:00
abstract：:ORKAMBI, a combination of the corrector, lumacaftor, and the potentiator, ivacaftor, partially rescues the defective processing and anion channel activity conferred by the major cystic fibrosis-causing mutation, F508del, in in vitro studies. Clinically, the improvement in lung function after ORKAMBI treatment is modes...
journal_title：Molecular pharmacology
pub_type： 杂志文章
doi：10.1124/mol.119.117143
更新日期：2019-10-01 00:00:00
abstract：:Atropine, the classic muscarinic receptor antagonist, inhibits ion currents mediated by neuronal nicotinic acetylcholine receptors expressed in Xenopus laevis oocytes. At the holding potential of -80 mV, 1 microM atropine inhibits 1 mM acetylcholine-induced inward currents mediated by rat alpha2beta2, alpha2beta4, alp...
journal_title：Molecular pharmacology
pub_type： 杂志文章
doi：10.1124/mol.52.5.886
更新日期：1997-11-01 00:00:00
abstract：:The regulation of cellular responsiveness to dopamine via the D2 dopamine receptor was investigated in mouse fibroblast Ltk-cells stably expressing the rat D2-short receptor [Nature (Lond.) 336:783-787 (1988)]. Dopamine inhibited forskolin-stimulated cAMP levels in these cells (half-maximal inhibition at 3.9 +/- 1.1 n...
journal_title：Molecular pharmacology
pub_type： 杂志文章
doi：
更新日期：1991-01-01 00:00:00
abstract：:Four piperazinoquinolone antibacterial drugs (norfloxacin, ciprofloxacin, enoxacin, and pipemidic acid), known to be gamma-aminobutyric acid (GABA) antagonists, fully reversed the inhibitory effect of GABA on [35S]t-butylbicyclophosphorothionate ([35S] TBPS) binding to rat brain membranes in vitro. Twelve indomethacin...
journal_title：Molecular pharmacology
pub_type： 杂志文章
doi：
更新日期：1993-05-01 00:00:00
