Abstract:
:Reversible binding of warfarin to defatted serum albumin was studied by equilibrium dialysis at pH 7.4, in a 66 mM sodium phosphate buffer at 37 degrees. The binding isotherm could be described by two stoichiometric binding constants, K1 in the range 141,000 to 192,000 M-1 and K2 at 39,000 to 57,000 M-1. At least two additional molecules could be bound but gave indeterminate binding constants. The product K3 X K4 was about 4.7 X 10(7) M-2. Different site models were possible, either one high affinity and several low affinity sites, or two high affinity sites, cooperative, independent, or anticooperative, together with two low affinity sites. Binding affinity for the first warfarin molecule did not vary with pH in the interval from 6 to 9. The affinity decreased with increasing concentrations of sodium sulfate, sodium chloride, and calcium chloride, depending upon ionic strength. Specific effects of chloride and calcium ions were not observed. Light absorption spectra indicated that the warfarin anion was bound to albumin. All observations were consistent with a binding process involving albumin and the warfarin anion, without participation of hydrogen ions and not influenced by the N-B conformational transition of albumin.
journal_name
Mol Pharmacoljournal_title
Molecular pharmacologyauthors
Larsen FG,Larsen CG,Jakobsen P,Brodersen Rsubject
Has Abstractpub_date
1985-02-01 00:00:00pages
263-70issue
2eissn
0026-895Xissn
1521-0111journal_volume
27pub_type
杂志文章abstract::We have studied the mechanism of action of Arg(*)-Arg-Nal(2)-Cys(1x)-Tyr-Gln-Lys-(d-Pro)-Pro-Tyr-Arg-Cit-Cys(1x)-Arg-Gly-(d-Pro)(*) (POL3026), a novel specific beta-hairpin mimetic CXC chemokine receptor (CXCR)4 antagonist. POL3026 specifically blocked the binding of anti-CXCR4 monoclonal antibody 12G5 and the intrace...
journal_title:Molecular pharmacology
pub_type: 杂志文章
doi:10.1124/mol.107.042911
更新日期:2008-04-01 00:00:00
abstract::The cDNAs for the four murine aryl hydrocarbon (Ah) receptor alleles were cloned and sequenced, and the deduced amino acid sequences were compared. The Ahb-1 allele encodes a protein of 805 amino acids, the Ahd and Ahb-2 alleles encode proteins of 848 amino acids, and the Ahb-3 allele encodes a protein of 883 amino ac...
journal_title:Molecular pharmacology
pub_type: 杂志文章
doi:
更新日期:1994-11-01 00:00:00
abstract::The chelator di-2-pyridylketone 4,4-dimethyl-3-thiosemicarbazone (Dp44mT) shows potent and selective anticancer and antimetastatic activity. However, the mechanism by which it is initially transported into cells to induce cytotoxicity is unknown. Hence, the current investigation examined the cellular uptake of ¹⁴C-Dp4...
journal_title:Molecular pharmacology
pub_type: 杂志文章
doi:10.1124/mol.113.088393
更新日期:2013-12-01 00:00:00
abstract::Of four monoclonal antibodies to purified rat liver cytochrome P450s, including those from 3-methylcholanthrene-, phenobarbital-, ethanol-, and pregnenolone-16-alpha-carbonitrile-treated rats, only the monoclonal antibody against pregnenolone-16-alpha-carbonitrile-inducible P450 immunodetected proteins in chicken live...
journal_title:Molecular pharmacology
pub_type: 杂志文章
doi:
更新日期:1989-05-01 00:00:00
abstract::Thrombin, the key effector protease of the coagulation cascade, drives fibrin deposition and activates human platelets through protease-activated receptor-1 (PAR1). These processes are critical to the progression of thrombotic diseases. Thrombin is the main target of anticoagulant therapy, and major efforts have led t...
journal_title:Molecular pharmacology
pub_type: 杂志文章
doi:10.1124/mol.114.096446
更新日期:2015-07-01 00:00:00
abstract::The metabotropic glutamate receptor subtype 5 (mGlu5) activates calcium mobilization via binding of glutamate, the major excitatory neurotransmitter in the central nervous system. Allosteric modulation of the receptor has recently emerged as a promising alternative method of regulation to traditional regulation throug...
journal_title:Molecular pharmacology
pub_type: 杂志文章
doi:10.1124/mol.105.016139
更新日期:2005-12-01 00:00:00
abstract::The mechanisms underlying mastoparan-induced elevation of the intracellular free calcium concentration ([Ca2+]i) were investigated in the insulin-secreting cell lines RINm5F and HIT. In both cell types, micromolar concentrations of mastoparan induced a prompt increase of [Ca2+]i, measured as an increase in fura-2 fluo...
journal_title:Molecular pharmacology
pub_type: 杂志文章
doi:
更新日期:1995-04-01 00:00:00
abstract::Membrane trafficking of the δ-opioid receptor (DOR) from intracellular compartments to plasma membrane in central neurons, induced by various pathological conditions such as long-term opioid exposure, represents unique receptor plasticity involved in the mechanisms of long-term opioid effects in opioid addiction and o...
journal_title:Molecular pharmacology
pub_type: 杂志文章
doi:10.1124/mol.111.076307
更新日期:2012-03-01 00:00:00
abstract::Histone deacetylase inhibitors (HDACi), which have emerged as a new class of anticancer agents, act by modulating expression of genes controlling apoptosis or cell proliferation. Here, we compared the effect of HDACi on transcriptional activation by estrogen or glucocorticoid receptors (ER and GR, respectively), two m...
journal_title:Molecular pharmacology
pub_type: 杂志文章
doi:10.1124/mol.105.014514
更新日期:2005-12-01 00:00:00
abstract::Arrestins mediate G protein-coupled receptor desensitization, internalization, and signaling. Dopamine D(2) and D(3) receptors have similar structures but distinct characteristics of interaction with arrestins. The goals of this study were to compare arrestin-binding determinants in D(2) and D(3) receptors other than ...
journal_title:Molecular pharmacology
pub_type: 杂志文章
doi:10.1124/mol.108.050534
更新日期:2009-01-01 00:00:00
abstract::Activation of endothelial nitric-oxide synthase (eNOS) has been shown to occur through various pathways involving increases in the cytosolic Ca(2+) concentration, activation of the phosphatidylinositol-3' kinase/Akt pathway, as well as regulation by other kinases and by protein-protein interactions. We have recently r...
journal_title:Molecular pharmacology
pub_type: 杂志文章
doi:10.1124/mol.63.4.886
更新日期:2003-04-01 00:00:00
abstract::Two different mechanisms leading to increased current have been described for the small-molecule human ether-à-go-go-related gene (herg) activator NS1643 [1,3-bis-(2-hydroxy-5-trifluoromethylphenyl)-urea]. On herg1a channels expressed in Xenopus laevis oocytes, it mainly acts via attenuation of inactivation and for ra...
journal_title:Molecular pharmacology
pub_type: 杂志文章
doi:10.1124/mol.111.071621
更新日期:2011-11-01 00:00:00
abstract::Combinations of coimmunoprecipitation, single-cell fluorescence resonance energy transfer, and cell-surface time-resolved fluorescence resonance energy transfer demonstrated protein-protein interactions and quaternary structure for the alpha(1b)-adrenoceptor. Self-association of transmembrane domain 1 and its interact...
journal_title:Molecular pharmacology
pub_type: 杂志文章
doi:10.1124/mol.104.001586
更新日期:2004-11-01 00:00:00
abstract::Kinetics of the interactions between the neuromuscular blocker alcuronium, the specific muscarinic antagonist N-[methyl-3H] methyl scopolamine ([3H]NMS), and muscarinic receptors were investigated in homogenates of rat heart atria. Two effects of alcuronium on the binding of [3H]NMS could be distinguished. (a) Alcuron...
journal_title:Molecular pharmacology
pub_type: 杂志文章
doi:
更新日期:1994-04-01 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
pub_type: 杂志文章
doi:10.1124/mol.111.074138
更新日期:2011-12-01 00:00:00
abstract::Retroviral integrases are essential for viral replication and represent an attractive chemotherapeutic target. In the current study, we demonstrated the activity of micromolar concentrations of dinucleotides against human immunodeficiency virus type 1 (HIV-1), HIV type 2 (HIV-2), simian immunodeficiency virus, and fel...
journal_title:Molecular pharmacology
pub_type: 杂志文章
doi:10.1124/mol.51.4.567
更新日期:1997-04-01 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
pub_type: 杂志文章
doi:10.1124/mol.109.055665
更新日期:2009-09-01 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::Seven transmembrane G protein-coupled receptors (GPCRs) are often phosphorylated at the C terminus and on intracellular loops in response to various extracellular stimuli. Phosphorylation of GPCRs by GPCR kinases and certain other kinases can promote the recruitment of arrestin molecules. The arrestins critically regu...
journal_title:Molecular pharmacology
pub_type: 杂志文章,评审
doi:10.1124/mol.116.107839
更新日期:2017-09-01 00:00:00
abstract::It is widely accepted that cAMP signaling is compartmentalized within cells. However, our knowledge of how receptors, cAMP signaling enzymes, effectors, and other key proteins form specific signaling complexes to regulate specific cell responses is limited. The multicomponent nature of these systems and the spatiotemp...
journal_title:Molecular pharmacology
pub_type: 杂志文章,评审
doi:10.1124/mol.117.110825
更新日期:2018-04-01 00:00:00
abstract::Merbarone (5-[N-phenyl carboxamido]-2-thiobarbituric acid) is an anticancer drug that inhibits the catalytic activity of DNA topoisomerase II (topo II) without damaging DNA or stabilizing DNA-topo II cleavable complexes. Although the cytotoxicity of the complex-stabilizing DNA-topo II inhibitors such as VP-16 (etoposi...
journal_title:Molecular pharmacology
pub_type: 杂志文章
doi:
更新日期:1999-03-01 00:00:00
abstract::Valproic acid (VPA) is an effective antiepileptic drug with an additional activity for the treatment of bipolar disorder. It has been assumed that both activities arise from a common target. At the molecular level, VPA targets a number of distinct proteins that are involved in signal transduction. VPA inhibition of in...
journal_title:Molecular pharmacology
pub_type: 杂志文章
doi:10.1124/mol.106.030601
更新日期:2007-03-01 00:00:00
abstract::Nuclear receptors play important roles in the maintenance of the endocrine system, regulation of organ differentiation, and fetal development. Endocrine disruptors exert their adverse effects by disrupting the endocrine system via various mechanisms. To assess the effects of endocrine disruptors on nuclear receptors, ...
journal_title:Molecular pharmacology
pub_type: 杂志文章
doi:10.1124/mol.104.008409
更新日期:2005-03-01 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
pub_type: 杂志文章
doi:10.1124/mol.113.091249
更新日期:2014-05-01 00:00:00
abstract::An 'epoxygenase' eicosanoid analog, 14, 15-cis-episulfide-eicosatrienoic acid, has several unique pharmacological effects on platelets. These include (i) inhibition of ionophore A23187- but not thrombin-induced activation, (ii) inhibition of thromboxane B2 biosynthesis derived from endogenous but not exogenous arachid...
journal_title:Molecular pharmacology
pub_type: 杂志文章
doi:
更新日期:1991-02-01 00:00:00
abstract::Guinea pig lung microsomes converted arachidonic acid (AA) to two classes of cytochrome P450 (P450)-dependent metabolites, 16- through 20-hydroxyeicosatetraenoic acids [(16-20)-OH-AA] and epoxyeicosatrienoic acids (EETs). The rate of formation of (16-20)-OH-AA was approximately 3-fold higher in microsomes from beta-na...
journal_title:Molecular pharmacology
pub_type: 杂志文章
doi:
更新日期:1994-06-01 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::The chemotherapeutic anthracycline metabolite doxorubicinol (doxOL) has been shown to interact with and disrupt the function of the cardiac ryanodine receptor Ca2+ release channel (RyR2) in the sarcoplasmic reticulum (SR) membrane and the SR Ca2+ binding protein calsequestrin 2 (CSQ2). Normal increases in RyR2 activit...
journal_title:Molecular pharmacology
pub_type: 杂志文章
doi:10.1124/mol.117.108183
更新日期:2017-11-01 00:00:00
abstract::The catestatin fragment of chromogranin A is an endogenous inhibitor of nicotinic cholinergic transmission, functioning in negative feedback control of catecholamine secretion. We explored naturally occurring polymorphisms in the amino acid sequence of catestatin. Three human variants were identified: Gly364Ser, Pro37...
journal_title:Molecular pharmacology
pub_type: 杂志文章
doi:10.1124/mol.104.002139
更新日期:2004-11-01 00:00:00
abstract::Nitric oxide (NO) promotes retinal and choroidal neovascularization, although different isoforms of nitric-oxide synthetase (NOS) are critical in each. Deficiency of endothelial NOS (eNOS) suppresses retinal but not choroidal neovascularization, whereas deficiency of neuronal NOS (nNOS) or inducible NOS (iNOS) suppres...
journal_title:Molecular pharmacology
pub_type: 杂志文章
doi:10.1124/mol.62.3.539
更新日期:2002-09-01 00:00:00