Abstract：
:The effect of the thiol-alkylating agent, N-ethylmaleimide (NEM), on histamine (HA) H1-receptors from guinea pig cerebellum, labeled with [3H]mepyramine, was investigated. The properties of [3H]mepyramine binding (apparent dissociation constant and maximal number of sites) were not modified by prior treatment of the membranes with 2 or 5 mM NEM. This treatment did not change either the inhibition curves of d-chlorpheniramine or mianserin, two H1-receptor antagonists. In contrast, treatments of membranes with NEM significantly decreased the IC50 values of HA and the slope indexes (pseudo Hill coefficients) of HA inhibition curves, which became inferior to unity. These effects were irreversible, and their extent related to the NEM treatment duration and the NEM concentration. A computer analysis of the data indicated that part of the H1-receptors were converted from a state of low affinity for the amine (IC50 value of 75 microM) into a high agonist affinity state (IC50 value of 2 microM). The change was less marked for partial agonists than for HA. The NEM-induced change was observed in the presence and in the absence of Na+ ions, known to decrease the affinity of HA for H1-receptors. Agonists or antagonists did not protect against the modification of HA affinity induced by NEM. The digitonin-solubilized receptors retained their sensitivity to NEM. Among other thiol reagents, iodoacetamide and iodoacetic acid were ineffective, and organic mercurial agents strongly reduced the number of [3H]mepyramine-binding sites. NEM treatment might alkylate a critical thiol group located outside the ligand-binding domain of the H1 receptor and thereby stabilize the latter in a conformation distinct from that of the activated state.
journal_name
Mol Pharmacoljournal_title
Molecular pharmacologyauthors
Yeramian E,Garbarg M,Schwartz JCsubject
Has Abstractpub_date
1985-08-01 00:00:00pages
155-62issue
2eissn
0026-895Xissn
1521-0111journal_volume
28pub_type
杂志文章abstract：:The phosphatidylcholine-using phospholipase D (PLD) isoform PLD2 is widely expressed in mammalian cells and is activated in response to a variety of promitogenic agonists. In this study, active and inactive hemagglutinin-tagged human PLD2 (HA-PLD2) constructs were stably expressed in an EL4 cell line lacking detectabl...
journal_title：Molecular pharmacology
pub_type： 杂志文章
doi：10.1124/mol.107.040105
更新日期：2008-09-01 00:00:00
abstract：:The ligand specificity of rat adenohypophyseal vasopressin receptors was directly compared to that of peripheral receptors of the V1 and V2 types. For this purpose a series of 15 recently designed vasopressin antagonists was used. The affinities of these antagonists for rat adenohypophyseal membranes were deduced from...
journal_title：Molecular pharmacology
pub_type： 杂志文章
doi：
更新日期：1986-08-01 00:00:00
abstract：:Past decades of cancer research have mainly focused on the role of various extracellular and intracellular biochemical signals on cancer progression and metastasis. Recent studies suggest an important role of mechanical forces in regulating cellular behaviors. This review first provides an overview of the mechanobiolo...
journal_title：Molecular pharmacology
pub_type： 杂志文章,评审
doi：10.1124/mol.116.106765
更新日期：2016-12-01 00:00:00
abstract：:The CB1 cannabinoid receptor has been implicated in the regulation of bone remodeling and bone mass. A high bone mass (HBM) phenotype was reported in CB1-null mice generated on a CD1 background (CD1(CB1-/-) mice). By contrast, our preliminary studies in cb1-/- mice, backcrossed to C57BL/6J mice (C57(CB1-/-) mice), rev...
journal_title：Molecular pharmacology
pub_type： 杂志文章
doi：10.1124/mol.106.026435
更新日期：2006-09-01 00:00:00
abstract：:High-affinity glycine transport in neurons and glial cells is a primary means of inactivating synaptic glycine. We have synthesized a potent selective inhibitor of glycine transporter 1 (GlyT1), and characterized its activity using a quail fibroblast cell line (QT6). The glycine transporters GlyT1A, GlyT1B, GlyT1C, an...
journal_title：Molecular pharmacology
pub_type： 杂志文章
doi：10.1124/mol.60.6.1414
更新日期：2001-12-01 00:00:00
abstract：:We examined the effects on allosteric modulation and ligand binding of the mutation of amino acid residues of the human A(3) adenosine receptor (A(3)AR) that are hypothesized to be near one of three loci: the putative sodium binding site, the putative ligand binding site, and the DRY motif in transmembrane helical dom...
journal_title：Molecular pharmacology
pub_type： 杂志文章
doi：10.1124/mol.63.5.1021
更新日期：2003-05-01 00:00:00
abstract：:Camptothecin (CPT) is an effective chemotherapeutic agent for treatment of patients with cancer. The mechanisms underlying CPT-mediated responses in cancer cells are not fully understood. MicroRNA (miRNA) play important roles in tumorigenesis and drug sensitivity. However, the interaction between camptothecin and miRN...
journal_title：Molecular pharmacology
pub_type： 杂志文章
doi：10.1124/mol.111.076794
更新日期：2012-04-01 00:00:00
abstract：:Controlled inhibition of brain acetyl- and butyrylcholinesterases (AChE and BChE, respectively) and of monoamine oxidase-B (MAO-B) may slow neurodegeneration in Alzheimer's and Parkinson's diseases. It was postulated that certain carbamate esters would inhibit AChE and BChE with the concomitant release in the brain of...
journal_title：Molecular pharmacology
pub_type： 杂志文章
doi：10.1124/mol.107.033928
更新日期：2007-06-01 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：: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：:Thiopurine methyltransferase (TPMT) catalyzes the S-methylation of thiopurine drugs such as 6-mercaptopurine. Levels of TPMT activity in human tissue are controlled by a common genetic polymorphism that is an important factor responsible for individual variation in thiopurine drug toxicity and therapeutic efficacy. Ou...
journal_title：Molecular pharmacology
pub_type： 杂志文章
doi：
更新日期：1993-06-01 00:00:00
abstract：:Large-conductance Ca(2+)-activated K(+) (BK(Ca)) channels encoded by the Slo1 gene are ubiquitously expressed, and they play a role in regulation of many cell types. In excitable cells, BK(Ca) channels and voltage-activated Ca(2+) channels often form functional complexes that allow the cytoplasmic domains of BK(Ca) ch...
journal_title：Molecular pharmacology
pub_type： 杂志文章
doi：10.1124/mol.107.040733
更新日期：2008-02-01 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：:Some biochemical and pharmacological properties of a novel, potent inhibitor of cyclic AMP phosphodiesterase, N-cyclohexyl-N-methyl-4-(7-oxy-1,2,3,5-tetrahydroimidazo[2,1-b] quinazolin-2-one) butyramide (RS-82856), were investigated. RS-82856 selectively inhibits the high affinity form of cyclic AMP phosphodiesterase ...
journal_title：Molecular pharmacology
pub_type： 杂志文章
doi：
更新日期：1986-06-01 00:00:00
abstract：:In saturation studies with [3H]dihydromorphine, unlabeled D-Ala2-D-Leu5-enkephalin (1 nM) inhibited the high-affinity binding component far more potently than the lower-affinity one. Similarly, morphine (1 nM) inhibited the higher-affinity binding of 3H-D-Ala2-D-Leu5-enkephalin to a greater extent than its lower-affin...
journal_title：Molecular pharmacology
pub_type： 杂志文章
doi：
更新日期：1984-01-01 00:00:00
abstract：:Folate receptor-targeted cancer therapies constitute a promising treatment for the approximately one third of human cancers that overexpress the folate receptor (FR). However, the potencies of all folate-receptor targeted therapies depend on 1) the rate of folate-linked drug conjugate binding to the cancer cell surfac...
journal_title：Molecular pharmacology
pub_type： 杂志文章
doi：10.1124/mol.104.003723
更新日期：2004-12-01 00:00:00
abstract：:Rapid activation of guanine nucleotide-binding protein (G protein)-mediated signal transduction mechanisms occurs in many tissues. The human neutrophil provides a useful model for studying the mechanisms of these fast processes. Fluorescent chemotactic tetrapeptide and pentapeptide exhibit 30-50% quenching of fluoresc...
journal_title：Molecular pharmacology
pub_type： 杂志文章
doi：
更新日期：1993-05-01 00:00:00
abstract：:The human caudate and putamen contain two high affinity binding sites for [3H]spiroperidol. Both of these affinity states exhibit dopaminergic selectivity. Ascorbic acid, at 0.1 mM, induces a slow loss of the low affinity component of [3H]spiroperidol binding in these tissues. The addition of guanyl nucleotides to the...
journal_title：Molecular pharmacology
pub_type： 杂志文章
doi：
更新日期：1988-02-01 00:00:00
abstract：:Iron-loading diseases remain an important problem because of the toxicity of iron-catalyzed redox reactions. Iron loading occurs in the mitochondria of Friedreich's ataxia (FA) patients and may play a role in its pathogenesis. This suggests that iron chelation therapy could be useful. We developed previously the lipop...
journal_title：Molecular pharmacology
pub_type： 杂志文章
doi：10.1124/mol.108.046847
更新日期：2008-07-01 00:00:00
abstract：:(6R)-5,6,7,8-Tetrahydrobiopterin (BH4), which is synthesized intracellularly from GTP, caused a concentration-dependent increase in rat pheochromocytoma (PC12) cell proliferation when added exogenously. Incubation with sepiapterin, which is converted enzymatically to BH4 within cells, also increased PC12 cell prolifer...
journal_title：Molecular pharmacology
pub_type： 杂志文章
doi：
更新日期：1996-01-01 00:00:00
abstract：:The functional significance of the conserved amino acids within transmembrane regions II and VII of the human 5-hydroxytryptamine (5-HT)1A receptor was analyzed by oligonucleotide-directed mutagenesis followed by transient expression of the mutated receptor genes in COS-1 cells. The substitution of a conserved asparag...
journal_title：Molecular pharmacology
pub_type： 杂志文章
doi：
更新日期：1993-04-01 00:00:00
abstract：:Guanine nucleotides have been examined as to their effects on subclass-specific excitatory amino acid receptor-ligand interactions. Guanine nucleotides selectively inhibit L-[3H]glutamate binding to the N-methyl-D-aspartate (NMDA) recognition site while showing a lesser effect on [3H]kainate, [3H]alpha-amino-3-hydroxy...
journal_title：Molecular pharmacology
pub_type： 杂志文章
doi：
更新日期：1988-08-01 00:00:00
abstract：:The Gαi/o-coupled dopamine D2-like receptor family comprises three subtypes: the D2 receptor (D2R), with short and long isoform variants (D2SR and D2LR), D3 receptor (D3R), and D4 receptor (D4R), with several polymorphic variants. The common overlap of norepinephrine innervation and D2-like receptor expression pattern...
journal_title：Molecular pharmacology
pub_type： 杂志文章
doi：10.1124/mol.115.101808
更新日期：2016-04-01 00:00:00
abstract：:The ability of dopamine agonists and antagonists to compete with [3H]spiperone binding to rat striatal membrane preparations at 4, 15, 26, and 37 degrees varied markedly with temperature. Dopamine and the dopamine agonist 2-amino-6,7-dihydroxy-1,2,3,4-tetrahydronaphthalene hydrobromide (ADTN) were more potent at lower...
journal_title：Molecular pharmacology
pub_type： 杂志文章
doi：
更新日期：1986-09-01 00:00:00
abstract：:Peroxisome proliferator-activated receptor δ (PPARδ) has been implicated in vascular pathophysiology. However, its functions in atherogenic changes of the vascular wall have not been fully elucidated. PPARδ activated by GW501516 (2-[2-methyl-4-[[4-methyl-2-[4-(trifluoromethyl)phenyl]-1,3-thiazol-5-yl]methylsulfanyl]ph...
journal_title：Molecular pharmacology
pub_type： 杂志文章
doi：10.1124/mol.116.104679
更新日期：2016-11-01 00:00:00
abstract：:The local anesthetic-like Na+ channel-blocking drug [3H]PD85639 [alpha-([4-3H]phenyl)-N-[3-(2,6-dimethyl-1-piperizinyl)-alpha-prop yl] [4-3H]benzeneacetamide] binds specifically to receptor sites on Na+ channels in intact synaptosomes and synaptosomal membranes, purified and reconstituted Na+ channels, and type IIA Na...
journal_title：Molecular pharmacology
pub_type： 杂志文章
doi：
更新日期：1993-06-01 00:00:00
abstract：:We have previously identified allosteric modulators of the cannabinoid CB(1) receptor (Org 27569, PSNCBAM-1) that display a contradictory pharmacological profile: increasing the specific binding of the CB(1) receptor agonist [(3)H]CP55940 but producing a decrease in CB(1) receptor agonist efficacy. Here we investigate...
journal_title：Molecular pharmacology
pub_type： 杂志文章
doi：10.1124/mol.112.080879
更新日期：2013-02-01 00:00:00
abstract：:Two human ovarian cancer cell lines were established from a patient before (PEO1) and after (PEO4) the onset of resistance to 5-fluorouracil (5-FU)/cisplatin-based chemotherapy. Using growth inhibition assays, we determined that the PEO4 line was almost 5-fold more resistant to 5-FU than the PEO1 line. The addition of...
journal_title：Molecular pharmacology
pub_type： 杂志文章
doi：
更新日期：1990-09-01 00:00:00
abstract：:Sulfation, catalyzed by members of the sulfotransferase (SULT) superfamily, exerts considerable influence over the biological activity of numerous endogenous and xenobiotic chemicals. In humans, catecholamines such as dopamine are extensively sulfated, and a SULT isoform (SULT1A3 or the monoamine-sulfating form of phe...
journal_title：Molecular pharmacology
pub_type： 杂志文章
doi：10.1124/mol.54.6.942
更新日期：1998-12-01 00:00:00
abstract：:The Notch family consists of four highly conserved transmembrane receptors. The release of the active intracellular domain requires the enzymatic activity of γ-secretase. Notch is involved in embryonic development and in many physiologic processes of normal cells, in which it regulates growth, apoptosis, and different...
journal_title：Molecular pharmacology
pub_type： 杂志文章,评审
doi：10.1124/molpharm.120.000006
更新日期：2020-11-01 00:00:00
