Abstract:
:Cultured murine hepatoma 1c1c7 cells were treated with either the actin filament-disrupting drug cytochalasin D or the microtubule inhibitors colchicine and nocadazole (NOC) to assess the role of the cytoskeleton in the process of cytochrome P450 Cyp1a-1 induction. Indirect fluorescence analyses demonstrated that microtubule or actin networks were disrupted within 1 hr of treatment and remained altered as long as cultures were maintained in the presence of the drugs. Treatment of cultures with cytochalasin D, colchicine, or NOC for 1 hr before the addition of dibenz[a,c]anthracene had no effect of Cyp1a-1 induction, as monitored by measurements of CYP1A1 mRNA. Pretreatment with NOC for > or = 18 hr produced populations of cells that had either a flat or rounded morphology. Both populations, when isolated 20-24 hr after NOC treatment, were arrested in the G2/M phase of the cell cycle (83-98% in G2/M versus approximately 7-10% in nontreated or solvent-treated cultures). Cyp1a-1 induction was suppressed in both of these populations, as monitored by measurement of CYP1A1 mRNA content (reductions of > 68%), 7-ethoxyresorufin O-deethylase activity (reductions of > 80%), or microsomal CYP1A1 protein content (reductions of > 80%). In contrast, overall [3H]leucine incorporation into protein was not affected. Cytosol prepared from these NOC-treated cultures bound approximately 39% of the radiolabeled 2,3,7,8-tetrachlorodibenzo-p-dioxin bound by cytosol isolated from solvent-treated cultures. Nuclear extracts prepared from cultures treated with NOC for 20-24 hr before in vivo exposure to inducer and cytoplasmic extracts isolated from similarly NOC-treated cultures that were exposed to inducer in vitro demonstrated reductions of > or = 54% and > or = 55%, respectively, in their abilities to bind to DNA, when analyzed by gel retardation analyses using an oligonucleotide corresponding to dioxin-responsive element D of the Cyp1a-1 gene. These studies suggest that ligand-dependent induction of Cyp1a-1 transcription is unaffected by short term disruption of the microfilament or microtubule network. However, long term exposure to microtubule inhibitors causes cells to pause in the G2/M stage of the cell cycle and modulates processes involved in the induction of Cyp1a-1 in these cells.
journal_name
Mol Pharmacoljournal_title
Molecular pharmacologyauthors
Schöller A,Hong NJ,Bischer P,Reiners JJ Jrsubject
Has Abstractpub_date
1994-05-01 00:00:00pages
944-54issue
5eissn
0026-895Xissn
1521-0111journal_volume
45pub_type
杂志文章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::The phenylalkylamine emopamil prevents brain damage due to experimental cerebral ischemia. Stereoselective, high affinity, binding sites for (-)-[3H]emopamil in guinea pig brain cortex and liver membranes have been proposed to mediate its antiischemic effect. Using [N-methyl-3H]LU49888 as a photoaffinity probe we now ...
journal_title:Molecular pharmacology
pub_type: 杂志文章
doi:
更新日期:1993-02-01 00:00:00
abstract::The D2 dopamine receptor (D2R) was examined for its ability to mediate nuclear factor-kappaB (NF-kappaB) activation through G proteins. Stimulation of D2R-transfected HeLa cells with its agonist quinpirole induced the expression of a NF-kappaB luciferase reporter and formation of NF-kappaB-DNA complex. This response w...
journal_title:Molecular pharmacology
pub_type: 杂志文章
doi:10.1124/mol.64.2.447
更新日期:2003-08-01 00:00:00
abstract::15-Deoxy delta(12,14)-prostaglandin J(2) (15d-PGJ(2)), an activator of peroxisome proliferator-activated receptor (PPAR)-gamma and -delta, is a prostanoid metabolite with anti-inflammatory actions. In intrauterine tissues, proinflammatory cytokines and prostaglandins have been identified as playing key roles in the ma...
journal_title:Molecular pharmacology
pub_type: 杂志文章
doi:10.1124/mol.104.009449
更新日期:2005-07-01 00:00:00
abstract::Mutations that inhibit Kv11.1 ion channel activity contribute to abnormalities of cardiac repolarization that can lead to long QT2 (LQT2) cardiac arrhythmias and sudden death. However, for most of these mutations, nothing is known about the molecular mechanism linking Kv11.1 malfunction to cardiac death. We have previ...
journal_title:Molecular pharmacology
pub_type: 杂志文章
doi:10.1124/mol.112.077966
更新日期:2012-09-01 00:00:00
abstract::Glucose utilization in isolated islets of Langerhans of the rat was determined by measuring the conversion of [5-3H]glucose (10 mM) to 3H2O. The alpha 2-adrenoceptor agonists clonidine, epinephrine, and norepinephrine in the presence of the alpha 1-adrenoceptor antagonist prazosin and the beta-adrenoceptor antagonist ...
journal_title:Molecular pharmacology
pub_type: 杂志文章
doi:
更新日期:1987-08-01 00:00:00
abstract::Intermediate-conductance (KCa3.1) and small-conductance (KCa2) calcium-activated K+ channels are gated by calcium binding to calmodulin (CaM) molecules associated with the calmodulin-binding domain (CaM-BD) of these channels. The existing KCa activators, such as naphtho[1,2-d]thiazol-2-ylamine (SKA-31), 6,7-dichloro-1...
journal_title:Molecular pharmacology
pub_type: 杂志文章
doi:10.1124/mol.117.109421
更新日期:2017-10-01 00:00:00
abstract::Cytotoxic effects of quinones are thought to be mediated by redox cycles between quinones and quinols whereby reactive oxygen species are generated. The role of glucuronidation in preventing these toxic redox cycles was investigated by using benzo(a)pyrene-3,6-quinone and isolated rat hepatocytes or Reuber hepatoma ce...
journal_title:Molecular pharmacology
pub_type: 杂志文章
doi:
更新日期:1985-04-01 00:00:00
abstract::We have previously reported that endocytic sorting of ET(A) endothelin receptors to the recycling pathway is dependent on a signal residing in the cytoplasmic carboxyl-terminal region. The aim of the present work was to characterize the carboxyl-terminal recycling motif of the ET(A) receptor. Assay of truncation mutan...
journal_title:Molecular pharmacology
pub_type: 杂志文章
doi:10.1124/mol.104.007013
更新日期:2005-05-01 00:00:00
abstract::GABAA receptors are modulated by a variety of compounds, including the neurosteroids and barbiturates. Although the effects of barbiturates on alphabetagamma isoforms, thought to dominate phasic (synaptic) GABAergic inhibition, have been extensively studied, the effects of pentobarbital on kinetic properties of alphab...
journal_title:Molecular pharmacology
pub_type: 杂志文章
doi:10.1124/mol.104.002543
更新日期:2004-10-01 00:00:00
abstract::The microtubule-binding taxanes, docetaxel and cabazitaxel, are administered intravenously for the treatment of castration-resistant prostate cancer (CRPC) as the oral administration of these drugs is largely hampered by their low and highly variable bioavailabilities. Using a simple, rapid, and environmentally friend...
journal_title:Molecular pharmacology
pub_type: 杂志文章
doi:10.1124/mol.119.118539
更新日期:2020-06-01 00:00:00
abstract::Anaplastic thyroid carcinoma (ATC) is among the most aggressive malignancies known and is characterized with rapid growth, early invasion, and complete refractoriness to current therapies. Here we report that triptolide, a small molecule from a Chinese herb, could potently inhibit proliferation in vitro, angiogenesis ...
journal_title:Molecular pharmacology
pub_type: 杂志文章
doi:10.1124/mol.108.052605
更新日期:2009-04-01 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::The structure-activity relationships for vasoactive intestinal peptide (VIP) receptor binding were studied using N-terminally modified VIP analogs. VIP fragments, and VIP receptor antagonists. Tissue sources included bovine coronary artery, rat mesenteric artery, rat pituitary, rat brain synaptosomes, and rat liver. E...
journal_title:Molecular pharmacology
pub_type: 杂志文章
doi:
更新日期:1990-06-01 00:00:00
abstract::Multidrug and toxin extrusion 1 (MATE1/SLC47A1) is important for excretion of organic cations in the kidney and liver, where it is located on the luminal side. Although its functional and regulatory characteristics have been clarified, its pharmacokinetic roles in vivo have yet to be elucidated. In the present study, ...
journal_title:Molecular pharmacology
pub_type: 杂志文章
doi:10.1124/mol.109.056242
更新日期:2009-06-01 00:00:00
abstract::Agonist stimulation of group III metabotropic glutamate receptors (mGluRs) induces an inhibition of neurotransmitter release from neurons. The group III mGluRs are pharmacologically defined by activation with the glutamate analog L-amino-4-phosphonobutyric acid (L-AP4). The affinities of these receptors for L-AP4 and ...
journal_title:Molecular pharmacology
pub_type: 杂志文章
doi:10.1124/mol.104.002956
更新日期:2004-10-01 00:00:00
abstract::This study identifies signaling pathways activated by the beta(2)-/beta(3)-adrenoceptor (AR) agonist zinterol, the selective beta(3)-AR agonist L755507, and the selective beta(3)-AR antagonist L748337 in CHO-K1 cells expressing human beta(3)-adrenoceptors. Zinterol and L755507 caused a robust concentration-dependent i...
journal_title:Molecular pharmacology
pub_type: 杂志文章
doi:10.1124/mol.108.046979
更新日期:2008-11-01 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::Metabotropic glutamate receptor 5 (mGlu5) is a target for the treatment of central nervous system (CNS) disorders, such as schizophrenia and Alzheimer's disease. Furthermore, mGlu5 has been shown to play an important role in hippocampal synaptic plasticity, specifically in long-term depression (LTD) and long-term pote...
journal_title:Molecular pharmacology
pub_type: 杂志文章
doi:10.1124/mol.112.082891
更新日期:2013-04-01 00:00:00
abstract::It is established that agmatine, an endogenously formed decarboxylated arginine, is a weak competitive inhibitor of neuronal nitric-oxide synthase (nNOS) with an apparent Ki value of 660 microM [Biochem J 316:247-249, 1996]. Although agmatine is known to bind to alpha-adrenergic and imidazoline receptors, it has been ...
journal_title:Molecular pharmacology
pub_type: 杂志文章
doi:10.1124/mol.59.1.24
更新日期:2001-01-01 00:00:00
abstract::The effect of lysosomotropic agents and secretory inhibitors were compared with verapamil for their effect on the activity of doxorubicin (DOX) in multiple drug-resistant (MDR) P388 leukemia cells (P388R) and in blocking anthracycline efflux from these cells. Agents known to interact with the plasma membrane did not p...
journal_title:Molecular pharmacology
pub_type: 杂志文章
doi:
更新日期:1988-08-01 00:00:00
abstract::The role of mitogen-activated protein kinase signaling and the transcription factor c-Jun in epidermal growth factor (EGF)-induced expression of 12-lipoxygenase in human epidermoid carcinoma A431 cells was studied. EGF increased the activation of extracellular signal-regulated kinase (ERK) and c-Jun amino terminal kin...
journal_title:Molecular pharmacology
pub_type: 杂志文章
doi:
更新日期:2000-01-01 00:00:00
abstract::We showed previously that subtypes of alpha 1-adrenergic receptors can be differentiated by selective inactivation with chlorethylclonidine (CEC) [Mol. Pharmacol. 32:505-510 (1987)] or by their affinities for the competitive antagonist WB 4101 [Nature (Lond.) 329:333-335 (1987)]. Examining eight rat tissues, the propo...
journal_title:Molecular pharmacology
pub_type: 杂志文章
doi:
更新日期:1988-05-01 00:00:00
abstract::The purpose of these studies was to support the hypothesis that an undiscovered cannabinoid receptor exists in brain. [(35)S]GTP gamma S binding was stimulated by anandamide and WIN55212-2 in brain membranes from both CB(1)(+/+) and CB(1)(-/-) mice. In contrast, a wide variety of other compounds that are known to acti...
journal_title:Molecular pharmacology
pub_type: 杂志文章
doi:
更新日期:2001-07-01 00:00:00
abstract::Tienilic acid-induced hepatitis is characterized by the presence of anti-liver and -kidney microsomal (anti-LKM2) autoantibodies in patient sera. Cytochrome P4502C9(CYP2C9), involved in the metabolism of tienilic acid, was shown to be a target for tienilic acid-reactive metabolites and for autoantibodies. To further i...
journal_title:Molecular pharmacology
pub_type: 杂志文章
doi:
更新日期:1996-08-01 00:00:00
abstract::Receptors have well-conserved regions that are recognized and activated by hormones and neurotransmitters. Most drugs bind to these sites and mimic or block the action of the native ligands. Using a high-throughput functional screen, we identified a potent and selective M(1) muscarinic receptor agonist from a novel st...
journal_title:Molecular pharmacology
pub_type: 杂志文章
doi:10.1124/mol.61.6.1297
更新日期:2002-06-01 00:00:00
abstract::Three different cDNA clones, namely DM1-1, Dah1, and Dah2, encoding hepatic cytochrome P-450, were isolated from a cDNA library in lambda gt11 constructed from liver RNA of polychlorinated biphenyl-treated beagle dogs. DM1-1 was 1857 base pairs (bp) long and encoded a polypeptide of 457 residues. Dah1 was 2394 bp long...
journal_title:Molecular pharmacology
pub_type: 杂志文章
doi:
更新日期:1990-11-01 00:00:00
abstract::Aldehyde dehydrogenase-2 (ALDH2) catalyzes vascular bioactivation of the antianginal drug nitroglycerin (GTN) to yield nitric oxide (NO) or a related species that activates soluble guanylate cyclase (sGC), resulting in cGMP-mediated vasodilation. Accordingly, established ALDH2 inhibitors attenuate GTN-induced vasorela...
journal_title:Molecular pharmacology
pub_type: 杂志文章
doi:10.1124/mol.113.086835
更新日期:2013-09-01 00:00:00
abstract::The present study investigates mRNA and protein levels of A3 adenosine receptors in resting (R) and activated (A) human lymphocytes. The receptors were evaluated by the antagonist radioligand [3H]5-N-(4-methoxyphenyl-carbamoyl)amino-8-propyl-2(2furyl)-pyrazolo-[4,3e]-1,2,4-triazolo-[1,5-c]-pyrimidine ([3H]MRE 3008F20)...
journal_title:Molecular pharmacology
pub_type: 杂志文章
doi:10.1124/mol.65.3.711
更新日期:2004-03-01 00:00:00
abstract::The role of the cGMP-dependent protein kinase (cGK) and one of its major substrates, the vasodilator-stimulated phosphoprotein (VASP), in the regulation of a receptor-evoked calcium response was investigated. The human type I beta cGK was stably transfected in human embryonic kidney 293 cells and Swiss mouse 3T6 fibro...
journal_title:Molecular pharmacology
pub_type: 杂志文章
doi:
更新日期:1994-08-01 00:00:00