Abstract：
:Iron is a biologically essential metal, but excess iron can cause damage to the cardiovascular and nervous systems. We examined the effects of extracellular Fe²⁺ on permeation and gating of Ca(V)3.1 channels stably transfected in HEK293 cells, by using whole-cell recording. Precautions were taken to maintain iron in the Fe²⁺ state (e.g., use of extracellular ascorbate). With the use of instantaneous I-V currents (measured after strong depolarization) to isolate the effects on permeation, extracellular Fe²⁺ rapidly blocked currents with 2 mM extracellular Ca²⁺ in a voltage-dependent manner, as described by a Woodhull model with K(D) = 2.5 mM at 0 mV and apparent electrical distance δ = 0.17. Extracellular Fe²⁺ also shifted activation to more-depolarized voltages (by ∼10 mV with 1.8 mM extracellular Fe²⁺) somewhat more strongly than did extracellular Ca²⁺ or Mg²⁺, which is consistent with a Gouy-Chapman-Stern model with surface charge density σ = 1 e(-)/98 Ų and K(Fe) = 4.5 M⁻¹ for extracellular Fe²⁺. In the absence of extracellular Ca²⁺ (and with extracellular Na⁺ replaced by TEA), Fe²⁺ carried detectable, whole-cell, inward currents at millimolar concentrations (73 ± 7 pA at -60 mV with 10 mM extracellular Fe²⁺). With a two-site/three-barrier Eyring model for permeation of Ca(V)3.1 channels, we estimated a transport rate for Fe²⁺ of ∼20 ions/s for each open channel at -60 mV and pH 7.2, with 1 μM extracellular Fe²⁺ (with 2 mM extracellular Ca²⁺). Because Ca(V)3.1 channels exhibit a significant "window current" at that voltage (open probability, ∼1%), Ca(V)3.1 channels represent a likely pathway for Fe²⁺ entry into cells with clinically relevant concentrations of extracellular Fe²⁺.
journal_name
Mol Pharmacoljournal_title
Molecular pharmacologyauthors
Lopin KV,Gray IP,Obejero-Paz CA,Thévenod F,Jones SWdoi
10.1124/mol.112.080184subject
Has Abstractpub_date
2012-12-01 00:00:00pages
1194-204issue
6eissn
0026-895Xissn
1521-0111pii
mol.112.080184journal_volume
82pub_type
杂志文章abstract：:The ability of four antidepressant drugs, imipramine, alaproclate, norzimelidine, and fluvoxamine, to inhibit serotonin transport into platelet plasma membrane vesicles was tested over a range of external Na+ concentrations. Imipramine affinity, as we previously reported [J. Biol. Chem. 258:6115-6119 (1983)] increases...
journal_title：Molecular pharmacology
pub_type： 杂志文章
doi：
更新日期：1988-06-01 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：:A recently developed stable isotope dilution liquid chromatography-multiple reaction/mass spectrometry method to quantify focal adhesion kinase (FAK) activation loop phosphorylation was used to study endogenous Src kinase activity. This revealed that bis-phosphorylated pTyr(576)/Tyr(577)-FAK was a biomarker of Src act...
journal_title：Molecular pharmacology
pub_type： 杂志文章
doi：10.1124/mol.108.052464
更新日期：2009-03-01 00:00:00
abstract：:The interaction between some examples of mononuclear and binuclear DNA-intercalating antitumor agents and alpha- and beta-adrenoceptors has been studied using radioligand-binding assays. Competition for 125I-BE 2254, [3H]rauwolscine, and (-)-[3H]dihydroalprenolol binding was used to assess affinity for alpha 1-, alpha...
journal_title：Molecular pharmacology
pub_type： 杂志文章
doi：
更新日期：1985-04-01 00:00:00
abstract：:The dissociation constants (Kd values) of substance P (SP), physalaemin, kassinin, and SP analogues acting on SP receptors in guinea pig ileal longitudinal muscle strips were determined by the pharmacological procedures of Furchgott [Adv. Drug Res. 3:21-55 (1966)]. This method involves analysis of the concentration-re...
journal_title：Molecular pharmacology
pub_type： 杂志文章
doi：
更新日期：1983-05-01 00:00:00
abstract：:Previously we demonstrated that aldehyde dehydrogenase (ALDH) 1a1 is the major ALDH expressed in mouse liver and is an effective catalyst in metabolism of lipid aldehydes. Quantitative real-time polymerase chain reaction analysis revealed a ≈2.5- to 3-fold induction of the hepatic ALDH1A1 mRNA in mice administered eit...
journal_title：Molecular pharmacology
pub_type： 杂志文章
doi：10.1124/mol.112.078147
更新日期：2012-10-01 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：:The binding of two anthranilic acid derivatives, glafenic and floctafenic acids, to human erythrocytes and plasma proteins has been investigated in vitro by equilibrium dialysis. Despite their close chemical structures it was shown that the binding of the two compounds to serum albumin, lipoproteins, and erythrocytes ...
journal_title：Molecular pharmacology
pub_type： 杂志文章
doi：
更新日期：1987-03-01 00:00:00
abstract：:The successful synthesis of dolastatin 11, a depsipeptide originally isolated from the mollusk Dolabella auricularia, permitted us to study its effects on cells. The compound arrested cells at cytokinesis by causing a rapid and massive rearrangement of the cellular actin filament network. In a dose-and time-dependent ...
journal_title：Molecular pharmacology
pub_type： 杂志文章
doi：10.1124/mol.59.3.462
更新日期：2001-03-01 00:00:00
abstract：:Glioma cells with stem cell properties, termed glioma stem-like cells (GSCs), have been linked to tumor formation, maintenance, and progression and are responsible for the failure of chemotherapy and radiotherapy. Because conventional glioma treatments often fail to eliminate GSCs completely, residual surviving GSCs a...
journal_title：Molecular pharmacology
pub_type： 杂志文章
doi：10.1124/mol.112.078402
更新日期：2012-09-01 00:00:00
abstract：:Melanocortins (MCs) have various physiological actions on the brain. The recent cloning of neural MC receptors opened new avenues to study the effects of these neuropeptides on the nervous system. Here we investigated the structure-activity relationships (SARs) of peptides derived from adrenocorticotropic hormone (ACT...
journal_title：Molecular pharmacology
pub_type： 杂志文章
doi：
更新日期：1994-12-01 00:00:00
abstract：:Cytochrome P450 (P450) enzymes are responsible for metabolizing drugs. Expression of P450s can directly affect drug metabolism, resulting in various outcomes in therapeutic efficacy and adverse effects. Several nuclear receptors are transcription factors that can regulate expression of P450s at both basal and drug-ind...
journal_title：Molecular pharmacology
pub_type： 杂志文章
doi：10.1124/mol.118.112235
更新日期：2018-07-01 00:00:00
abstract：:N-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) induces Parkinson-like symptoms in humans, nonhuman primates, and mice. Several studies suggest that MPTP is metabolized by monoamine oxidase (MAO) type B to yield N-methyl-4-phenyl-pyridinium (MPP+), which is responsible for the neurotoxic effects of the drug. In th...
journal_title：Molecular pharmacology
pub_type： 杂志文章
doi：
更新日期：1991-03-01 00:00:00
abstract：:Identifying novel mechanisms to enhance glucagon-like peptide-1 (GLP-1) receptor signaling may enable nascent medicinal chemistry strategies with the aim of developing new orally available therapeutic agents for the treatment of type 2 diabetes mellitus. Therefore, we tested the hypothesis that selectively modulating ...
journal_title：Molecular pharmacology
pub_type： 杂志文章
doi：10.1124/mol.112.080432
更新日期：2012-12-01 00:00:00
abstract：:Noscapine, a microtubule-interfering agent, has been shown to arrest mitosis, to induce apoptosis, and to have potent antitumor activity. We report herein that two brominated derivatives of noscapine, 5-bromonoscapine (5-Br-nosc) and reduced 5-bromonoscapine (Rd 5-Br-nosc), have higher tubulin binding activity than no...
journal_title：Molecular pharmacology
pub_type： 杂志文章
doi：10.1124/mol.63.4.799
更新日期：2003-04-01 00:00:00
abstract：:A fusion protein consisting of the endothelin B (ET(B)) receptor and the enhanced green fluorescent protein (EGFP) in conjunction with Cyanin3- or fluorescein-conjugated endothelin 1 (Cy3-ET1, Fluo-ET1) was used to investigate the ligand-mediated internalization of the ET(B) receptor. The ET(B) receptor and the ET(B)/...
journal_title：Molecular pharmacology
pub_type： 杂志文章
doi：
更新日期：2000-06-01 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：:Wild-type p53 is frequently mutated in late-stage ovarian cancer and has been proposed as a determinant of cisplatin chemosensitivity. We have therefore established a human ovarian cancer cell line differing only in p53 status and characterized its response after treatment with different platinum complexes. The wild-t...
journal_title：Molecular pharmacology
pub_type： 杂志文章
doi：10.1124/mol.57.3.503
更新日期：2000-03-01 00:00:00
abstract：:We investigated the mechanisms of MDR1 gene activation by CCAAT/enhancer binding protein beta (C/EBPbeta, or nuclear factor for interleukin 6) in human cancer cells. Transfection of the breast cancer cell line MCF-7 and its doxorubicin-selected variant MCF-7/ADR by either C/EBPbeta or C/EBPbeta-LIP (a dominant-negativ...
journal_title：Molecular pharmacology
pub_type： 杂志文章
doi：10.1124/mol.65.4.906
更新日期：2004-04-01 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：: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：:The phosphorylation of μ-opioid receptors (MOPRs) by G protein-coupled receptor kinases (GRKs), followed by arrestin binding, is thought to be a key pathway leading to desensitization and internalization. The present study used the combination of intracellular and whole-cell recordings from rats and mice, as well as l...
journal_title：Molecular pharmacology
pub_type： 杂志文章
doi：10.1124/mol.111.076208
更新日期：2012-03-01 00:00:00
abstract：:The relations between the single high affinity binding sites for azapropazone, phenylbutazone, chlorpropamide, sulfathiazole, and iophenoxate and the binding regions of human serum albumin represented by the marker ligands diazepam, phenol red, salicylate, and warfarin were examined by a series of competition experime...
journal_title：Molecular pharmacology
pub_type： 杂志文章
doi：
更新日期：1988-08-01 00:00:00
abstract：:4-Methyl-5-(2-pyrazinyl)-1,2-dithiole-3-thione (oltipraz), a prototype drug candidate containing a 1,2-dithiole-3-thione moiety, has been widely studied as a cancer chemopreventive agent. Oltipraz and other novel 1,2-dithiole-3-thione congeners have the capability to prevent insulin resistance via AMP-activated protei...
journal_title：Molecular pharmacology
pub_type： 杂志文章
doi：10.1124/mol.108.051128
更新日期：2009-01-01 00:00:00
abstract：:The members of the Cys-loop ligand-gated ion channel (LGIC) gene family play a major role in fast synaptic transmission, and these receptors represent an important class of targets for therapeutic agents. Each member of this gene family is a pentameric complex containing one or more different subunits, and a large num...
journal_title：Molecular pharmacology
pub_type： 评论,杂志文章,评审
doi：10.1124/mol.105.020727
更新日期：2006-02-01 00:00:00
abstract：:Opioid analgesics are used extensively in the management of pain. Although the clinically effective opioids bind with high affinity to the mu-opioid receptor, studies have suggested that the delta-opioid agonists might represent more ideal analgesic agents, with fewer side effects. A limitation to opiate effectiveness...
journal_title：Molecular pharmacology
pub_type： 杂志文章
doi：10.1124/mol.52.2.272
更新日期：1997-08-01 00:00:00
abstract：:Activation of synthesis-modulating dopamine autoreceptors by dopamine or its agonists has been shown to inhibit dopamine synthesis in the rat striatum. However, systemic administration of the direct-acting dopamine agonist apomorphine failed to inhibit dopamine synthesis in striata from rats that had received local un...
journal_title：Molecular pharmacology
pub_type： 杂志文章
doi：
更新日期：1988-12-01 00:00:00
abstract：:Two forms of the multisubunit gamma-aminobutyric acid (GABA)A receptor were expressed in Xenopus oocytes by injecting mRNA encoding the bovine GABAA receptor subunit cDNAs for alpha 1 beta 1 gamma 2L and alpha 3 beta 1 gamma 2L. The properties of these two combinations were examined by electrophysiological recording o...
journal_title：Molecular pharmacology
pub_type： 杂志文章
doi：
更新日期：1993-02-01 00:00:00
abstract：:Platelet-derived growth factor (PDGF) and PDGF receptors (PDGFRs) are ubiquitously expressed in the mammalian central nervous system, where they exert trophic actions on both neuronal and glial cells. However, the acute actions of PDGF on synaptic transmission are unknown. We report a novel regulatory action of PDGF/P...
journal_title：Molecular pharmacology
pub_type： 杂志文章
doi：
更新日期：1995-12-01 00:00:00
abstract：:The effects of the non-tumor-promoting protein kinase C (PKC) activator bryostatin 1 and the PKC inhibitors staurosporine and UCN-01 were examined with respect to modulation of 1-[beta-D-arabinofuranosyl]cytosine (ara-C)-induced apoptosis in human myeloid leukemia cells (HL-60) overexpressing the antiapoptotic protein...
journal_title：Molecular pharmacology
pub_type： 杂志文章
doi：10.1124/mol.52.6.1000
更新日期：1997-12-01 00:00:00
