Abstract：
:Based on the available data, we speculated that changes in brain iron metabolism induced by L-DOPA might be associated with the neurotoxicity of L-DOPA. To investigate this possibility, the effects of L-DOPA on the expression of iron influx proteins [transferrin receptor (TfR) and divalent metal transporter 1 (DMT1)], iron efflux protein (ferroportin 1), and iron uptake in C6 glioma cells were determined in this study using Northern blot and Western blot analysis and the calcein method. The findings showed that treatment of C6 cells with different concentrations of L-DOPA (0-100 microM) did not affect the expression of mRNA and protein of TfR and DMT1 with iron-responsive element (+IRE) and protein of ferroportin 1. However, a significant increase in the expression of DMT1(-IRE) mRNA and protein was found in cells treated, respectively, with 10 and 30 microM L-DOPA (mRNA) and 1, 5, 10 and 30 microM L-DOPA (protein). The increase in DMT(-IRE) protein induced by L-DOPA treatment was in parallel with the increase in DMT(-IRE) mRNA. The levels of DMT1(-IRE) mRNA and protein peaked in the cells treated with 10 microM L-DOPA and then decreased progressively with increasing concentrations of L-DOPA. Further study demonstrated that treatment of the cells with 10 microM L-DOPA induced a significant increase in ferrous uptake by C6 glioma cells. The findings suggested that the increased DMT1(-IRE) expression might be partly associated with the neurotoxicity of L-DOPA. Clinical relevance of the findings needs to be investigated further.
journal_name
Mol Pharmacoljournal_title
Molecular pharmacologyauthors
Chang YZ,Ke Y,Du JR,Halpern GM,Ho KP,Zhu L,Gu XS,Xu YJ,Wang Q,Li LZ,Wang CY,Qian ZMdoi
10.1124/mol.105.017756keywords:
subject
Has Abstractpub_date
2006-03-01 00:00:00pages
968-74issue
3eissn
0026-895Xissn
1521-0111pii
mol.105.017756journal_volume
69pub_type
杂志文章abstract：:Heart cells in culture need no external stimulation to contract; they beat rhythmically at a rate and intensity dependent on culture conditions. These cells respond to the general anesthetic 2-bromo-2-chloro-1,1,1-trifluorethane (halothane), with a loss of beating intensity and a lessening of beating rate. Increased c...
journal_title：Molecular pharmacology
pub_type： 杂志文章
doi：
更新日期：1983-03-01 00:00:00
abstract：:The insecticide imidacloprid and structurally related neonicotinoids act selectively on insect nicotinic acetylcholine receptors (nAChRs). To investigate the mechanism of neonicotinoid selectivity, we have examined the effects of mutations to basic amino acid residues in loop D of the nAChR acetylcholine (ACh) binding...
journal_title：Molecular pharmacology
pub_type： 杂志文章
doi：10.1124/mol.106.026815
更新日期：2006-10-01 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：:In an attempt to better understand the role of the cyclohexene ring (ring A) in the biochemical and pharmacological properties of anthracyclines related to doxorubicin and daunorubicin, we investigated the effects of introduction of a fluorine atom at position 8 of idarubicin (4-demethoxydaunorubicin) on drug molecula...
journal_title：Molecular pharmacology
pub_type： 杂志文章
doi：
更新日期：1996-09-01 00:00:00
abstract：:Increasing data indicate that brain endocannabinoid system plays a role in the effects of antidepressant medications. Here we examined the effect of in vivo exposure to the selective serotonin uptake inhibitor fluoxetine on cannabinoid type 1 (CB(1)) receptor density and functionality in the rat prefrontal cortex (PFC...
journal_title：Molecular pharmacology
pub_type： 杂志文章
doi：10.1124/mol.109.060079
更新日期：2010-03-01 00:00:00
abstract：:Comparative molecular field analysis (CoMFA) predicts that the large electrostatic field around the phosphate groups of ATP plays a crucial role in stabilizing the open state of the cardiac ryanodine receptor (RyR) channel. We therefore investigated the effects of adenosine-5'-(beta,gamma-methylenetriphosphate) (AMP-P...
journal_title：Molecular pharmacology
pub_type： 杂志文章
doi：10.1124/mol.63.1.174
更新日期：2003-01-01 00:00:00
abstract：:The effects of the insulin-releasing sulfonylurea tolbutamide on the cytoplasmic Ca2+ concentration [( Ca2+]i) in individual pancreatic beta-cells or suspensions of beta-cells were analyzed using the probe fura-2 and dual-wavelength fluorometry. Subsequent additions of 1, 10, and 100 microM tolbutamide induced a grade...
journal_title：Molecular pharmacology
pub_type： 杂志文章
doi：
更新日期：1990-03-01 00:00:00
abstract：:Tritiated dextromethorphan ([3H]DM) binds to two distinct sites in guinea pig brain, a high-affinity site (Kd = 13-20 nM) and a low-affinity site (Kd greater than 200 nM). Binding of [3H] DM to the high-affinity site is rapid, reversible, saturable, proportional to tissue concentration, and pH-dependent. The sites hav...
journal_title：Molecular pharmacology
pub_type： 杂志文章
doi：
更新日期：1983-05-01 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：:Aspartyl aminopeptidase (DNPEP) has been implicated in the control of angiotensin signaling and endosome trafficking, but its precise biologic roles remain incompletely defined. We performed a high-throughput screen of ∼25,000 small molecules to identify inhibitors of DNPEP for use as tools to study its biologic funct...
journal_title：Molecular pharmacology
pub_type： 杂志文章
doi：10.1124/mol.114.093070
更新日期：2014-08-01 00:00:00
abstract：:Previous studies have established that two Xbal polymorphic restriction fragments [11.5 and 44 kilobases (kb)] hydridizing to a full length debrisoquin hydroxylase cDNA are associated with two different mutant alleles for the debrisoquin hydroxylase gene (IID6). An independent allele, defined by Xbal 16- and 9-kb frag...
journal_title：Molecular pharmacology
pub_type： 杂志文章
doi：
更新日期：1990-05-01 00:00:00
abstract：:A method was developed to measure the formation of glutathione adducts of 1-chloro-2,4-dinitrobenzene (CDNB) and 2,4-dichloro-1-nitrobenzene (DCNB) in periportal and pericentral regions of the liver lobule in the isolated perfused rat liver by surface reflectance spectrophotometry. Conjugates of DCNB and CDNB are rele...
journal_title：Molecular pharmacology
pub_type： 杂志文章
doi：
更新日期：1986-01-01 00:00:00
abstract：:The heptadecapeptide orphanin FQ (OFQ) has been identified as the endogenous ligand for a G protein-coupled receptor (OFQ-R), which, despite its high degree of sequence similarity to opioid receptors, fails to bind opioid ligands. We developed two radioligands for the OFQ-R: a tritiated native OFQ peptide ([3H]OFQ) an...
journal_title：Molecular pharmacology
pub_type： 杂志文章
doi：10.1124/mol.51.5.816
更新日期：1997-05-01 00:00:00
abstract：:Aflatrem, a mycotoxin from Aspergillus flavus, potentiates the gamma-aminobutyric acid (GABA)-induced chloride current. This positive allosteric regulatory action of aflatrem was quantitatively studied on the GABAA receptor channel expressed in Xenopus oocytes after injection with chick brain mRNA under voltage-clamp ...
journal_title：Molecular pharmacology
pub_type： 杂志文章
doi：
更新日期：1989-03-01 00:00:00
abstract：:15-Deoxy-Delta(12,14)-prostaglandin J(2) (15d-PGJ(2)) is a cyclopentenonic prostaglandin endowed with powerful anti-inflammatory activities, as shown in animal models of inflammatory/autoimmune diseases, where pharmacological administration of this prostanoid can ameliorate inflammation and local tissue damage via act...
journal_title：Molecular pharmacology
pub_type： 杂志文章
doi：10.1124/mol.107.038042
更新日期：2007-11-01 00:00:00
abstract：:Binding by 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) to the Ah receptor leads to transcriptional activation of several genes and a toxicity syndrome that includes tumor promotion, wasting, hormonal and immune system dysfunction, and death. Recent findings indicate that TCDD may also affect cardiac function. Here, we ...
journal_title：Molecular pharmacology
pub_type： 杂志文章
doi：
更新日期：1993-12-01 00:00:00
abstract：:The nuclear receptor peroxisome proliferator-activated receptor (PPAR) is activated by a diverse group of acidic ligands, including many peroxisome proliferator chemicals present in the environment. Janus tyrosine kinase-signal transducer and activator of transcription (JAK-STAT) signaling is activated by multiple cyt...
journal_title：Molecular pharmacology
pub_type： 杂志文章
doi：10.1124/mol.64.2.355
更新日期：2003-08-01 00:00:00
abstract：:Excitotoxin-induced destruction of striatal neurons, proposed as a model of Huntington's disease, involves a process having the biochemical stigmata of apoptosis. Recent studies suggested that transcription factor nuclear factor (NF)-kappa B may be involved in excitotoxicity. To further analyze the contribution of NF ...
journal_title：Molecular pharmacology
pub_type： 杂志文章
doi：10.1124/mol.53.1.33
更新日期：1998-01-01 00:00:00
abstract：:The orphan nuclear receptor liver receptor homolog 1 (LRH-1; NR5A2) is a potent regulator of cholesterol metabolism and bile acid homeostasis. Recently, LRH-1 has been shown to play an important role in intestinal inflammation and in the progression of estrogen receptor positive and negative breast cancers and pancrea...
journal_title：Molecular pharmacology
pub_type： 杂志文章
doi：10.1124/mol.114.095554
更新日期：2015-02-01 00:00:00
abstract：:An investigation of the conformational profiles of two cyclic delta-selective opioid peptides, [D-Pen2,D-Pen5]-enkephalin and [D-Pen2,L-Pen5]-enkephalin, has been made. The methods and procedures used are more extensive and systematic than those previously reported, involving a combination of nested grid rotations, cy...
journal_title：Molecular pharmacology
pub_type： 杂志文章
doi：
更新日期：1991-04-01 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：:Inhibition of cathepsin C, a dipeptidyl peptidase that activates many serine proteases, represents an attractive therapeutic strategy for inflammatory diseases with a high neutrophil burden. We recently showed the feasibility of blocking the activation of neutrophil elastase, cathepsin G, and proteinase-3 with a singl...
journal_title：Molecular pharmacology
pub_type： 杂志文章
doi：10.1124/mol.108.045682
更新日期：2008-06-01 00:00:00
abstract：:DNA topoisomerases are the molecular targets of a range of anticancer and antimicrobial therapeutics. Many of these drugs act by converting their target enzyme to a DNA-damaging agent through the trapping of the covalent enzyme/DNA intermediate. This drug-mediated trapping of the intermediate is reversible, and the le...
journal_title：Molecular pharmacology
pub_type： 杂志文章
doi：
更新日期：1996-11-01 00:00:00
abstract：:Bufuralol 1'-hydroxylation is a prototypical reaction catalyzed by cytochrome P450 (P450) 2D6, an enzyme known to show debrisoquine/sparteine-type genetic polymorphism in humans. In the present study we further examined the roles of several human P450 enzymes, as well as P450 2D6, in the hydroxylation of (+/-)-bufural...
journal_title：Molecular pharmacology
pub_type： 杂志文章
doi：
更新日期：1994-09-01 00:00:00
abstract：:Smooth muscle preparations of human aorta or pig coronary arteries contain nearly equal amounts of cGMP-dependent protein kinase isozymes (cGMP kinase I alpha and I beta). In order to understand the roles of these isozymes in relaxing vascular smooth muscle, several new cGMP analogs were synthesized and tested for pot...
journal_title：Molecular pharmacology
pub_type： 杂志文章
doi：
更新日期：1992-07-01 00:00:00
abstract：:In ND8-47 cells, a neuroblastoma x dorsal root ganglion hybrid cell line, activation of delta-opioid receptors induced an increase in the intracellular free calcium concentration ([Ca2+]i) through dihydropyridine-sensitive calcium channels. This effect was mediated by pertussis toxin-sensitive G proteins. The G protei...
journal_title：Molecular pharmacology
pub_type： 杂志文章
doi：
更新日期：1995-08-01 00:00:00
abstract：:Mouse embryonic spinal cord neurons in culture exhibit spontaneous calcium oscillations from day in vitro (DIV) 6 through DIV 10. Such spontaneous activity in developing spinal cord contributes to maturation of synapses and development of pattern-generating circuits. Here we demonstrate that these calcium oscillations...
journal_title：Molecular pharmacology
pub_type： 杂志文章
doi：10.1124/mol.111.071456
更新日期：2011-06-01 00:00:00
abstract：:We have identified alpha 2-adrenergic receptors on human erythroleukemia (HEL) cells, a suspension-grown cell line related to human platelets. properties of receptors were assessed in intact cells by binding of the antagonist [3H]yohimbine and by inhibition of cAMP accumulation. [3H]Yohimbine labeled 5900 +/- 2100 rec...
journal_title：Molecular pharmacology
pub_type： 杂志文章
doi：
更新日期：1987-08-01 00:00:00
abstract：:Hypertriglyceridemia is a frequent complication accompanying the treatment of patients with either retinoids or rexinoids, [retinoid X receptor (RXR)-selective retinoids]. To investigate the cellular and molecular basis for this observation, we have studied the effects of rexinoids on triglyceride metabolism in both n...
journal_title：Molecular pharmacology
pub_type： 杂志文章
doi：10.1124/mol.59.2.170
更新日期：2001-02-01 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
