Abstract：
:The mammalian copper transporter 1 (CTR1) is responsible for the uptake of copper from the extracellular space. In this study, we used an isogenic pair of CTR1(+/+) and CTR1(-/-) mouse embryo fibroblasts to examine the contribution of CTR1 to the influx of cisplatin (DDP), carboplatin (CBDCA), oxaliplatin (L-OHP), and transplatin. Exposure to DDP triggered the rapid degradation of CTR1, suggesting that its contribution to influx was likely to be on the initial phase of drug entry. Loss of CTR1 decreased the initial binding of DDP to cells and reduced influx measured over the first 5 min of drug exposure by 81%. Loss of CTR1 almost completely eliminated the initial influx of CBDCA and reduced the initial uptake of L-OHP by 68% but had no effect on the influx of transplatin. Loss of CTR1 rendered cells resistant to even high concentrations of DDP when measured in vitro, and re-expression of CTR1 in the CTR1(-/-) cells restored both DDP uptake and cytotoxicity. The growth of CTR1(-/-) tumor xenografts in which CTR1 levels were restored by infection with a lentivirus expressing wild-type CTR1 was reduced by a single maximum tolerated dose of DDP in vivo, whereas the CTR1(-/-) xenografts failed to respond at all. We conclude that CTR1 mediates the initial influx of DDP, CBDCA, and L-OHP and is a major determinant of responsiveness to DDP both in vitro and in vivo.
journal_name
Mol Pharmacoljournal_title
Molecular pharmacologyauthors
Larson CA,Blair BG,Safaei R,Howell SBdoi
10.1124/mol.108.052381subject
Has Abstractpub_date
2009-02-01 00:00:00pages
324-30issue
2eissn
0026-895Xissn
1521-0111pii
mol.108.052381journal_volume
75pub_type
杂志文章abstract：:The growth of Plasmodium falciparum, a human malaria parasite, is sensitive to inhibition by chelators of several types. The alkylthiocarbamates and 8-hydroxyquinoline at pharmacologic doses selectively inhibit glycolysis within 6 hr in parasitized erythrocytes. The mechanism attributed to these agents is through the ...
journal_title：Molecular pharmacology
pub_type： 杂志文章
doi：
更新日期：1986-10-01 00:00:00
abstract：:Monoamine oxidases (MAOs) A and B, flavin-containing enzymes found in the outer mitochondrial membrane, oxidize many important biogenic and xenobiotic amines. The two enzymes are expressed in many tissues, with some tissues containing primarily one form and others containing both. Although MAO in placental mitochondri...
journal_title：Molecular pharmacology
pub_type： 杂志文章
doi：
更新日期：1989-07-01 00:00:00
abstract：:The aryl hydrocarbon receptor (AHR) is a ligand-activated transcription factor with constitutive activities and those induced by xenobiotic ligands, such as 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD). One unexplained cellular role for the AHR is its ability to promote cell cycle progression in the absence of exogenous...
journal_title：Molecular pharmacology
pub_type： 杂志文章
doi：10.1124/mol.109.059675
更新日期：2010-02-01 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：:A methylcholanthrene-induced rat sarcoma that can be propagated in vitro or in vivo was evaluated for resistance to antifolates and was found to be relatively resistant to methotrexate and 10-ethyl-10-deazaaminopterin but sensitive to trimetrexate. Rat sarcoma cell extracts contained low levels of dihydrofolate reduct...
journal_title：Molecular pharmacology
pub_type： 杂志文章
doi：
更新日期：1991-11-01 00:00:00
abstract：:5-Hydroxytryptamine3 (5-HT3) receptors are ligand-gated ion channels that mediate neurotransmission by serotonin in the central nervous system. Pharmacological inhibition of 5-HT3 receptor activity has therapeutic potential in several psychiatric diseases, including depression and anxiety. The recently approved multim...
journal_title：Molecular pharmacology
pub_type： 杂志文章
doi：10.1124/mol.118.113530
更新日期：2018-12-01 00:00:00
abstract：:The compound 4-(5-(4-bromophenyl)-3-(6-methyl-2-oxo-4-phenyl-1,2-dihydroquinolin-3-yl)-4,5-dihydro-1H-pyrazol-1-yl)-4-oxobutanoic acid (DQP-1105) is a representative member of a new class of N-methyl-d-aspartate (NMDA) receptor antagonists. DQP-1105 inhibited GluN2C- and GluN2D-containing receptors with IC(50) values ...
journal_title：Molecular pharmacology
pub_type： 杂志文章
doi：10.1124/mol.111.073239
更新日期：2011-11-01 00:00:00
abstract：:Taxanes act by inhibiting microtubule dynamics; in this study, we have investigated mitochondria as an additional target of taxanes. We incubated isolated mitochondria in the presence of taxanes with or without stimulation of the mitochondrial respiratory state. Results showed that they rapidly induced the loss of del...
journal_title：Molecular pharmacology
pub_type： 杂志文章
doi：10.1124/mol.64.1.51
更新日期：2003-07-01 00:00:00
abstract：:The cytolytic ionotropic ATP receptor P2X7 has several important roles in immune cell regulation, such as cytokine release, apoptosis, and microbial killing. Although P2X7 receptors are frequently coexpressed with another subtype of P2X receptor, P2X4, they are believed not to form heteromeric assemblies but to functi...
journal_title：Molecular pharmacology
pub_type： 杂志文章
doi：10.1124/mol.107.035980
更新日期：2007-12-01 00:00:00
abstract：:Voltage-gated potassium (Kv) channels regulate many physiological functions and represent important therapeutic targets in the treatment of several clinical disorders. Although some of these channels have been well-characterized, the study of others, such as Kv3 channels, has been hindered because of limited pharmacol...
journal_title：Molecular pharmacology
pub_type： 杂志文章
doi：10.1124/mol.105.011064
更新日期：2005-05-01 00:00:00
abstract：:Microglia, as phagocytes and antigen-presenting cells in the central nervous system, are activated in such disease processes as stroke and multiple sclerosis. Because peripheral macrophages are capable of producing endocannabinoids, we have examined endocannabinoid production in a macrophage-colony stimulating factor ...
journal_title：Molecular pharmacology
pub_type： 杂志文章
doi：10.1124/mol.65.4.999
更新日期：2004-04-01 00:00:00
abstract：:Airway smooth muscle (ASM) cells can act as effector cells in the initiation and/or perpetuation of airway inflammation in asthma by producing various inflammatory chemokines or cytokines. Previous studies from our laboratory and others showed that the combination of tumor necrosis factor-alpha (TNFalpha) and interfer...
journal_title：Molecular pharmacology
pub_type： 杂志文章
doi：10.1124/mol.106.030171
更新日期：2007-02-01 00:00:00
abstract：:The action of tetrahydroaminoacridine (THA), a centrally active cholinesterase inhibitor that may provide symptomatic benefit in Alzheimer's disease, was studied on responses to the excitatory amino acid N-methyl-D-aspartate (NMDA) in cultured hippocampal neurons, using whole-cell voltage-clamp and single-channel reco...
journal_title：Molecular pharmacology
pub_type： 杂志文章
doi：
更新日期：1991-05-01 00:00:00
abstract：:A series of isoflavone and tyrphostin compounds were found to inhibit the degradation of cAMP by several cyclic nucleotide phosphodiesterase (PDE) isozymes. Specific hydroxyl groups on the isoflavone structure were critical for PDE isozyme-selective inhibition. Replacement of the C-7 hydroxyl group of the isoflavone w...
journal_title：Molecular pharmacology
pub_type： 杂志文章
doi：10.1124/mol.57.4.738
更新日期：2000-04-01 00:00:00
abstract：:In the hippocampus, two distinct forms of GABAergic inhibition have been identified, phasic inhibitory postsynaptic currents that are the consequence of the vesicular release of GABA and a tonic conductance that is activated by low ambient concentrations of extracellular GABA. It is not known what accounts for the dis...
journal_title：Molecular pharmacology
pub_type： 杂志文章
doi：10.1124/mol.63.1.2
更新日期：2003-01-01 00:00:00
abstract：:Bovine adrenal zona fasciculata (AZF) cells express a noninactivating K+ current (IAC) that sets the resting membrane potential and may mediate depolarization-dependent cortisol secretion. External ATP stimulates cortisol secretion through activation of a nucleotide receptor. In whole-cell patch clamp recordings from ...
journal_title：Molecular pharmacology
pub_type： 杂志文章
doi：10.1124/mol.55.2.364
更新日期：1999-02-01 00:00:00
abstract：:Based on their relative affinities for cholecystokinin octapeptide (26-33) (CCK-8), cholecystokinin tetrapeptide (30-33) (CCK-4), desulfated CCK-8, and gastrin, cholecystokinin (CCK) receptors have been classified as CCK-A (alimentary) and CCK-B (brain). Selective nonpeptide antagonists of CCK-A and CCK-B receptors, a...
journal_title：Molecular pharmacology
pub_type： 杂志文章
doi：
更新日期：1991-03-01 00:00:00
abstract：:The X-ray structure of the bacterial sodium channel NavAb provides a new template for the study of sodium and calcium channels. Unlike potassium channels, NavAb contains P2 helices in the outer-pore region. Because the sequence similarity between eukaryotic and prokaryotic sodium channels in this region is poor, the s...
journal_title：Molecular pharmacology
pub_type： 杂志文章
doi：10.1124/mol.112.078212
更新日期：2012-07-01 00:00:00
abstract：:Telomerase activity is expressed in most types of cancer cells but not in normal somatic cells, suggesting that telomerase may be an important target for cancer chemotherapy. Inhibition of telomerase results in telomere erosion, leading to the subsequent growth arrest of cancer cells followed by senescence or cell dea...
journal_title：Molecular pharmacology
pub_type： 杂志文章
doi：10.1124/mol.63.5.1117
更新日期：2003-05-01 00:00:00
abstract：:Acute cannabidiol treatment of mice inactivated hepatic microsomal cytochrome P-450IIIA (P-450IIIA) and markedly inhibited in vitro cannabinoid metabolism. Antibodies raised against purified P-450IIIA inhibited the microsomal formation of quantitatively minor cannabinoid metabolites but had no effect on the major meta...
journal_title：Molecular pharmacology
pub_type： 杂志文章
doi：
更新日期：1991-08-01 00:00:00
abstract：:Glucocorticoid-induced tumor necrosis factor receptor-related (GITR) protein is a costimulatory molecule that plays a role in inflammation so that GITR-Fc fusion protein can exert an anti-inflammatory effect. To investigate the mechanism by which GITR-Fc exerts its effects, we first used GITR knock-out (GITR(-/-)) mic...
journal_title：Molecular pharmacology
pub_type： 杂志文章
doi：10.1124/mol.107.044354
更新日期：2008-06-01 00:00:00
abstract：:It has been demonstrated previously that cannabinol (CBN) differentially modulates interleukin-2 (IL-2) protein secretion by T cells with a corresponding change in extracellular signal-regulated kinase activity. The objective of the present studies was to further investigate the molecular mechanism by which CBN enhanc...
journal_title：Molecular pharmacology
pub_type： 杂志文章
doi：10.1124/mol.61.2.446
更新日期：2002-02-01 00:00:00
abstract：:A polyamine component of Agelenopsis aperta spider venom designated FTX is reported to be a selective antagonist of P-type calcium channels in the mammalian brain. Consequently, this component has frequently been used as a pharmacological tool to determine the presence, distribution, and function of P-type channels in...
journal_title：Molecular pharmacology
pub_type： 杂志文章
doi：
更新日期：1996-10-01 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：:Acute desensitization of mu opioid receptors is thought to be an initial step in the development of tolerance to opioids. Given the resistance of the respiratory system to develop tolerance, desensitization of neurons in the Kölliker-Fuse (KF), a key area in the respiratory circuit, was examined. The activation of G p...
journal_title：Molecular pharmacology
pub_type： 杂志文章
doi：10.1124/mol.117.109603
更新日期：2018-01-01 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：:A functional interaction between peroxisome proliferator-activated receptor alpha (PPARalpha) and components of the circadian clock has been suggested, but whether these transcriptional factors interact to regulate the expression of their target genes remains obscure. Here we used a PPARalpha ligand, bezafibrate, to s...
journal_title：Molecular pharmacology
pub_type： 杂志文章
doi：10.1124/mol.110.064402
更新日期：2010-07-01 00:00:00
abstract：:The precise mechanism by which the cellular uptake of the endocannabinoid anandamide (AEA) occurs has been the source of much debate. In the current study, we show that neuronal differentiated CAD (dCAD) cells accumulate anandamide by a process that is inhibited in a dose-dependent manner by N-(4-hydroxyphenyl)arachid...
journal_title：Molecular pharmacology
pub_type： 杂志文章
doi：10.1124/mol.108.044834
更新日期：2008-07-01 00:00:00
abstract：:SR33557 belongs to a new class of molecules (indolizinsulfones) that act on the same receptor complex that has been characterized for other classical calcium channel effectors. The main binding properties of SR33557 to rabbit skeletal muscle are as follows. (i) Unlabeled SR33557 completely inhibits the specific bindin...
journal_title：Molecular pharmacology
pub_type： 杂志文章
doi：
更新日期：1989-06-01 00:00:00
abstract：:Interleukin 6 (IL-6), which is elevated in patients with congestive heart failure and acts as both a chronic marker of inflammation and an acute-phase reactant, is associated with myocardial damage. Circulating levels of arginine vasopressin (AVP) are elevated during cardiac stress and could be a factor for cardiac in...
journal_title：Molecular pharmacology
pub_type： 杂志文章
doi：10.1124/mol.116.107698
更新日期：2017-09-01 00:00:00
