Abstract：
:A Walker 256 rat carcinoma cell line (WR) has been shown to be resistant to a broad spectrum of bifunctional nitrogen mustards (NM) in cell culture. The parent cell line (WS) from which the WR cells were selected retains marked sensitivity to this class of drugs. Karyotype analysis showed that the parent WS had a chromosome content which was significantly higher than the WR. A number of chromosome marker bands were also distinguishable, indicative of distinct nuclear structural differences. A lack of collateral resistance to haloethylnitrosoureas was demonstrated for the WR cell line. In some cases the sensitivity of the WR to nitrosoureas was greater than that of WS. In addition, the WR could be sensitized to NM by a concomitant addition of a water-soluble carbamoylating agent, N,N'-bis(trans-4-hydroxycyclohexyl)-N'-nitrosourea, which possessed no intrinsic alkylating activity. Since NM and nitrosoureas differ pharmacologically, mainly by the latter's potential to carbamoylate, this reaction would appear to be critical to the cytotoxic properties of nitrosoureas against WR cells. Heretofore, carbamoylation has been considered of little importance to the antitumor properties of nitrosoureas. Moreover, 1-(4-amino-2-methylpyrimidine-5-yl)-methyl-3-(2-chloroethyl)-3-nitrosourea hydrochloride (ACNU) has been reported as possessing only minimal carbamoylating potential, as measured in vitro by a lysine assay. While remaining an accurate assay for the modification of the psi-amino groups of lysine, it is possible that the quantitative lysine assay may not predict the physiological carbamoylating potential of ACNU in the Walker cells, since marked cytotoxicity was achieved in both WR and WS by ACNU.
journal_name
Mol Pharmacoljournal_title
Molecular pharmacologyauthors
Tew KD,Wang ALsubject
Has Abstractpub_date
1982-05-01 00:00:00pages
729-38issue
3eissn
0026-895Xissn
1521-0111journal_volume
21pub_type
杂志文章abstract：:Glutathione-S-transferase-catalyzed conjugation of glutathione (GSH) to aflatoxin B1-8,9-epoxide plays an important role in preventing binding of this ultimate carcinogen to target macromolecules. Once formed, the aflatoxin B1-epoxide-GSH conjugates are actively extruded from the cell by an unidentified ATP-dependent ...
journal_title：Molecular pharmacology
pub_type： 杂志文章
doi：10.1124/mol.51.6.1034
更新日期：1997-06-01 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：:Previous studies indicated that activation of alpha 1-adrenergic receptors in BC3H-1 muscle cells (S. K. Ambler and P. Taylor, J. Biol. Chem. 261:5866-5871, 1986) and muscarinic receptors in 1321N1 astrocytoma cells (S. B. Masters, T. K. Harden, and J. H. Brown, Mol. Pharmacol. 27:325-332, 1985) resulted in the rapid ...
journal_title：Molecular pharmacology
pub_type： 杂志文章
doi：
更新日期：1987-09-01 00:00:00
abstract：:The gamma-aminobutyric acid (GABA) receptor type B (GABA(B)R) is constituted of at least two homologous proteins, GABA(B)R1 and GABA(B)R2. These proteins share sequence and structural similarity with metabotropic glutamate and Ca(2+)-sensing receptors, both of which are sensitive to Ca(2+). Using rat brain membranes, ...
journal_title：Molecular pharmacology
pub_type： 杂志文章
doi：10.1124/mol.57.3.419
更新日期：2000-03-01 00:00:00
abstract：:We have previously reported that, depending on the dose, nitric oxide (NO)-generating agents exert a dual facilitatory and inhibitory action on glutamatergic transmission on the rostral ventrolateral medulla (RVLM) neurons. The molecular mechanisms underlying the NO-mediated synaptic inhibition have not yet been defin...
journal_title：Molecular pharmacology
pub_type： 杂志文章
doi：10.1124/mol.104.000554
更新日期：2004-09-01 00:00:00
abstract：:The current study was designed to investigate the importance of cationic amino acid transporters (CATs) for the L-arginine supply to nitric oxide (NO) synthases in mouse J774A.1 macrophages and human EA.hy926 endothelial cells. CAT-1 was expressed in both cell types, whereas CAT-2B was only expressed in activated macr...
journal_title：Molecular pharmacology
pub_type： 杂志文章
doi：
更新日期：2000-01-01 00:00:00
abstract：:Ribavirin used in therapies against hepatitis C virus (HCV) is potentially efficient against other viruses but presents a high cytotoxicity. Several ribavirin triphosphate analogs modified on the ribose moiety were synthesized and tested in vitro on the RNA polymerases of HCV, phage T7, and HIV-1 reverse transcriptase...
journal_title：Molecular pharmacology
pub_type： 杂志文章
doi：10.1124/mol.63.3.538
更新日期：2003-03-01 00:00:00
abstract：:In the present study we have investigated the capacity of various compounds sterically related to indolo[3,2-b]carbazole to inhibit specific 2,3,7,8-tetrachloro[1,6-3H]dibenzo-p-dioxin binding in rat liver cytosol, as analyzed by electrofocusing in polyacrylamide gels. When the two nitrogen atoms of indolo[3,2-b]carba...
journal_title：Molecular pharmacology
pub_type： 杂志文章
doi：
更新日期：1993-08-01 00:00:00
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)],...
journal_title：Molecular pharmacology
pub_type： 杂志文章
doi：10.1124/mol.105.017756
更新日期：2006-03-01 00:00:00
abstract：:2,3,7,8-Tetrachlorodibenzo-p-dioxin (TCDD) suppresses many immune responses, both innate and adaptive. Suppression is mediated by the aryl hydrocarbon receptor (AhR), a ligand-activated transcription factor. The AhR mediates TCDD toxicity presumably through the alteration of transcriptional events, either by promoting...
journal_title：Molecular pharmacology
pub_type： 杂志文章
doi：10.1124/mol.62.3.722
更新日期：2002-09-01 00:00:00
abstract：:In the present study, we have elucidated the functional characteristics and mechanism of action of methaqualone (2-methyl-3-o-tolyl-4(3H)-quinazolinone, Quaalude), an infamous sedative-hypnotic and recreational drug from the 1960s-1970s. Methaqualone was demonstrated to be a positive allosteric modulator at human α1,2...
journal_title：Molecular pharmacology
pub_type： 杂志文章
doi：10.1124/mol.115.099291
更新日期：2015-08-01 00:00:00
abstract：:Maurotoxin (MTX) is a potent blocker of human voltage-activated Kv1.2 and intermediate-conductance calcium-activated potassium channels, hIKCa1. Because its blocking affinity on both channels is similar, although the pore region of these channels show only few conserved amino acids, we aimed to characterize the bindin...
journal_title：Molecular pharmacology
pub_type： 杂志文章
doi：10.1124/mol.104.002774
更新日期：2004-11-01 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：:Beta-L-dioxolane-cytidine (L-OddC, BCH-4556, Troxacitabine), a novel L-configuration deoxycytidine analog, is under phase III clinical trial for cancer treatment. We showed that human apurinic/apyrimidinic endonuclease (APE-1) has exonuclease activity for preferentially removing L-OddC and other L-configuration nucleo...
journal_title：Molecular pharmacology
pub_type： 杂志文章
doi：10.1124/mol.105.021527
更新日期：2006-05-01 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：:Several structurally related series of folate analogs were studied as substrates for mouse liver folylpolyglutamate synthetase (FPGS). A comparison of the kinetics of the interaction of this enzyme with folate analogs that contained the quinazoline ring in place of the pteridine ring with those of the analogous pterid...
journal_title：Molecular pharmacology
pub_type： 杂志文章
doi：
更新日期：1989-11-01 00:00:00
abstract：:Mitochondrial disorders are devastating genetic diseases for which efficacious therapies are still an unmet need. Recent studies report that increased availability of intracellular NAD obtained by inhibition of the NAD-consuming enzyme poly(ADP-ribose) polymerase (PARP)-1 or supplementation with the NAD-precursor nico...
journal_title：Molecular pharmacology
pub_type： 杂志文章
doi：10.1124/mol.114.097204
更新日期：2015-06-01 00:00:00
abstract：:Post-transcriptional protein synthesis by GH3 cloned pituitary cells, which secrete prolactin and growth hormone, is dependent on Ca2+. The effects of antagonists of prolactin secretion were examined on overall protein synthesis in GH3 cells as a function of cellular Ca2+ depletion and restoration at varying concentra...
journal_title：Molecular pharmacology
pub_type： 杂志文章
doi：
更新日期：1986-04-01 00:00:00
abstract：:Previous studies have shown that at least two subtypes of somatostatin (SRIF) receptors (SRIF1 and SRIF2) are expressed in mammalian cells. SRIF1 receptors have high affinity for MK 678, whereas SRIF2 receptors have no affinity for MK 678 but selectively bind peptides with structures similar to that of CGP 23996. Rece...
journal_title：Molecular pharmacology
pub_type： 杂志文章
doi：
更新日期：1992-07-01 00:00:00
abstract：:SC-54628 [1-(2-methylphenyl)-4-butyl-1,3-dihydro-3-[[6-[2-(1H- tetrazol-5-yl)phenyl]-3-pyridinyl]methyl]-2H-imidazol-2-one] and its 1-(2,6-dimethylphenyl)-2H-imidazol-2-one derivative SC-54629 were potent inhibitors of 125I-angiotensin II (125I-AII) binding to rat adrenal cortex angiotensin type 1 (AT1) receptors. SC-...
journal_title：Molecular pharmacology
pub_type： 杂志文章
doi：
更新日期：1995-01-01 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
abstract：:Depending on their primary structure, the 28 mammalian transient receptor potential (TRP) cation channels identified so far can be sorted into 6 subfamilies: TRPC ("Canonical"), TRPV ("Vanilloid"), TRPM ("Melastatin"), TRPP ("Polycystin"), TRPML ("Mucolipin"), and TRPA ("Ankyrin"). The TRPV subfamily (vanilloid recept...
journal_title：Molecular pharmacology
pub_type： 杂志文章,评审
doi：10.1124/mol.109.055624
更新日期：2009-06-01 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 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
abstract：:The cytotoxic efficacy of antitumor drugs targeted at DNA topoisomerase II (topo II) in many cases varies in direct proportion to cellular topo II content. To investigate the transcriptional control of the predominant alpha form of topo II, the 5' flanking region of the human topo II alpha gene (positions -562 to +90)...
journal_title：Molecular pharmacology
pub_type： 杂志文章
doi：
更新日期：1995-04-01 00:00:00
abstract：:The nuclear pregnane X receptor (PXR) and constitutive androstane receptor (CAR) play central roles in protecting the body against environmental chemicals (xenobiotics). PXR and CAR are activated by a wide range of xenobiotics and regulate cytochrome P450 and other genes whose products are involved in the detoxificati...
journal_title：Molecular pharmacology
pub_type： 杂志文章
doi：10.1124/mol.62.3.638
更新日期：2002-09-01 00:00:00
abstract：:The effect of halothane on synthesis of retained and secreted proteins was investigated using isolated perfused rat livers. Anesthetic exposure rapidly inhibited synthesis of total liver proteins in a dose-dependent manner by a mechanism which appeared to involve reduced rates of both peptide chain initiation and elon...
journal_title：Molecular pharmacology
pub_type： 杂志文章
doi：
更新日期：1983-09-01 00:00:00
abstract：:The effects of tournefolic acid B (TAB) and two ester derivatives, TAB methyl ester (TABM) and TAB ethyl ester (TABE), on N-methyl-D-aspartate (NMDA)-mediated excitotoxicity and the underlying mechanisms were investigated. Treatment with 50 microM NMDA elicited neuronal death by 48.7 +/- 5.1%, coinciding with the appe...
journal_title：Molecular pharmacology
pub_type： 杂志文章
doi：10.1124/mol.105.018770
更新日期：2006-03-01 00:00:00
abstract：:Neuromedin U (NmU) is a 25 amino acid peptide prominently expressed in the upper gastrointestinal (GI) tract and central nervous system. It is highly conserved throughout evolution and induces smooth muscle contraction in a variety of species. Our understanding of NmU biology has been limited because the identity of i...
journal_title：Molecular pharmacology
pub_type： 杂志文章
doi：10.1124/mol.58.4.870
更新日期：2000-10-01 00:00:00
abstract：:The subunit composition and pharmacological regulation of rat neuronal nicotinic cholinergic receptors were assessed. Specific immunoprecipitation was determined in solubilized rat brain homogenates using [3H]cytisine, a high affinity agonist at nicotinic receptors, in conjunction with polyclonal antisera generated ag...
journal_title：Molecular pharmacology
pub_type： 杂志文章
doi：
更新日期：1992-01-01 00:00:00
