Abstract:
:N-Nitrosoguanidines are potential carcinogens. However, the toxicity of these agents is attenuated significantly in laboratory rodents by processes that remove the nitroso group to generate the relatively innocuous parent guanidinium compound. The denitrosation of 1,3-dimethyl-2-cyano-1-nitrosoguanidine (CyanoDMNG) mediated by rat hepatocytes in primary culture was investigated. At concentrations < or = 200 microM, applied CyanoDMNG was converted efficiently to 1,3-dimethyl-2-cyanoguanidine (CyanoDMG). In trials using 50 microM CyanoDMNG (5 mL dosing solutions), it was demonstrated that hepatocytes are capable of denitrosating a 40 microM concentration of the applied compound with little change in the total or oxidized glutathione levels. The process was inhibited by coincidently applied ethacrynic acid, a glutathione transferase inhibitor. Reduction of hepatocyte glutathione to 20% of control levels by buthionine sulfoximine pretreatment had little effect on CyanoDMG production; total depletion of cytosolic glutathione by diethyl maleate pretreatment arrested CyanoDMNG processing. Hepatocyte-mediated CyanoDMNG denitrosation did not generate nitrite; nitrate yields were 10% relative to the CyanoDMG produced. The mercuric chloride/azo dye response of cultures lysed at times during 50 microM CyanoDMNG processing indicated intact CyanoDMNG as the only dye-sensitive material present. At applied CyanoDMNG > 100 microM, S-nitrosoglutathione (GSNO) yields were detectable; 4 microM GSNO was generated (concentration in 5 mL lysates) and maintained during 60 min at the 200 microM CyanoDMNG treatment level; this yield decayed if CyanoDMNG was withdrawn. Based on these and previous findings, it is hypothesized that CyanoDMNG is converted to CyanoDMG and GSNO by glutathione transferases and that GSNO is catabolized to eventually regenerate reduced glutathione. The fate of most of the NO moiety released remains to be determined.
journal_name
Biochem Pharmacoljournal_title
Biochemical pharmacologyauthors
Jensen DE,Belka GK,Dworkin Cdoi
10.1016/s0006-2952(96)00861-1subject
Has Abstractpub_date
1997-05-09 00:00:00pages
1297-306issue
9eissn
0006-2952issn
1873-2968pii
S0006-2952(96)00861-1journal_volume
53pub_type
杂志文章abstract:BACKGROUND AND PURPOSE:Chronic nicotine exposure upregulates α4β2* nicotinic acetylcholine receptors (nAChRs) in the brain. The goal of this study was to examine the role of three serine residues in the large cytoplasmic loop of the α4 subunit on α4β2* upregulation in neurons. EXPERIMENTAL APPROACH:Serine residues S33...
journal_title:Biochemical pharmacology
pub_type: 杂志文章
doi:10.1016/j.bcp.2018.11.008
更新日期:2019-01-01 00:00:00
abstract::Short-term agonist-induced loss of cell surface muscarinic receptors and desensitization of receptor-mediated cyclic GMP (cGMP) formation and phosphoinositide hydrolysis were examined in mouse neuroblastoma cells (clone N1E-115) in suspension. This treatment resulted in a time-dependent reduction of approximately 40% ...
journal_title:Biochemical pharmacology
pub_type: 杂志文章
doi:10.1016/0006-2952(89)90418-8
更新日期:1989-06-01 00:00:00
abstract::Human recombinant superoxide dismutase (SOD) was modified into a mannosylated form (Man-SOD), and its cellular uptake and inhibitory effect on superoxide anion release were studied in vitro, using cultured mouse peritoneal macrophages. [111In]Man-SOD was taken up by the macrophages to a great extent, whereas no signif...
journal_title:Biochemical pharmacology
pub_type: 杂志文章
doi:10.1016/0006-2952(94)90485-5
更新日期:1994-03-02 00:00:00
abstract::A new analogue of methotrexate was synthesized from 4-amino-4-deoxy-N10-methylpteroic acid and D,L-homocysteic acid. The product (mAPA-HCysA) was bound tightly to L1210 mouse leukemia dihydrofolate reductase (IC50 = 1 nM), inhibited L1210 cell proliferation in culture (IC50 = 0.3 microM), and prolonged the survival of...
journal_title:Biochemical pharmacology
pub_type: 杂志文章
doi:10.1016/0006-2952(84)90383-6
更新日期:1984-01-01 00:00:00
abstract::Hyperactivated macrophages play a key role in the initiation and perpetuation of mucosal inflammation in Crohn's disease (CD). Increasing evidence suggests that the basic helix-loop-helix (bHLH) repressor Twist1 can suppress activation of nuclear factor-κB (NF-κB) and the subsequent production of TNF-α, which are both...
journal_title:Biochemical pharmacology
pub_type: 杂志文章
doi:10.1016/j.bcp.2018.07.020
更新日期:2018-09-01 00:00:00
abstract::Nuclear factor-kappaB (NF-kappaB) activity affects cell survival and determines the sensitivity of cancer cells to cytotoxic agents as well as to ionizing radiation. Preventing the protective function of NF-kappaB may result in chemo- and radio-sensitization of cancer cells. Therefore, NF-kappaB has emerged as one of ...
journal_title:Biochemical pharmacology
pub_type: 杂志文章,评审
doi:10.1016/s0006-2952(98)00224-x
更新日期:1999-01-01 00:00:00
abstract::The in vitro inhibition of the cytochrome P-450 (P-450) isozyme specific positional hydroxylation of androst-4-ene-3,17-dione (androstenedione) by the alkylamino containing compounds trans- and cis-tamoxifen, 4-hydroxytamoxifen, N-desmethyltamoxifen, SKF 525-A and the non-alkylamino containing compounds tamoxifen meta...
journal_title:Biochemical pharmacology
pub_type: 杂志文章
doi:10.1016/0006-2952(89)90168-8
更新日期:1989-01-01 00:00:00
abstract::Epidemiological and experimental animal data indicate that exposure to both metals and metalloid species exacerbates the risk of human diseases, particularly cancers. Vascular endothelial growth factor (VEGF), which performs a primary function in both tumor progression and angiogenesis, is up-regulated due to exposure...
journal_title:Biochemical pharmacology
pub_type: 杂志文章
doi:10.1016/j.bcp.2006.03.021
更新日期:2006-06-28 00:00:00
abstract::Most of diabetic cardiovascular complications are attributed to endothelial dysfunction and impaired angiogenesis. Endoplasmic Reticulum (ER) and oxidative stresses were shown to play a pivotal role in the development of endothelial dysfunction in diabetes. Hemeoxygenase-1 (HO-1) was shown to protect against oxidative...
journal_title:Biochemical pharmacology
pub_type: 杂志文章
doi:10.1016/j.bcp.2016.12.009
更新日期:2017-03-01 00:00:00
abstract::A marked genetic variation in the capacity to perform xenobiotic metabolism was observed in microsomal fractions from the seven Drosophila strains studied. A 1,5 to 2-fold variation was found in the content of cytochrome P-450 and in the NADPH-cytochrome c reductase activity. The two insecticide-resistant strains Hiko...
journal_title:Biochemical pharmacology
pub_type: 杂志文章
doi:10.1016/0006-2952(84)90364-2
更新日期:1984-01-01 00:00:00
abstract::Interleukin (IL)-22 plays protective roles in infections and in inflammatory diseases that have been linked to its meditation of innate immunity via multiple mechanisms. IL-22 binds specifically to its heterodimeric receptor, which is expressed on a variety of epithelial tissues. UTTR1147A is a recombinant fusion prot...
journal_title:Biochemical pharmacology
pub_type: 杂志文章
doi:10.1016/j.bcp.2018.03.031
更新日期:2018-06-01 00:00:00
abstract::Clinical long-term neuroleptic administration induces extrapyramidal motor side-effects, of which tardive dyskinesia is the most important. Experimentally, dopamine D2 supersensitivity is observed after phenothiazine and butyrophenone treatment. Neuroleptic-induced tardive dyskinesia and D2 modulation have been linked...
journal_title:Biochemical pharmacology
pub_type: 杂志文章
doi:10.1016/0006-2952(95)02187-6
更新日期:1996-02-09 00:00:00
abstract::An important pathologic hallmark of Alzheimer's disease (AD) is neuroinflammation, a process characterized in AD by disproportionate activation of cells (microglia and astrocytes, primarily) of the non-specific innate immune system within the CNS. While inflammation itself is not intrinsically detrimental, a delicate ...
journal_title:Biochemical pharmacology
pub_type: 杂志文章,评审
doi:10.1016/j.bcp.2013.12.014
更新日期:2014-04-15 00:00:00
abstract::Ethyl 2[5(4-chlorophenyl)pentyl]oxirane-2-carboxylate (POCA) is strongly hypoglycaemic in fasted normal and diabetic rats [H. P. O. Wolf, K. Eistetter and G. Ludwig, Diabetologia 22, 456 (1982)]. POCA was fed for 12 weeks to rats on a standard low-fat (3%) diet at levels of 0.05% and 0.2% to give daily intakes of abou...
journal_title:Biochemical pharmacology
pub_type: 杂志文章
doi:10.1016/0006-2952(84)90242-9
更新日期:1984-02-01 00:00:00
abstract::"Are new neurons added in the adult mammalian brain?" "Do neural stem cells activate following CNS diseases?" "How can we modulate their activation to promote recovery?" Recent findings in the field provide novel insights for addressing these questions from a new perspective. In this review, we will summarize the curr...
journal_title:Biochemical pharmacology
pub_type: 杂志文章,评审
doi:10.1016/j.bcp.2017.07.003
更新日期:2017-10-01 00:00:00
abstract::The aim of the present study was to investigate the effects of myricitrin, a flavonoid with anti-inflammatory and antinociceptive action, upon persistent neuropathic and inflammatory pain. The neuropathic pain was caused by a partial ligation (2/3) of the sciatic nerve and the inflammatory pain was induced by an intra...
journal_title:Biochemical pharmacology
pub_type: 杂志文章
doi:10.1016/j.bcp.2006.08.028
更新日期:2006-12-15 00:00:00
abstract::In order to understand the relationship between the free ionized calcium concentration in the axon terminals and the transmitter release we have investigated the effect of ruthenium red (RuR) and m-chloro-carbonylcyanide phenyl hydrazon (CCCP), mitochondrial uncoupler agents on the liberation of acetylcholine from mye...
journal_title:Biochemical pharmacology
pub_type: 杂志文章
doi:10.1016/0006-2952(87)90020-7
更新日期:1987-11-01 00:00:00
abstract::Purified red blood cell cytosol is able to activate 2-aminofluorene (2AF) to N-hydroxy-2-aminofluorene. Apparent kinetic parameters are determined with and without methylene blue. The latter, which maintains haemoglobin in the reduced form and stimulates NADPH production, increases the affinity of the enzyme for the 2...
journal_title:Biochemical pharmacology
pub_type: 杂志文章
doi:10.1016/0006-2952(92)90691-b
更新日期:1992-12-15 00:00:00
abstract::Membranes of neuroblastoma N1E-115 cells contain a specific protein carboxyl methyltransferase that methylates a 70 kD protein and a group of 21-23 kD proteins which are tightly bound to the membranes. The enzyme catalyzes the transfer of [methyl-3H] groups from [methyl-3H]S-adenosyl-L-methionine (Km = 0.22 microM) to...
journal_title:Biochemical pharmacology
pub_type: 杂志文章
doi:10.1016/0006-2952(90)90405-a
更新日期:1990-09-15 00:00:00
abstract::The development of pharmacological and biological inhibitors of receptor tyrosine kinases (RTKs) has changed the treatment paradigm of several neoplastic diseases. However, the occurrence of intrinsic and acquired resistance represents a limit to the efficacy of these drugs even in RTK-addicted cancers. The identifica...
journal_title:Biochemical pharmacology
pub_type: 杂志文章,评审
doi:10.1016/j.bcp.2020.114084
更新日期:2020-08-01 00:00:00
abstract::F 11782, or 2',3'-bis-pentafluorophenoxyacetyl-4',6'-ethylidene-beta-D-glucoside of 4'-phosphate-4'-dimethylepipodophyllotoxin 2-N-methyl glucamine salt, a novel dual catalytic inhibitor of topoisomerases I and II, was identified as a potent inhibitor of nucleotide excision repair (NER) by screening procedures using t...
journal_title:Biochemical pharmacology
pub_type: 杂志文章
doi:10.1016/s0006-2952(01)00835-8
更新日期:2002-01-15 00:00:00
abstract::The effects of taurine (2-aminoethanesulphonic acid) and its analogues, 2-aminoethylarsonic acid, 2-hydroxyethanesulphonic (isethionic) acid, 3-aminopropanesulphonic acid, 2-aminoethylphosphonic acid, and N,N-dimethyltaurine, were studied on the transport of Ca2+ by mitochondria isolated from rat liver. Taurine enhanc...
journal_title:Biochemical pharmacology
pub_type: 杂志文章
doi:10.1016/s0006-2952(99)00183-5
更新日期:1999-10-01 00:00:00
abstract::The crude mitochondrial fraction of rat brain contains an active dehydrogenase involved in the direct oxidation of gamma-aminobutyric acid. INT (p-iodonitrotetrazolium violet) can serve as an efficient acceptor of electrons in this dehydrogenase reaction. During this oxidation of GABA, ammonia is not produced. In vitr...
journal_title:Biochemical pharmacology
pub_type: 杂志文章
doi:10.1016/0006-2952(82)90553-6
更新日期:1982-10-15 00:00:00
abstract::The effects of injections of a synthetic adrenocorticotropin (ACTH 1-17, Synchrodyn) on the rate of DNA labeling in the metaphyseal bone of CD2F1 mice were tested on a chronopharmacological dosing schedule. Groups of mice that had been conditioned to a 12-hr light/12-hr dark schedule were injected at one of six differ...
journal_title:Biochemical pharmacology
pub_type: 杂志文章
doi:10.1016/0006-2952(85)90494-0
更新日期:1985-04-15 00:00:00
abstract::Hepatic microsomal preparations from male and female rats were delipidated by column chromatography following cholate solubilisation. The enzyme activities were reconstituted using known lipids and the vesicle reconstitution method. Enzyme activity was assayed using lignocaine as the substrate for the mixed function o...
journal_title:Biochemical pharmacology
pub_type: 杂志文章
doi:10.1016/0006-2952(87)90071-2
更新日期:1987-04-15 00:00:00
abstract::The carboxylesterase activity in both plasma and liver of guinea-pig were separated into three main peaks by chromatofocusing. Two of the three plasma enzymes were retained by affinity chromatography on Affi-Gel Blue (100-200 mesh). Isoelectric points determined by chromatofocusing or isoelectrofocusing were pI 6.1, p...
journal_title:Biochemical pharmacology
pub_type: 杂志文章
doi:10.1016/0006-2952(87)90461-8
更新日期:1987-11-15 00:00:00
abstract::We have studied the effects of the recently reported two new metabolites of the antitumor agent VP-16-213, the ortho-dihydroxy derivative or catechol and the ortho-quinone, on the biological activity of single-stranded and double-stranded phi X174 DNA, the binding of the metabolites to calf thymus DNA and the conversi...
journal_title:Biochemical pharmacology
pub_type: 杂志文章
doi:10.1016/0006-2952(88)90388-7
更新日期:1988-10-01 00:00:00
abstract::ATP-driven efflux pumps such as phosphoglycoprotein-170 (P-gp), multidrug-resistance-associated protein-2 (MRP-2), or breast cancer resistance protein (BCRP) play a crucial role in limiting the efficacy of tumor pharmacotherapy. Selected flavonoids have been suggested to inhibit individual efflux-transporters and to a...
journal_title:Biochemical pharmacology
pub_type: 杂志文章
doi:10.1016/j.bcp.2010.04.038
更新日期:2010-08-15 00:00:00
abstract::Alzheimer's disease (AD), the most common form of dementia, is characterized by the deposition of amyloid plaques, accumulation of fibrillary tangles in neurons, neurite degeneration, loss of neurons, and a progressive loss of cognitive function. The pathogenesis of AD is not fully understood, and no strong disease-mo...
journal_title:Biochemical pharmacology
pub_type: 杂志文章,评审
doi:10.1016/j.bcp.2011.06.040
更新日期:2011-11-15 00:00:00
abstract::Several drug compounds have failed in clinical trials due to extensive biotransformation by aldehyde oxidase (AOX) (EC 1.2.3.1). One of the main reasons is the difficulty in scaling clearance for drugs metabolised by AOX, from preclinical species to human. Using methotrexate as a probe substrate, we evaluated AOX meta...
journal_title:Biochemical pharmacology
pub_type: 杂志文章
doi:10.1016/j.bcp.2015.05.010
更新日期:2015-08-01 00:00:00