Abstract：
:Prostaglandin synthetase has the ability to catalyze the metabolism of paracetamol to a reactive metabolite, which binds to protein and reduced glutathione (GSH). This was demonstrated with microsomes isolated from both sheep seminal vesicles (SSV) and rabbit kidney medulla. The activation of paracetamol occurred through cooxygenation during prostaglandin biosynthesis, the peroxidase activity of this enzyme being responsible for the reaction. In addition to being metabolized, paracetamol also stimulated the rate of prostaglandin biosynthesis probably by serving as a potent hydrogen donor. The metabolism of paracetamol to a reactive metabolite most likely involved the formation of a paracetamol radical species. This was indicated by an inhibitory effect of the antioxidant, butylated hydroxyanisole, as well as by a very rapid oxidation of GSH during the course of the prostaglandin synthetase catalyzed reaction. Whether this paracetamol radical is further oxidized to the quinone imine prior to reacting with GSH or protein, remains to be established. The ultimate reactive metabolite is evidently the same as that formed with liver microsomes and NADPH since the glutathione conjugates were apparently identical. The rate of paracetamol activation by SSV microsomes was, however, more than 100 times that by liver microsomes and furthermore the apparent Km was considerably lower. Finally, N-OH paracetamol was shown to be activated by prostaglandin synthetase in the presence of arachidonic acid to a metabolite apparently different from that formed from paracetamol.
journal_name
Biochem Pharmacoljournal_title
Biochemical pharmacologyauthors
Moldéus P,Andersson B,Rahimtula A,Berggren Mdoi
10.1016/0006-2952(82)90029-6subject
Has Abstractpub_date
1982-04-01 00:00:00pages
1363-8issue
7eissn
0006-2952issn
1873-2968pii
0006-2952(82)90029-6journal_volume
31pub_type
杂志文章abstract：:The formation of triacylglycerols containing fenoprofen was studied in rat isolated adipocytes and hepatocytes incubated with [3H]glycerol and R or S fenoprofen. In both hepatocytes and adipocytes there was a high-affinity enzymatic process for the synthesis of triacylglycerol containing fenoprofen which was stereospe...
journal_title：Biochemical pharmacology
pub_type： 杂志文章
doi：10.1016/0006-2952(88)90537-0
更新日期：1988-05-15 00:00:00
abstract：:Alcoholic ketoacidosis and diabetic ketoacidosis are life-threatening complications that share the characteristic features of high anion gap metabolic acidosis. Ketoacidosis is attributed in part to the massive release of ketone bodies (e.g., β-hydroxybutyrate; βOHB) from the liver into the systemic circulation. To da...
journal_title：Biochemical pharmacology
pub_type： 杂志文章
doi：10.1016/j.bcp.2018.12.005
更新日期：2019-02-01 00:00:00
abstract：:In this study, using a combination of immunological and enzymatic characterizations, we compared the forms of cytochrome P-450 induced by ethanol and glutethimide in primary cultures of chicken embryo hepatocytes. Recently we purified a cytochrome P-450 of 50K molecular weight from chicken embryo liver using glutethim...
journal_title：Biochemical pharmacology
pub_type： 杂志文章
doi：10.1016/0006-2952(89)90212-8
更新日期：1989-02-15 00:00:00
abstract：:To determine whether alpha,alpha-dideutero substitution in the side chain of the tryptamine molecule can exert primary isotope effects and enhance its bioavailability, equimolar mixtures of tryptamine (T) and either alpha,alpha-dideutero-tryptamine (alpha,alpha-[2H2]T) or beta,beta-dideutero-tryptamine (beta,beta-[2H2...
journal_title：Biochemical pharmacology
pub_type： 杂志文章
doi：10.1016/0006-2952(86)90482-x
更新日期：1986-09-01 00:00:00
abstract：:The metabolism of (1R)[1-3H]ethanol, [2-3H]lactate or [2-3H]xylitol was studied in hepatocytes from fed or T3-treated rats in the presence or absence of fructose or xylitol. The yields of tritium in ethanol, lactate, water, glycerol and glucose were determined. A simple model, describing the metabolic fate of tritium ...
journal_title：Biochemical pharmacology
pub_type： 杂志文章
doi：10.1016/0006-2952(85)90260-6
更新日期：1985-03-01 00:00:00
abstract：:Hepatocellular carcinoma (HCC) is the most common type of primary liver cancer and the fourth most frequent cause of cancer-related death worldwide. Sorafenib is the first line recommended therapy for patients with locally advanced/metastatic HCC. The low response rate is attributed to intrinsic resistance of HCC cell...
journal_title：Biochemical pharmacology
pub_type： 杂志文章
doi：10.1016/j.bcp.2020.113902
更新日期：2020-06-01 00:00:00
abstract：:Gastric cancer is the third common cause of cancer mortality in the world with poor prognosis and high recurrence due to lack of effective medicines. Our studies revealed that lanatoside C, a FDA-approved cardiac glycoside, had an anti-proliferation effect on different human cancer cell lines (MKN-45; SGC-7901; HN4; M...
journal_title：Biochemical pharmacology
pub_type： 杂志文章
doi：10.1016/j.bcp.2018.02.023
更新日期：2018-04-01 00:00:00
abstract：:We have previously reported that Gen-27, a newly synthesized flavonoid, exhibits anticancer effects against human colorectal cancer cells. In this study, we investigated the anticancer effects in human breast cancer cell lines and its underlying mechanisms. We demonstrated that Gen-27 inhibited the growth and prolifer...
journal_title：Biochemical pharmacology
pub_type： 杂志文章
doi：10.1016/j.bcp.2016.11.001
更新日期：2017-02-01 00:00:00
abstract：:Daunorubicin (DNR) is a well known anticancer drug believed to act mainly by topoisomerase II inhibition and mitochondria-mediated free radical generation. Though several studies were dedicated to elucidate the mechanism of action of DNR, however the mechanism still remains illusive. DNR is reported to affect mitochon...
journal_title：Biochemical pharmacology
pub_type： 杂志文章
doi：10.1016/j.bcp.2007.06.009
更新日期：2007-09-15 00:00:00
abstract：:The abundance of human equilibrative nucleoside transporter 1 (hENT1) has recently been shown to be a predictive marker of benefit from gemcitabine therapy in patients with pancreatic cancer. Since hENT1 is also important for the uptake of positron emission tomography (PET) tracer 3'-deoxy-3'-fluorothymidine (FLT) in ...
journal_title：Biochemical pharmacology
pub_type： 杂志文章
doi：10.1016/j.bcp.2009.09.025
更新日期：2010-02-15 00:00:00
abstract：:The binding interactions of some aryl carboxylic acid derivatives have been examined by circular dichroism and fluorescence spectroscopy. With specific probes, we have shown that the seven ligands under study bind primarily to the benzodiazepine site on HSA. Their association constants are in the range of 10(5)-10(6) ...
journal_title：Biochemical pharmacology
pub_type： 杂志文章
doi：10.1016/0006-2952(84)90668-3
更新日期：1984-07-15 00:00:00
abstract：:Escape from the proper control of the cell cycle by up-regulation of cyclins or aberrant activation of cyclin-dependent kinases (CDKs) as well as by inactivation of cellular inhibitors of CDKs (CKI) leads to malignant transformation. Loss of cellular CKIs in cancers provided a rationale for development of pharmacologi...
journal_title：Biochemical pharmacology
pub_type： 杂志文章
doi：10.1016/j.bcp.2008.07.040
更新日期：2008-12-01 00:00:00
abstract：:Novel hydroxynaphthoquinones have been shown to be potent and selective inhibitors of mitochondrial electron transport in the protozoan Eimeria tenella, inhibiting at concentrations of 10(-10) to 10(-11)M. The primary site of electron transport inhibition has been localized to the ubiquinol-cytochrome c reductase span...
journal_title：Biochemical pharmacology
pub_type： 杂志文章
doi：10.1016/0006-2952(84)90581-1
更新日期：1984-07-01 00:00:00
abstract：:Partial agonists for G protein-coupled receptors (GPCRs) provide opportunities for novel pharmacotherapies with enhanced on-target safety compared to full agonists. For the human adenosine A1 receptor (hA1AR) this has led to the discovery of capadenoson, which has been in phase IIa clinical trials for heart failure. A...
journal_title：Biochemical pharmacology
pub_type： 杂志文章
doi：10.1016/j.bcp.2020.114144
更新日期：2020-10-01 00:00:00
abstract：:Nobiletin is a polymethoxylated flavone found in certain citrus fruits that exhibits various pharmacological effects including anti-inflammatory, antitumor and neuroprotective properties. The present study investigated the effects of nobiletin on insulin sensitivity in obese diabetic ob/ob mice, and the possible mecha...
journal_title：Biochemical pharmacology
pub_type： 杂志文章
doi：10.1016/j.bcp.2010.01.034
更新日期：2010-06-01 00:00:00
abstract：:The mechanism for formation of high-affinity binding of 1-(2,6-dichlorobenzylidene-amino)-3-hydroxyguanidine (guanoxabenz) to alpha2-adrenoceptors was studied in particulate fractions from the rat spleen. The proportion of apparent high versus low-affinity alpha2-adrenoceptor binding sites increased with increasing in...
journal_title：Biochemical pharmacology
pub_type： 杂志文章
doi：10.1016/s0006-2952(98)00135-x
更新日期：1998-11-01 00:00:00
abstract：:Blocking spermidine and spermine synthesis in Plasmodium falciparum-infected erythrocytes with irreversible inhibitors of S-adenosylmethionine decarboxylase (AdoMet DC; EC 4.1.1.50), prevented the growth of the parasite in vitro. The most potent of these compounds, MDL 73811, inhibited growth of chloroquine-sensitive ...
journal_title：Biochemical pharmacology
pub_type： 杂志文章
doi：10.1016/0006-2952(91)90174-4
更新日期：1991-06-01 00:00:00
abstract：:Dexamethasone and etoposide both induce apoptosis in immature rat thymocytes. We investigated the dependence of apoptosis on the phase of the cell cycle after incubation with these drugs. Cell cycle progression was followed by a combination of pulse labelling with 5-bromo-2'-deoxyuridine (BrdU), labelling fixed cells ...
journal_title：Biochemical pharmacology
pub_type： 杂志文章
doi：10.1016/0006-2952(94)90142-2
更新日期：1994-09-15 00:00:00
abstract：:Human red blood cells and male Sprague-Dawley rats were treated in vitro and in vivo, respectively, with phenylhydrazine in order to determine whether the release of volatile hydrocarbons can serve as a suitable index for phenylhydrazine-induced red blood cell peroxidation. Lipid peroxidation following phenylhydrazine...
journal_title：Biochemical pharmacology
pub_type： 杂志文章
doi：10.1016/0006-2952(84)90338-1
更新日期：1984-06-01 00:00:00
abstract：:Diethyl esters of the glutathione S-conjugate S-p-bromobenzylglutathione, an inhibitor of glyoxalase I, and S-p-nitrobenzoxycarbonylglutathione, an inhibitor of glyoxalase II, induced growth arrest and toxicity in human leukaemia 60 cells in culture. The median growth inhibitory concentration IC50 values were 8.3 micr...
journal_title：Biochemical pharmacology
pub_type： 杂志文章
doi：10.1016/0006-2952(92)90680-h
更新日期：1992-12-15 00:00:00
abstract：:It is thought that the oxidation of low density lipoprotein (LDL) plays a key role in the pathogenesis of atherosclerosis. It is well known that lipid peroxidation reactions are propagated by peroxyl radicals and it follows, therefore, that the capacity of an individual LDL particle to scavenge these oxidants may be a...
journal_title：Biochemical pharmacology
pub_type： 杂志文章
doi：10.1016/0006-2952(93)90189-4
更新日期：1993-06-09 00:00:00
abstract：:Effects of calcein acetoxymethyl ester (calcein/AM) on macromolecular synthesis, mitochondrial membrane potential, and mode of death were studied in U-937 GTB lymphoma cells. This was accomplished by measurements of (14)C-labeled thymidine and leucine incorporation, 5,5',6,6'-tetrachloro-1,1',3, 3'-tetraethylbenzimida...
journal_title：Biochemical pharmacology
pub_type： 杂志文章
doi：10.1016/s0006-2952(00)00494-9
更新日期：2000-12-15 00:00:00
abstract：:Caco-2 cells are a widely used model in drug development to study intestinal drug transport and metabolism. Recently, serotonin (5-hydroxytryptamine, 5-HT) has been characterized as a highly selective substrate of human UDP-glucuronosyltransferase UGT1A6 [Krishnaswamy S, Duan SX, von Moltke LL, Greenblatt DJ, Court MH...
journal_title：Biochemical pharmacology
pub_type： 杂志文章
doi：10.1016/j.bcp.2005.02.010
更新日期：2005-05-01 00:00:00
abstract：:The murine Cyp2a-4 and Cyp2a-5 genes encode P450 isoforms catalysing testosterone 15 alpha-hydroxylase and coumarin 7-hydroxylase (COH) activities, respectively. Two days after the administration of a hepatotoxic dose of cerium chloride (2 mg/kg i.v.), COH activity was increased 3.2-fold in the liver of DBA/2 mice. Th...
journal_title：Biochemical pharmacology
pub_type： 杂志文章
doi：10.1016/0006-2952(92)90525-n
更新日期：1992-10-06 00:00:00
abstract：:Hep G2 cells, an established cell line derived from a human hepatoma, have retained a number of hepatocytic phase I and II reactions. The influence of picolines (2-, 3- and 4-methylpyridine), related compounds and some classical enzyme inducers on specific glutathione transferase (GST) activity and its subunit composi...
journal_title：Biochemical pharmacology
pub_type： 杂志文章
doi：10.1016/0006-2952(94)90597-5
更新日期：1994-11-16 00:00:00
abstract：:One of the most rapidly developing areas of organellar biology, and one with major involvements in biochemical pharmacology, is that of peroxisomal function. In this commentary, several recent research findings in this area are described, along with their significance in relation to the metabolism of drugs and xenobio...
journal_title：Biochemical pharmacology
pub_type： 杂志文章,评审
doi：10.1016/s0006-2952(98)00116-6
更新日期：1998-09-15 00:00:00
abstract：:The long-term effects of incubating freshly isolated, elicited guinea-pig peritoneal macrophages with the beta-adrenoceptor agonist isoprenaline and the selective inhibitor of phosphodiesterase (PDE) IV rolipram, on adenosine-3',5'-cyclic phosphate (cAMP)-specific PDE IV activity have been investigated. The level of c...
journal_title：Biochemical pharmacology
pub_type： 杂志文章
doi：10.1016/0006-2952(95)02104-3
更新日期：1995-12-22 00:00:00
abstract：:The influence of temperature on the binding of aurothiosulphate by human serum albumin was studied in unbuffered solutions at pH 7.4 and ionic strength 0.15 M by means of equilibrium dialysis. It was found that the high affinity association constant was temperature dependent. The thermodynamic characteristics of bindi...
journal_title：Biochemical pharmacology
pub_type： 杂志文章
doi：10.1016/0006-2952(86)90468-5
更新日期：1986-07-15 00:00:00
abstract：:The TRPM8 cation channel can be activated by the cooling compound icilin. Recently, we showed that stimulation of TRPM8 channels induces a signaling cascade leading to the activation of the transcription factor AP-1. Additionally, expression of the AP-1 constituent c-Fos has been shown to be induced following TRPM8 st...
journal_title：Biochemical pharmacology
pub_type： 杂志文章
doi：10.1016/j.bcp.2020.113936
更新日期：2020-07-01 00:00:00
abstract：:This Festschrift contribution summarizes the perspectives of two of David Triggle's graduate students. Both share somewhat parallel scientific and career paths-i.e., enrolling in the Biochemical Pharmacology program at the University of Buffalo, pursuing graduate training under the mentorship of David Triggle and subs...
journal_title：Biochemical pharmacology
pub_type： 历史文章,杂志文章,评审
doi：10.1016/j.bcp.2015.08.002
更新日期：2015-11-15 00:00:00
