Abstract：
:Phosphodiesterase inhibitors were used as a tool to manipulate cellular nucleotide levels in vitro and in vivo. The lipopolysaccharide (LPS)-induced release of tumor necrosis factor alpha (TNF-alpha) from mouse peritoneal macrophages was inhibited by prostaglandin E2 with an IC50 of 0.05 microM and by dibutyryl-cAMP with an IC50 of 180 microM. In the presence of the phosphodiesterase inhibitors zardaverine or rolipram the intracellular cAMP concentration of LPS-stimulated macrophages was significantly increased. In these cells, LPS-inducible TNF release was inhibited by zardaverine (IC50 = 1.5 microM) or by rolipram (IC50 = 0.35 microM). In a model of septic shock, i.e. LPS challenge of galactosamine-sensitized mice, a dose-dependent protection against liver injury was observed following oral application of rolipram (ED50 = 0.55 mg/kg) or of zardaverine (ED50 approximately 30 mg/kg). The adenylate cyclase activator forskolin was also protective. Rolipram also protected against TNF-induced liver injury in mice while zardaverine failed to do so. It is concluded that the intracellular cAMP level of macrophages is a critical determinant of LPS-inducible TNF release and therefore modulates the susceptibility to septic shock.
journal_name
Biochem Pharmacoljournal_title
Biochemical pharmacologyauthors
Fischer W,Schudt C,Wendel Adoi
10.1016/0006-2952(93)90219-msubject
Has Abstractpub_date
1993-06-22 00:00:00pages
2399-404issue
12eissn
0006-2952issn
1873-2968pii
0006-2952(93)90219-Mjournal_volume
45pub_type
杂志文章abstract：:Several aspects of the effects of zinc on the metabolism of glutathione were examined in the Chinese hamster cell (line CHO) and in three derived sublines which differ in their resistance to the thiol reactive heavy metal cadmium. In the parental CHO cell, which does not induce the synthesis of metallothionein in resp...
journal_title：Biochemical pharmacology
pub_type： 杂志文章
doi：10.1016/0006-2952(83)90243-5
更新日期：1983-10-15 00:00:00
abstract：:The present study investigated the mechanism by which theophylline decreases cis-diamminedichloroplatinum(II) (DDP)-induced DNA crosslinking in L1210 cells. Alkaline elution of DNA from L1210 cells treated with DDP in the presence and absence of 1 mM theophylline showed that theophylline decreased interstrand crosslin...
journal_title：Biochemical pharmacology
pub_type： 杂志文章
doi：10.1016/0006-2952(86)90355-2
更新日期：1986-02-15 00:00:00
abstract：:The Na+/K(+)-pump activity and the utilization of adenosine triphosphate (ATP) were studied in rat peritoneal mast cells after histamine secretion induced by compound 48/80. We measured the ouabain-sensitive K(+)-uptake by a radioactive technique (86Rb+). The ATP content and the glycolytic ATP-production were measured...
journal_title：Biochemical pharmacology
pub_type： 杂志文章
doi：10.1016/0006-2952(94)90299-2
更新日期：1994-05-18 00:00:00
abstract：:The present study was undertaken to investigate a mechanism of the inhibitory effect of vitamin E in urethane-induced lung tumorigenesis in mice. We assayed ornithine decarboxylase (ODC) activity and the prostaglandin E2 (PGE2) level in lung at 8 weeks after urethane injection (promotion phase). Excessive vitamin E fe...
journal_title：Biochemical pharmacology
pub_type： 杂志文章
doi：10.1016/s0006-2952(96)00869-6
更新日期：1997-06-01 00:00:00
abstract：:Understanding the receptor activation mechanism is essential for the rational design of pharmacologically active ligand molecules. However, the activation mechanism of most cytokine receptors remains still unclear, and while agonism and antagonism have been described for ligand-mimetic peptides, there has been no repo...
journal_title：Biochemical pharmacology
pub_type： 杂志文章
doi：10.1016/j.bcp.2004.04.014
更新日期：2004-08-01 00:00:00
abstract：:The effects of physiological and pathological concentrations of glucocorticoids were investigated using the glucocorticoid antagonist RU486 and the synthetic glucocorticoid dexamethasone, respectively. The effects of these treatments on the concentrations of glutamine and other amino acids in skeletal muscle and plasm...
journal_title：Biochemical pharmacology
pub_type： 杂志文章
doi：10.1016/0006-2952(90)90505-f
更新日期：1990-09-01 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：:Intact brain cell aggregates were dissociated from adult rat brains, by a simple sieving technique, and were used to study the binding characteristics of [3H]N-methylscopolamine to muscarinic acetylcholine receptors. The magnitude of binding of this ligand was related linearly to the amount of cell protein in the bind...
journal_title：Biochemical pharmacology
pub_type： 杂志文章
doi：10.1016/0006-2952(85)90288-6
更新日期：1985-12-15 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：:Human flavin-dependent monooxygenase (FMO) isoforms 1 and 3 were expressed by retroviral gene transfer in mouse C3H/10T1/2 cells. FMO function was determined by the sulfoxidation of p-tolylmethylsulfide (TMS). Enzyme activity ranged from 4 to 30 nmol p-tolylmethylsulfoxide (TMSO)/30 min/mg cell protein for FMO 3 clone...
journal_title：Biochemical pharmacology
pub_type： 杂志文章
doi：10.1016/s0006-2952(02)00978-4
更新日期：2002-06-01 00:00:00
abstract：:ABT-263 induces MCL1 upregulation in cancer cells, which confers resistance to the drug. An increased understanding of the mechanism underlying ABT-263-induced MCL1 expression may provide a strategy to improve its tumor-suppression activity. The present study revealed that ABT-263 reduced the turnover of MCL1 mRNA, th...
journal_title：Biochemical pharmacology
pub_type： 杂志文章
doi：10.1016/j.bcp.2020.114047
更新日期：2020-08-01 00:00:00
abstract：:Incubation of human carcinoma cells with mitoxantrone resulted in an intracellular distribution of the drug into cytoplasmic, nuclear and cytoskeletal compartments occurring within 1 min of drug treatment. Incubation of the cells in drug-free medium resulted in an efflux of the drug such that 80% of the intracellular ...
journal_title：Biochemical pharmacology
pub_type： 杂志文章
doi：10.1016/0006-2952(89)90527-3
更新日期：1989-12-01 00:00:00
abstract：:Sorafenib is the only FDA approved drug for the treatment of advanced hepatocellular carcinoma (HCC) and other malignancies. Studies indicate that TGF-β signalling is associated with tumour progression in HCC. Autocrine and paracrine TGF-β promotes tumour growth and malignancy by inducing epithelial-mesenchymal transi...
journal_title：Biochemical pharmacology
pub_type： 杂志文章
doi：10.1016/j.bcp.2018.04.014
更新日期：2018-08-01 00:00:00
abstract：:Endomorphin-2 (Tyr-Pro-Phe-PheNH(2)) was discovered as an endogenous ligand for the mu-opioid receptor. The physiological function of endomorphin-2 as a neurotransmitter or neuromodulator may cease through the rapid enzymatic process in the synapse of brain, as for other neuropeptides. The present study was conducted ...
journal_title：Biochemical pharmacology
pub_type： 杂志文章
doi：10.1016/s0006-2952(03)00391-5
更新日期：2003-08-15 00:00:00
abstract：:The growth inhibitory effects of 5-fluorouracil (FUra) or 5-fluoro-2'-deoxyuridine (FdUrd) combined with 5-methyltetrahydrofolate (5-CH3-H4PteGlu) were determined, as a function of time, dose, and sequence of exposure, on human T-lymphoblast leukemia cells, CCRF-CEM. Synergistic inhibitory effects on cell growth were ...
journal_title：Biochemical pharmacology
pub_type： 杂志文章
doi：10.1016/0006-2952(87)90201-2
更新日期：1987-09-15 00:00:00
abstract：:[Carboxyl-14C] labelled 1,2,3,4-tetrahydro-beta-carboline-1-carboxylic acid (I) and 1-methyl-1,2,3,4-tetrahydro-beta-carboline-1-carboxylic acid (II) were synthesized and their decarboxylation was studied in mouse brain homogenate and buffer. The decarboxylation rates of (I) and (II) in the homogenate were about 6-fol...
journal_title：Biochemical pharmacology
pub_type： 杂志文章
doi：10.1016/0006-2952(86)90173-5
更新日期：1986-08-15 00:00:00
abstract：:Knowledge of the nature of the interaction between the stimulatory G protein (Gs) and the adenylyl cyclase catalytic unit (C) is essential for interpreting the effects of Gs mutations and expression levels on cellular response to a wide variety of hormones, drugs, and neurotransmitters. It has been proposed that beta-...
journal_title：Biochemical pharmacology
pub_type： 杂志文章
doi：10.1016/s0006-2952(97)00148-2
更新日期：1997-07-01 00:00:00
abstract：:Recently, accumulated statistical data indicate the protective effect of caffeine consumption against several types of cancer diseases. There are also reports about protective effect of caffeine and other xanthines against tumors induced by polycyclic aromatic hydrocarbons. One of the explanations is based on biologic...
journal_title：Biochemical pharmacology
pub_type： 杂志文章
doi：10.1016/s0006-2952(01)00904-2
更新日期：2002-02-15 00:00:00
abstract：:An Ehrlich ascites tumour cell line (EHR2) was selected for resistance to etoposide (VP16) by in vivo exposure to this agent. The resulting cell line (EHR2/VP16) was 114.3-, 5.7-, and 4.0-fold resistant to VP16, daunorubicin, and vincristine, respectively. The amount of salt-extractable immunoreactive topoisomerase II...
journal_title：Biochemical pharmacology
pub_type： 杂志文章
doi：10.1016/s0006-2952(00)00338-5
更新日期：2000-08-01 00:00:00
abstract：:We have studied the effect of the protein phosphatase (PP) inhibitor, okadaic acid (OKA) on histamine release elicited by immunologic and non-immunologic stimuli in peritoneal and pleural rat mast cells. When cells were stimulated with antigen (egg albumin), OKA strongly inhibited histamine release. This finding sugge...
journal_title：Biochemical pharmacology
pub_type： 杂志文章
doi：10.1016/0006-2952(94)90194-5
更新日期：1994-02-09 00:00:00
abstract：:Tetraalkylammonium salts having n-propyl to n-amyl side chains inhibited rat liver sulfotransferase (ST) activities toward dehydroepiandrosterone and cortisol, but not ST activity toward 2-naphthol, whereas trialkylamines having ethyl to n-amyl side chains inhibited ST activity toward dehydroepiandrosterone, but not S...
journal_title：Biochemical pharmacology
pub_type： 杂志文章
doi：10.1016/0006-2952(94)00495-8
更新日期：1995-03-01 00:00:00
abstract：:Bcr-abl kinase inhibitors have provided proof of principal that targeted therapy holds great promise for the treatment of cancer. However, despite the success of these agents in treating chronic myelogenous leukemia (CML), the majority of patients continue to present with minimal residual disease contained within the ...
journal_title：Biochemical pharmacology
pub_type： 杂志文章,评审
doi：10.1016/j.bcp.2010.04.003
更新日期：2010-09-01 00:00:00
abstract：:The role of CYP2E1 in ketone-stimulated insulin release was investigated using isolated pancreatic islets of Langerhans and two mammalian insulin secreting pancreatic beta-cell lines engineered to stably express human CYP2E1 (designated BRIN BD11h2E1 and INS-1h2E1). Isolated rat pancreatic islets were shown to express...
journal_title：Biochemical pharmacology
pub_type： 杂志文章
doi：10.1016/j.bcp.2003.10.011
更新日期：2004-03-01 00:00:00
abstract：:Since chlorine placement and the degree of chlorination of the biphenyl nucleus play an important role in the metabolism and ultimate elimination of polychlorinated biphenyls (PCBs), we have studied the metabolism of 4,4'-dichlorobiphenyl (4-DCB) by human hepatic microsomes. This low molecular weight PCB congener is s...
journal_title：Biochemical pharmacology
pub_type： 杂志文章
doi：10.1016/0006-2952(84)90127-8
更新日期：1984-11-01 00:00:00
abstract：:Hepatic microsomal glucuronoconjugation of the hypolipidemic drug clofibric acid was characterized in human liver and compared to the acylglucuronide formation of an endogenous substrate, bilirubin. The affinity of UDP-glucuronosyltransferase for bilirubin was 15-fold higher than for clofibric acid; the Vmax for the t...
journal_title：Biochemical pharmacology
pub_type： 杂志文章
doi：10.1016/0006-2952(87)90459-x
更新日期：1987-11-15 00:00:00
abstract：:The seminal vesicle protein No. 4 (SV-IV) secreted from the rat seminal vesicle epithelium, possesses immunosuppressive and anti-inflammatory properties and it is a potent inhibitor of platelet aggregation both in vivo and in vitro. This research aimed to investigate the possible effect of SV-IV on the process of huma...
journal_title：Biochemical pharmacology
pub_type： 杂志文章
doi：10.1016/0006-2952(94)90106-6
更新日期：1994-07-19 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：:Phospho-tyrosol-indomethacin (PTI; MPI 621), a novel anti-cancer agent, is more potent and safer than conventional indomethacin. Here, we show that PTI was extensively metabolized in vitro and in vivo. PTI was rapidly hydrolyzed by carboxylesterases to generate indomethacin as its major metabolite in the liver microso...
journal_title：Biochemical pharmacology
pub_type： 杂志文章
doi：10.1016/j.bcp.2013.01.031
更新日期：2013-04-15 00:00:00
abstract：:Gram-negative bacilli have become increasingly resistant to antibiotics over the past 2 decades due to selective pressure from the extensive use of antibiotics in the hospital and community. In addition, these bacteria have made optimum use of their innate genetic capabilities to extensively mutate structural and regu...
journal_title：Biochemical pharmacology
pub_type： 杂志文章,评审
doi：10.1016/j.bcp.2005.11.006
更新日期：2006-03-30 00:00:00
abstract：:Histrionicotoxin, a spiropiperidine alkaloid, and twenty-two analogs inhibited binding of [3H]perhydrohistrionicotoxin [( 3H]H12-HTX) and of [3H]phencyclidine [( 3H]PCP) to sites on the acetylcholine receptor-ion complex of Torpedo electroplax membranes. Structural alterations to the nitrogen (secondary amine) or oxyg...
journal_title：Biochemical pharmacology
pub_type： 杂志文章
doi：10.1016/0006-2952(85)90145-5
更新日期：1985-09-01 00:00:00
