Abstract:
:Experiments were conducted to determine how selective inhibitors of certain cyclic nucleotide phosphodiesterase (PDE) families, namely CI-930 (PDE3 inhibitor; 3-(2H)-pyridazinone-4,5-dihydro-6-[4-(1H-imidazolyl) phenyl]-5-methyl monohydro chloride) and rolipram (PDE4 inhibitor), may affect human coronary artery smooth muscle cell (HCASMC) proliferation. CI-930- and rolipram-inhibitable PDEs accounted for most of the cyclic AMP hydrolyzing activity in HCASMC. Twenty micromolar CI-930 and 20 microM rolipram used individually attenuated proliferation of HCASMC from some, but not all donors, as measured by flow cytometry. The simultaneous addition of 10 microM CI-930 plus 10 microM rolipram caused greater attenuation. This attenuation represented a reduction of the number of cells entering the S phase of the cell cycle and not merely a delay in cell cycle traverse. No statistically significant elevation of cyclic AMP was detected following the addition of either PDE inhibitor individually, but the combination produced significant elevations. It is concluded that CI-930- and rolipram-inhibitable PDE isozymes are expressed in HCASMC and that selective inhibitors of these isozymes can attenuate HCASMC proliferation. The data suggest that selective PDE inhibitors may prevent restenosis in patients following percutaneous transluminal coronary angioplasty because of their effect on HCASMC proliferation, and they may also be useful in retarding the progression of atherosclerosis in individuals at risk. PDE3 and PDE4 inhibitors in combination are more effective than the inhibitors used individually.
journal_name
Biochem Pharmacoljournal_title
Biochemical pharmacologyauthors
Johnson-Mills K,Arauz E,Coffey RG,Krzanowski JJ Jr,Polson JBdoi
10.1016/s0006-2952(98)00239-1subject
Has Abstractpub_date
1998-10-15 00:00:00pages
1065-73issue
8eissn
0006-2952issn
1873-2968pii
S0006295298002391journal_volume
56pub_type
杂志文章abstract::Alone and in synergistic combination with retinoids, dietary glucarate inhibits both the chemical induction and growth of rat mammary tumors. To investigate the pharmacokinetics of glucarate, [14C]glucarate was synthesized, converted to the calcium salt, and administered to rats bearing primary mammary tumors. When gi...
journal_title:Biochemical pharmacology
pub_type: 杂志文章
doi:10.1016/0006-2952(94)90544-4
更新日期:1994-04-29 00:00:00
abstract::A method is presented that determines the degree of attachment of cancer cells to normal cells. This method may be useful in determining the extent to which treatment of normal cells (or of a tumor-bearing host) with a particular chemotherapeutic agent may affect the degree of attachment of cancer cells to the normal ...
journal_title:Biochemical pharmacology
pub_type: 杂志文章
doi:10.1016/0006-2952(85)90405-8
更新日期:1985-06-15 00:00:00
abstract::Lesions to DNA trigger the DNA-damage response (DDR), a complex, multi-branched cell-intrinsic process targeted to DNA repair, or elimination of the damaged cells by apoptosis. DDR aims at reducing permanence of mutated cells, decreasing the risk of tumor development: the more stringent the response, the lower the lik...
journal_title:Biochemical pharmacology
pub_type: 杂志文章,评审
doi:10.1016/j.bcp.2012.07.022
更新日期:2012-11-15 00:00:00
abstract::Regional adrenergic function is difficult to assess in humans. Tyramine given through a microdialysis probe may be a useful tool in this regard. However, tyramine data is hard to interpret given the drug's complex mode of action. We characterized the response to tyramine, isoproterenol, and dopamine in adipose tissue ...
journal_title:Biochemical pharmacology
pub_type: 杂志文章
doi:10.1016/j.bcp.2006.09.004
更新日期:2006-12-15 00:00:00
abstract::The formation of 4-[1,4-13C]hydroxybutyric acid ([13C]gamma-hydroxybutyric acid; [13C]GHB) in rat brain was studied following intracerebroventricular (i.c.v.) administration of either 4-[1,4-13C]aminobutyric acid ([13C]GABA or 1,4-[1,4-13C]butanediol ([13C]1,4-BD) to awake, freely moving animals. GHB and [13C]GHB were...
journal_title:Biochemical pharmacology
pub_type: 杂志文章
doi:10.1016/0006-2952(89)90645-x
更新日期:1989-12-15 00:00:00
abstract::Diabetic retinopathy (DR) is the most frequent complication of diabetes and one of leading causes of blindness worldwide. Early phases of DR are characterized by retinal pericyte loss mainly related to concurrent inflammatory process. Recently, an important link between P2X7 receptor (P2X7R) and inflammation has been ...
journal_title:Biochemical pharmacology
pub_type: 杂志文章
doi:10.1016/j.bcp.2017.05.001
更新日期:2017-08-15 00:00:00
abstract::Thromboxane A2 is a potent mediator of inflammation and platelet aggregation exerting its effects through the activation of a G protein-coupled receptor (GPCR), termed TP. Although the existence of dimers/oligomers in Class A GPCRs is widely accepted, their functional significance still remains controversial. Recently...
journal_title:Biochemical pharmacology
pub_type: 杂志文章
doi:10.1016/j.bcp.2016.11.010
更新日期:2017-01-15 00:00:00
abstract::Stress, be it from environmental factors or intrinsic to the cell as result of growth and metabolism, can be harmful to cells. Mammalian cells have developed numerous mechanisms to respond to diverse forms of stress. These mechanisms combine signaling cascades and activation of gene expression programs to orchestrate ...
journal_title:Biochemical pharmacology
pub_type: 杂志文章,评审
doi:10.1016/j.bcp.2006.07.002
更新日期:2006-11-30 00:00:00
abstract::Induction of the breast cancer resistance protein (BCRP/ABCG2) expression has been found in various tissues and cell-types after exposure to chemicals including 17β-estradiol, rosiglitazone, imatinib, as well as aryl hydrocarbon receptor (AhR) activators such as 2,3,7,8-tetrachlorodibenzodioxin, 3-methylcholanthrene (...
journal_title:Biochemical pharmacology
pub_type: 杂志文章
doi:10.1016/j.bcp.2010.08.016
更新日期:2010-12-01 00:00:00
abstract::Rational approaches to targeted cancer therapy have begun to predominate the pipelines of oncology drug development. Our rapidly increasing understanding of the "wiring" of tumor cells and the vulnerabilities of such cells that can potentially be exploited through targeted treatments has opened up enormous opportuniti...
journal_title:Biochemical pharmacology
pub_type: 杂志文章,评审
doi:10.1016/j.bcp.2010.03.001
更新日期:2010-09-01 00:00:00
abstract::In artificially ventilated beagle dogs a severe hypoglycemic condition was induced by insulin injection, while the posthypoglycemic recovery was induced by glucose treatment at the end of a 20-min period of spontaneous electroencephalographic silence. The motor area of the cerebral cortex was analyzed for glycolytic m...
journal_title:Biochemical pharmacology
pub_type: 杂志文章
doi:10.1016/0006-2952(83)90629-9
更新日期:1983-03-15 00:00:00
abstract::Auranofin (AF) is a newly introduced oral gold compound having antirheumatic properties, and its efficacy in the treatment of bronchial asthma is now under investigation. In this study, we examined the effects of AF on leukotriene (LT) formation by human polymorphonuclear leukocytes (PMNs) stimulated with the calcium ...
journal_title:Biochemical pharmacology
pub_type: 杂志文章
doi:10.1016/0006-2952(87)90113-4
更新日期:1987-05-01 00:00:00
abstract::CCl4 induced cellular injury and its modification by prostacyclin (PGI2) was studied in cultured rat hepatocytes. Biosynthesis of both intracellular and serum proteins and that of phospholipids decreased upon CCl4 treatments (IC50 7.0, 2.5 and 3.2 mM, respectively). After 1 hr exposure of the cells to CCl4, the reduct...
journal_title:Biochemical pharmacology
pub_type: 杂志文章
doi:10.1016/0006-2952(90)90443-o
更新日期:1990-10-01 00:00:00
abstract::Interleukin-2 (IL-2) has been shown to decrease cytochrome P450 (CYP) mRNAs and proteins in cultured rat hepatocytes, and IL-2 administration decreases CYPs in rats. Although high doses of IL-2 are administered to cancer patients, the effect on human CYPs has not yet been determined. Patients with hepatic metastases f...
journal_title:Biochemical pharmacology
pub_type: 临床试验,杂志文章,随机对照试验
doi:10.1016/s0006-2952(98)00372-4
更新日期:1999-04-15 00:00:00
abstract::Irradiation of a cytosolic fraction from vascular smooth muscle in the presence of [3H]felodipine resulted in the labelling of a protein with an apparent molecular weight of 62 kDa. The labelling was seen on UV-irradiation at 360 nm, but not at 254, 278 or at wavelengths above 410 nm. The photolabelling was enhanced i...
journal_title:Biochemical pharmacology
pub_type: 杂志文章
doi:10.1016/0006-2952(89)90516-9
更新日期:1989-12-01 00:00:00
abstract::Phenylbutyrate has been shown recently to induce fetal hemoglobin (HbF) production in patients with sickle cell anemia and beta thalassemia. We have now examined related aromatic fatty acids in order to define the range of active structures and identify plausible mechanisms of action. Structure-function analysis revea...
journal_title:Biochemical pharmacology
pub_type: 杂志文章
doi:10.1016/0006-2952(96)00476-5
更新日期:1996-10-25 00:00:00
abstract::The effects of cetaben and clofibric acid were compared on the activities of peroxisomal enzymes in the liver and kidney of male Wistar rats. Cetaben at 200 mg/kg body wt increased the activities of all of the enzymes in the liver that were studied two to eight times, whereas the changes induced by the same dose of cl...
journal_title:Biochemical pharmacology
pub_type: 杂志文章
doi:10.1016/0006-2952(94)90183-x
更新日期:1994-02-09 00:00:00
abstract::In this study we examined the metabolism of hypoxanthine in fibroblast growth factor (FGF)-stimulated porcine aortic endothelial cells (PAEC). Our previous report indicated that hypoxanthine in fetal bovine serum (FBS) was an essential component for both basal and FGF-dependent growth of PAEC (Hayashi et al., Exp Cell...
journal_title:Biochemical pharmacology
pub_type: 杂志文章
doi:10.1016/0006-2952(93)90311-j
更新日期:1993-04-22 00:00:00
abstract::The formyl peptide receptor (FPR) gene family has a complex evolutionary history and comprises eight murine members but only three human representatives. To enable translation of results obtained in mouse models of human diseases, more comprehensive knowledge of the pharmacological similarities/differences between the...
journal_title:Biochemical pharmacology
pub_type: 杂志文章
doi:10.1016/j.bcp.2016.09.004
更新日期:2016-11-01 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::The mammalian thioredoxin reductase (TrxR) isoenzymes, TrxR1 in cytosol or nucleus, TrxR2 in mitochondria, and TrxR3 in testis, are essential seleno-flavoenzymes with a conserved penultimate selenocysteine (Sec) residue at the C-terminus, and have attracted increasing interests as potential targets for development of ...
journal_title:Biochemical pharmacology
pub_type: 杂志文章
doi:10.1016/j.bcp.2015.12.004
更新日期:2016-02-15 00:00:00
abstract::Pregnancy is associated with uteroplacental and vascular remodeling in order to adapt for the growing fetus and the hemodynamic changes in the maternal circulation. We have previously shown upregulation of uterine matrix metalloproteinases (MMPs) during pregnancy. Whether pregnancy-associated changes in MMPs are local...
journal_title:Biochemical pharmacology
pub_type: 杂志文章
doi:10.1016/j.bcp.2013.06.030
更新日期:2013-09-15 00:00:00
abstract::Hepatic expression of multiple cytochrome P450 genes is suppressed in the livers of rats undergoing an inflammatory response. Nitric oxide (NO) released during inflammation has been implicated in the decreased activities and expression of several cytochrome P450 isozymes. We examined the role of cytokine-mediated NO r...
journal_title:Biochemical pharmacology
pub_type: 杂志文章
doi:10.1016/s0006-2952(97)00226-8
更新日期:1997-09-15 00:00:00
abstract::The maintenance of the characteristic lipid compositions and physicochemical properties of biological membranes is essential for their proper function. Mechanisms allowing to sense and restore membrane homeostasis have been identified in prokaryotes for a long time and more recently in eukaryotes. A membrane remodelin...
journal_title:Biochemical pharmacology
pub_type: 杂志文章,评审
doi:10.1016/j.bcp.2018.02.022
更新日期:2018-07-01 00:00:00
abstract::The disposition and metabolic fate of benzylpenicillin conjugated to a protein, human serum albumin (HSA), were compared with those of free penicillin in the rat. The conjugate was prepared by in vitro incubation of [3H]-benzylpenicillin and HSA at pH 10.8 for 24 hr at 37 degrees, conditions which favour the formation...
journal_title:Biochemical pharmacology
pub_type: 杂志文章
doi:10.1016/0006-2952(87)90314-5
更新日期:1987-10-15 00:00:00
abstract::The ability of the fetus to detoxify transplacental drugs and chemicals can be a critical determinant of teratogenesis and developmental toxicity. Developmentally regulated expression of alpha class glutathione S-transferases (GSTs) is of particular interest, since these isozymes have high activity toward peroxidative...
journal_title:Biochemical pharmacology
pub_type: 杂志文章
doi:10.1016/s0006-2952(02)01017-1
更新日期:2002-06-01 00:00:00
abstract::To assess the relative contributions that the sodium channel blocking activity of propranolol may play in a variety of its therapeutic applications, its effects were examined in vitro with a sodium channel specific 22Na+ uptake system, using rat brain membranes. Propranolol inhibited 22Na+ uptake in the rat brain memb...
journal_title:Biochemical pharmacology
pub_type: 杂志文章
doi:10.1016/0006-2952(82)90668-2
更新日期:1982-05-01 00:00:00
abstract::Superoxide radicals have been implicated in the pathogenesis of aging, cataract, ischemia-reperfusion, cancer and inflammatory diseases. In the present work, we found that deferiprone (L1), an iron-chelating drug, and dietary dihydroxycinnamic acids (catechols) were much more effective at protecting isolated rat hepat...
journal_title:Biochemical pharmacology
pub_type: 杂志文章
doi:10.1016/s0006-2952(01)00821-8
更新日期:2001-12-15 00:00:00
abstract::The anti-peroxidative activity of eugenol on Fe(2+)-ascorbate- and Fe(2+)-H2O2-induced lipid peroxidation was studied using rat liver mitochondria. Eugenol inhibited thiobarbituric acid reactive substance (TBARS) formation induced by both the systems in addition to oxygen uptake and mitochondrial swelling induced by F...
journal_title:Biochemical pharmacology
pub_type: 杂志文章
doi:10.1016/0006-2952(92)90318-d
更新日期:1992-06-09 00:00:00
abstract::The mechanism by which p-chlorophenoxyisobutyric acid (clofibric acid) induces striking changes in the proportion of the molecular species of phosphatidylcholine (PC) in rat liver was studied. Treatment of rats with clofibric acid strikingly increased the content of 1-palmitoyl-2-oleoyl (16:0-18:1) PC, but decreased t...
journal_title:Biochemical pharmacology
pub_type: 杂志文章
doi:10.1016/s0006-2952(01)00735-3
更新日期:2001-10-01 00:00:00