Abstract：
:The genetically controlled polymorphic oxidation of debrisoquine and sparteine is caused by the absence or functional deficiency of a cytochrome P-450 isozyme. In order to elucidate the mechanisms underlying the differences in cytochrome P-450 function we have studied the 1'-hydroxylation of the prototype drug bufuralol in human liver microsomes of individuals phenotyped in vivo as extensive metabolizers (EM, N = 10), poor metabolizers (PM, N = 5) and in subjects with an intermediate rate of metabolism (IM, N = 4). PM- as compared to EM-microsomes were characterized by a decreased Vmax for (+)-bufuralol 1'-hydroxylation (7.51 +/- 2.03 nmol X mg-1 X hr-1 vs 11.95 +/- 4.80 nmol X mg-1 X hr-1) but not for (-)-bufuralol 1'-hydroxylation (4.72 +/- 0.87 nmol X mg-1 X hr-1 vs 5.55 +/- 1.49 nmol X mg-1 X hr-1). The apparent Km for (+)-bufuralol 1'-hydroxylation was increased in PM microsomes (118 +/- 84.9 microM vs 17.9 +/- 6.30 microM). Inhibition of bufuralol 1'-hydroxylation by quinidine was biphasic in EM microsomes, providing further support for the involvement of at least two cytochrome P-450 isozymes. Quinidine acted as a competitive inhibitor of only the high affinity/stereoselectivity component of the reaction. Our data suggest that the debrisoquine/sparteine type of oxidation polymorphism is caused by an almost complete loss of a minor cytochrome P-450 isozyme which has a high affinity and stereoselectivity for (+)-bufuralol and a high sensitivity to inhibition by quinidine.
journal_name
Biochem Pharmacoljournal_title
Biochemical pharmacologyauthors
Dayer P,Kronbach T,Eichelbaum M,Meyer UAdoi
10.1016/0006-2952(87)90573-9subject
Has Abstractpub_date
1987-12-01 00:00:00pages
4145-52issue
23eissn
0006-2952issn
1873-2968pii
0006-2952(87)90573-9journal_volume
36pub_type
杂志文章abstract：:It was shown previously that three 1,5-diazabicyclo[3.1.0]hexane-2,4-diones selectively inhibited human Type II IMP dehydrogenase (IMPDH) from Tmolt4 cell leukemia [Barnes et al., Biochemistry 2000;39:13641-50]. The agents acted as competitive inhibitors of this isoform, yet when tested against human Type I at concent...
journal_title：Biochemical pharmacology
pub_type： 杂志文章
doi：10.1016/s0006-2952(01)00649-9
更新日期：2001-07-01 00:00:00
abstract：:Tannic acid (TA) is a naturally occurring phenol, which has been found to display an antipromotion effect on mouse skin carcinogenesis. In order to explore the molecular mechanism, we have examined the process of 12-O-tetradecanoylphorbol-13-acetate (TPA)-induced protein kinase C (PKC) activation, including phorbol es...
journal_title：Biochemical pharmacology
pub_type： 杂志文章
doi：10.1016/0006-2952(93)90095-e
更新日期：1993-10-19 00:00:00
abstract：:The 5-HT1A receptor is a critical mediator of serotonergic (5-HT) function. We have identified 13 potential single nucleotide polymorphisms resulting in amino acid changes throughout the human 5-HT1A receptor. The pharmacological profiles of these 13 polymorphic variants were then characterized using a high-throughput...
journal_title：Biochemical pharmacology
pub_type： 杂志文章
doi：10.1016/j.bcp.2003.09.030
更新日期：2004-02-01 00:00:00
abstract：:Accumulation of radioactive iron (59Fe) into isolated fragments of rat small intestine in the presence of two hydroxypyrones, maltol and ethyl maltol, was compared with that in the presence of another chelator of iron(III), nitrilotriacetic acid (NTA). The characteristics of uptake were similar with all three ligands....
journal_title：Biochemical pharmacology
pub_type： 杂志文章
doi：10.1016/0006-2952(88)90556-4
更新日期：1988-05-15 00:00:00
abstract：:Vanadate (VO3-) was found to activate adenylyl cyclase (AC) in ocular ciliary process membrane. This response was additive to that of isoproterenol (ISO) and vasoactive intestinal peptide (VIP), but it was potentiative with forskolin (FSK) and also with Ca2+/calmodulin activation of AC activity. The potentiated respon...
journal_title：Biochemical pharmacology
pub_type： 杂志文章
doi：10.1016/0006-2952(93)90284-4
更新日期：1993-03-24 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：: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：:In an effort to identify the human cytochromes P450 involved in the N-demethylation of dextromethorphan, the kinetics of 3-methoxymorphinan formation were studied in microsomal enzyme systems. Under initial rate conditions, 3-methoxymorphinan formation demonstrated single enzyme Michaelis-Menten kinetics using microso...
journal_title：Biochemical pharmacology
pub_type： 杂志文章
doi：10.1016/0006-2952(94)90237-2
更新日期：1994-07-05 00:00:00
abstract：:Pain is a classical sign of inflammation, and sensitization of primary sensory neurons (PSN) is the most important mediating mechanism. This mechanism involves direct action of inflammatory mediators such as prostaglandins and sympathetic amines. Pharmacologic control of inflammatory pain is based on two principal str...
journal_title：Biochemical pharmacology
pub_type： 杂志文章,评审
doi：10.1016/j.bcp.2020.113862
更新日期：2020-06-01 00:00:00
abstract：:The use of either methadone or buprenorphine for treatment of the pregnant opiate-dependent patient improves maternal and neonatal outcome. However, patient outcomes are often complicated by neonatal abstinence syndrome (NAS). The incidence and severity of NAS should depend on opiate concentration in the fetal circula...
journal_title：Biochemical pharmacology
pub_type： 杂志文章
doi：10.1016/j.bcp.2009.07.002
更新日期：2009-11-01 00:00:00
abstract：:The effect of the anti-tumor, anti-glutamine drug acivicin, L-(alpha S,5S)-alpha-amino-3-chloro-4,5-dihydro-5-isoxazoleacetic acid, was determined on the activity of the rate-limiting enzyme of de novo pyrimidine biosynthesis, carbamoyl-phosphate synthetase II (glutamine-hydrolyzing) (EC 6.3.5.5), in human colon carci...
journal_title：Biochemical pharmacology
pub_type： 杂志文章
doi：10.1016/0006-2952(85)90106-6
更新日期：1985-01-01 00:00:00
abstract：:Mechanical stress is known to activate signaling cascades, including mitogen-activated protein kinase (MAPK) pathways. Although mechanical stress has been implicated in hepatic cirrhosis and liver regeneration following hepatectomy, the signaling pathway(s) that may be activated in hepatocytes in response to mechanica...
journal_title：Biochemical pharmacology
pub_type： 杂志文章
doi：10.1016/j.bcp.2005.07.019
更新日期：2005-12-05 00:00:00
abstract：:Phosphatidylinositol specific phospholipase C from Staphylococcus aureus could solubilize acetylcholinesterase up to 55% from sheep platelets in the presence of ethylenediaminetetra acetic acid (EDTA). The endogenous phosphatidylinositol specific phospholipase C of platelets activated by deoxycholate (at 3-5 mM) could...
journal_title：Biochemical pharmacology
pub_type： 杂志文章
doi：10.1016/0006-2952(85)90202-3
更新日期：1985-12-01 00:00:00
abstract：:Cholesterol 7 alpha-hydroxylase (CH-7 alpha) activity in HepG2 cells depleted of glutathione (GSH) was reduced significantly (P < 0.05) compared to that in untreated controls. Northern blot analysis of poly A+ mRNA isolated from GSH-depleted and control HepG2 cells showed that there was a reduction in mRNA for CH-7 al...
journal_title：Biochemical pharmacology
pub_type： 杂志文章
doi：10.1016/0006-2952(92)90553-u
更新日期：1992-10-06 00:00:00
abstract：:Recently, we reported that alterations in topoisomerase II (topo II) activity appear to contribute to mitomycin C (MMC) resistance in HT-29R13 human colon cancer cells under aerobic conditions. In this study, the expression of topo II alpha and topo II beta in parent HT-29 and MMC resistant variant HT-29R13 cells was ...
journal_title：Biochemical pharmacology
pub_type： 杂志文章
doi：10.1016/0006-2952(96)00343-7
更新日期：1996-08-23 00:00:00
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 w...
journal_title：Biochemical pharmacology
pub_type： 杂志文章
doi：10.1016/0006-2952(93)90219-m
更新日期：1993-06-22 00:00:00
abstract：:Carbon tetrachloride (CCl4)-induced inhibition of very low density lipoprotein (VLDL) secretion was studied in isolated hepatocytes. The hypothesis that inhibition of secretion is due to altered calcium homeostasis following CCl4-dependent inhibition of endoplasmic reticulum calcium sequestration was investigated. Inh...
journal_title：Biochemical pharmacology
pub_type： 杂志文章
doi：10.1016/0006-2952(84)90714-7
更新日期：1984-08-01 00:00:00
abstract：:Rats were killed after 6 weeks of continuous ingestion of the pneumotoxic alkaloid monocrotaline (2.2 mg/kg/day), the neutrophil elastase inhibitor SC39026 (60 mg/kg/day), or both. Pulmonary reactions were evaluated by light and electron microscopy. Lung endothelial function was monitored by angiotensin converting enz...
journal_title：Biochemical pharmacology
pub_type： 杂志文章
doi：10.1016/0006-2952(89)90084-1
更新日期：1989-08-01 00:00:00
abstract：:Hyperglycaemia increases the generation of reactive oxidants in blood vessels and is a major cause of endothelial dysfunction. A water-soluble selenium-containing sugar (1,4-Anhydro-4-seleno-d-talitol, SeTal) has potent antioxidant activity in vitro and is a promising treatment to accelerate wound healing in diabetic ...
journal_title：Biochemical pharmacology
pub_type： 杂志文章
doi：10.1016/j.bcp.2016.12.019
更新日期：2017-03-15 00:00:00
abstract：:Emodin (1,3,8-trihydroxy-6-methylanthraquinone) is an active constituent of Rheum palmatum, and showed inhibitory activity on lipopolysaccharide-induced NO production in our previous study. However, the apoptosis-inducing activity of emodin has remained undefined. Among three structurally related anthraquinones, inclu...
journal_title：Biochemical pharmacology
pub_type： 杂志文章
doi：10.1016/s0006-2952(02)01386-2
更新日期：2002-12-15 00:00:00
abstract：:Bromodomains are epigenetic readers of histone acetylation involved in chromatin remodeling and transcriptional regulation. The human proteome comprises 46 bromodomain-containing proteins with a total of 61 bromodomains, which, despite highly conserved structural features, recognize a wide array of natural peptide lig...
journal_title：Biochemical pharmacology
pub_type： 杂志文章,评审
doi：10.1016/j.bcp.2015.12.005
更新日期：2016-04-15 00:00:00
abstract：:The aim of this study was to find the peptide ligands to inhibit Candida albicans secreted aspartyl proteinase 2 (Sap2). First, a ligand library, containing 300 different peptides, was constructed, and their interaction with Sap2 was separately calculated by molecular dynamic software. Second, 10 peptide ligands with ...
journal_title：Biochemical pharmacology
pub_type： 杂志文章
doi：10.1016/j.bcp.2014.05.020
更新日期：2014-08-15 00:00:00
abstract：:Heme oxygenase 1 (HO-1) is a stress protein and has been suggested to provide defense mechanisms against agents that may induce oxidative injury. Vitamin E (VE) is considered to function as an important cellular antioxidant. Rats were fed a VE-deficient (0E) or a VE-sufficient (10E) diet for 6 weeks and then were intr...
journal_title：Biochemical pharmacology
pub_type： 杂志文章
doi：10.1016/s0006-2952(97)00302-x
更新日期：1997-11-15 00:00:00
abstract：:Cobalt is suspected to cause memory deficit in humans and was reported to induce neurotoxicity in animal models. We have studied the effects of cobalt in primary cultures of mouse astrocytes. CoCl(2) (0.2-0.8mM) caused dose-dependent ATP depletion, apoptosis (cell shrinkage, phosphatidylserine externalization and chro...
journal_title：Biochemical pharmacology
pub_type： 杂志文章
doi：10.1016/j.bcp.2006.11.008
更新日期：2007-03-01 00:00:00
abstract：:Diabetic retinopathy is one of the leading causes of blindness and the most common complication of diabetes with no cure available. We investigated the role of phospholipases A2 (PLA2) in diabetic retinopathy using an in vitro blood-retinal barrier model (BRB) and an in vivo streptozotocin (STZ)-induced diabetic model...
journal_title：Biochemical pharmacology
pub_type： 杂志文章
doi：10.1016/j.bcp.2013.09.008
更新日期：2013-12-01 00:00:00
abstract：:Pyruvate is an important metabolic intermediate, and also is an effective scavenger of hydrogen peroxide and other reactive oxygen species (ROS). Pharmacological administration of pyruvate has been shown to improve organ function in animal models of oxidant-mediated cellular injury. However, pyruvate is relatively uns...
journal_title：Biochemical pharmacology
pub_type： 杂志文章,评审
doi：10.1016/j.bcp.2010.03.007
更新日期：2010-07-15 00:00:00
abstract：:We have examined, relative to clofibric acid (CPIB), the effects of a chemical series of phenoxyacetic acids and of two asymmetric CPIB analogues, the R(+)- and S(-)-enantiomers of 2-(4-chlorophenoxy)propionic acid (4-CPPA) and 2-(4-chlorophenoxy)butyric acid (4-CPBA), on hepatic peroxisome proliferation both in vivo ...
journal_title：Biochemical pharmacology
pub_type： 杂志文章
doi：10.1016/0006-2952(90)90392-x
更新日期：1990-09-15 00:00:00
abstract：:A series of isoquinolines, N-methyl-1,2-dihydroisoquinolines, N-methyl-1,2,3,4-tetrahydroisoquinolines, 1,2,3,4-tetrahydroisoquinolines, and N-methylisoquinolinium ions were tested as inhibitors of monoamine oxidases A and B. All compounds were found to act as reversible and time-independent MAO inhibitors, often with...
journal_title：Biochemical pharmacology
pub_type： 杂志文章
doi：10.1016/0006-2952(95)00220-t
更新日期：1995-09-07 00:00:00
abstract：:The binding of nimodipine, a 1,4-dihydropyridine Ca2+ channel antagonist, and of Bay K 8644, a Ca2+ channel activator, was measured in several regions of rat brain and compared to the distribution of K+ depolarization-induced 45Ca2+ uptake into synaptosomes. The maximum binding densities (Bmax) of [3H]nimodipine and [...
journal_title：Biochemical pharmacology
pub_type： 杂志文章
doi：10.1016/0006-2952(87)90575-2
更新日期：1987-12-01 00:00:00
abstract：:Purification of functional nucleoside transporters has been hampered by the instability of detergent-solubilized proteins. The present study was undertaken to determine if the presence of specific transporter ligands in the solubilization medium could enhance the functional stability of the isolated proteins. Ehrlich ...
journal_title：Biochemical pharmacology
pub_type： 杂志文章
doi：10.1016/s0006-2952(96)00857-x
更新日期：1997-03-07 00:00:00
