Abstract：
:Most of the cytochrome P450 (CYP) genes are expressed in an uneven, zonated pattern in the liver. Factors regulating this regionally restricted expression are not well known. In this study we have analysed cell lysates obtained from opposite zones of rat liver by infusing digitonin to the perfused liver to study the zonation of CYP1A1 and CYP1A2 induction. 3-Methylcholanthrene induced CYP1A1 protein in perivenous cells, while a low dose of beta-naphthoflavone caused periportal induction. Analysis of CYP1A1 mRNA from cell lysates by reverse transcriptase-coupled polymerase chain reaction (RT-PCR) and in situ hybridization experiments both demonstrated that this inducer-specific differently localized effect occurred at the pretranslational level. A corresponding difference in the regional pattern of CYP1A2 induction was seen: induction by beta-naphthoflavone reversed the constitutive perivenous pattern into a periportal CYP1A2 mRNA pattern while induction after 3-methylcholanthrene treatment was more panacinar. Attempts to identify the regiospecific factors involved were made by comparing the in vitro induction of CYP1A1 by beta-naphthoflavone and 3-methylcholanthrene in hepatocytes isolated from the periportal and perivenous region. However, after isolation, induction seemed to be independent of the source of the cells. Our results demonstrate the existence in the liver of regionally acting factors that mediate the induction of CYP1A1 and 1A2 in a local and inducer-specific fashion. These factors could be Ah receptor associated binding proteins operating in vivo, but no longer in isolated cells.
journal_name
Biochem Pharmacoljournal_title
Biochemical pharmacologyauthors
Oinonen T,Saarikoski S,Husgafvel-Pursiainen K,Hirvonen A,Lindros KOdoi
10.1016/0006-2952(94)00385-8subject
Has Abstractpub_date
1994-12-16 00:00:00pages
2189-97issue
12eissn
0006-2952issn
1873-2968pii
0006-2952(94)00385-8journal_volume
48pub_type
杂志文章abstract：:We have reported previously that both dietary iron and selenium regulate intestinal cytochrome P-450 content by modulating the synthesis of its prosthetic heme moiety. Whether these elements are required for synthesis and/or viability of its apocytochrome moiety is unknown. We have examined the effects of intraluminal...
journal_title：Biochemical pharmacology
pub_type： 杂志文章
doi：10.1016/0006-2952(85)90252-7
更新日期：1985-03-01 00:00:00
abstract：:Exposure of lung tissue to Co(II) ions both in vivo and in vitro results in toxicity, a relatively early event of which is the oxidation of cellular glutathione. In this study we have attempted to delineate the relationship between this oxidation of glutathione and the subsequent development of cellular dysfunction. S...
journal_title：Biochemical pharmacology
pub_type： 杂志文章
doi：10.1016/0006-2952(92)90573-2
更新日期：1992-02-04 00:00:00
abstract：:Chlorzoxazone is mainly metabolized to 6-hydroxychloroxazone (6-OHchlorzoxazone) by the ethanol-inducible cytochrome P450 2E1 (CYP2E1). To evaluate the impact of ethanol consumption on the enzyme induction, the pharmacokinetics of chlorozoxazone and 6-OHchlorzoxazone were studied in alcoholic and control subjects. Fif...
journal_title：Biochemical pharmacology
pub_type： 杂志文章
doi：10.1016/0006-2952(94)90524-x
更新日期：1994-04-29 00:00:00
abstract：:Isoliquiritigenin (ILTG) is a flavonoid with chalcone structure (4,2',4'-trihydroxychalcone), an active component present in plants like Glycyrrhiza and Dalbergia which showed various biological activities including anti-inflammatory, anti-carcinogenic and antihistamic. As very little is known in regard to the underly...
journal_title：Biochemical pharmacology
pub_type： 杂志文章
doi：10.1016/j.bcp.2007.01.015
更新日期：2007-05-15 00:00:00
abstract：:DUP 785 (NSC 368390; Brequinar sodium) is a new inhibitor of pyrimidine de novo biosynthesis with antitumor activity against several experimental tumors. DUP 785 inhibits the mitochondrial enzyme dihydroorotate dehydrogenase, blocking the conversion of dihydroorotate to orotate. We examined the influence of exposure t...
journal_title：Biochemical pharmacology
pub_type： 杂志文章
doi：10.1016/0006-2952(88)90636-3
更新日期：1988-09-01 00:00:00
abstract：:Vectorial secretion of cationic compounds across tubular epithelial cells is an important function of the kidney. This uni-directed transport is mediated by two cooperative functions, which are membrane potential-dependent organic cation transporters at the basolateral membranes and H+/organic cation antiporters at th...
journal_title：Biochemical pharmacology
pub_type： 杂志文章,评审
doi：10.1016/j.bcp.2007.12.008
更新日期：2008-05-01 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：:Multidrug resistance (MDR) represents a serious problem in cancer treatment. One strategy to overcome this obstacle is to identify agents that are selectively lethal to MDR cells. The aim of this study was to discover novel compounds against MDR leukemia and to determine the molecular mechanisms behind collateral sens...
journal_title：Biochemical pharmacology
pub_type： 杂志文章
doi：10.1016/j.bcp.2017.10.008
更新日期：2017-12-15 00:00:00
abstract：:Cancer chemoprevention is a new approach in the management of cancer. Traditional cytotoxic chemotherapeutic approaches cannot cure most advanced solid malignancies. Chemoprevention can be defined as the use of non-cytotoxic drugs and natural agents to block the progression to invasive cancer. Recently, isothiocyanate...
journal_title：Biochemical pharmacology
pub_type： 杂志文章
doi：10.1016/j.bcp.2004.03.044
更新日期：2004-09-15 00:00:00
abstract：:Epilepsy is characterised by spontaneous recurrent seizures that are caused by an imbalance between neuronal excitability and inhibition. Since ion channels play fundamental roles in the generation and propagation of action potentials as well as neurotransmitter release at a subset of excitatory and inhibitory synapse...
journal_title：Biochemical pharmacology
pub_type： 杂志文章,评审
doi：10.1016/j.bcp.2020.114043
更新日期：2020-11-01 00:00:00
abstract：:"Ecstasy" [(+/-)-3,4-methylenedioxymethamphetamine or MDMA] is a CNS stimulant, whose use is increasing despite evidence of long-term neurotoxicity. In vitro, the majority of MDMA is demethylenated to (+/-)-3,4-dihydroxymethamphetamine (DHMA) by the polymorphic cytochrome P450 2D6 (CYP2D6). We investigated the demethy...
journal_title：Biochemical pharmacology
pub_type： 杂志文章
doi：10.1016/s0006-2952(02)01028-6
更新日期：2002-06-15 00:00:00
abstract：:We previously demonstrated that the widely used immunosuppressive drugs cyclosporin A (CsA) and tacrolimus (FK506), independent of immunophilin binding, can activate profibrogenic transforming growth factor β (TGFβ)/Smad signaling cascades in rat renal mesangial cells (MC). Here we report that both peptidyl-prolyl cis...
journal_title：Biochemical pharmacology
pub_type： 杂志文章
doi：10.1016/j.bcp.2011.11.001
更新日期：2012-01-15 00:00:00
abstract：:Activation of protein kinase C (PKC) has been suggested to play a role in bone resorption. However, phorbol esters, which activate PKC, have been reported to have both stimulatory and inhibitory effects on bone resorption. To study the role of PKC in bone resorption further, we have measured calcium release elicited b...
journal_title：Biochemical pharmacology
pub_type： 杂志文章
doi：10.1016/s0006-2952(00)00418-4
更新日期：2000-10-01 00:00:00
abstract：:The tumor necrosis factor (TNF) superfamily (TNFSF) includes about thirty structurally related receptors (TNFSFRs) and about twenty protein ligands that bind to one or more of these receptors. Receptors of the tumor necrosis factor (TNF) superfamily (TNFSFRs) are pharmacological targets for treatment of inflammatory a...
journal_title：Biochemical pharmacology
pub_type： 杂志文章
doi：10.1016/j.bcp.2020.114110
更新日期：2020-08-01 00:00:00
abstract：:The kinetics of the reaction of acetaldehyde (AcH) with the alpha-amino group of several di- and tripeptides to form 2-methylimidazolidin-4-one adducts were determined at pH 7, 4, 37 degrees C, using reverse phase HPLC to separate peptides from adducts. The imidazolidin-4-one structure of the adducts was confirmed by ...
journal_title：Biochemical pharmacology
pub_type： 杂志文章
doi：10.1016/0006-2952(95)02408-5
更新日期：1996-05-17 00:00:00
abstract：:The acute effects of carbon tetrachloride (CCl4) on the membrane structure of rat liver microsomes were studied using 31P-NMR and spin-labeling techniques. 31P-NMR spectra of rat liver microsomes were not changed appreciably after the oral administration of CCl4, indicating that the surface structures of microsomal me...
journal_title：Biochemical pharmacology
pub_type： 杂志文章
doi：10.1016/0006-2952(85)90100-5
更新日期：1985-01-01 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：:Studies were performed to investigate the irreversible binding and oxidative metabolism of propranolol in human liver microsomes and the relationship of binding and metabolism to the polymorphic oxidation of debrisoquine. Incubation of microsomes with 14C-labelled propranolol in the presence of a NADPH-generating syst...
journal_title：Biochemical pharmacology
pub_type： 杂志文章
doi：10.1016/0006-2952(87)90592-2
更新日期：1987-07-15 00:00:00
abstract：:The inhibition of formyl-methionyl-leucyl-phenylalanine (fMLP)-induced superoxide anion (O2(.-)) generation by 2-benzyloxybenzaldehyde (CCY1a) was investigated in rat neutrophils, and the underlying mechanism of this inhibition was assessed. CCY1a concentration-dependently inhibited O2(.-) generation (IC(50)=18.5+/-4....
journal_title：Biochemical pharmacology
pub_type： 杂志文章
doi：10.1016/s0006-2952(03)00006-6
更新日期：2003-04-01 00:00:00
abstract：:Two specific binding sites for histamine were characterized in the cell membrane of N-nitroso-N-methylurea (NMU)-induced tumors. The first one, with higher affinity (Kd = 4 +/- 2 nM), was further identified as an H2 type, while the lower affinity one (35 +/- 10 nM) corresponded to an H1 receptor. Histamine concentrati...
journal_title：Biochemical pharmacology
pub_type： 杂志文章
doi：10.1016/0006-2952(95)00108-c
更新日期：1995-06-29 00:00:00
abstract：:The effect of exhaustive exercise on the hepatobiliary transport of organic anions was investigated in rats. Animals were run on a rodent treadmill at 24 m/min up a 12% grade (152 +/- 15 min). Exercise resulted in significant hypoglycaemia (-46%) and increased plasma levels of lactate (+12%), together with a marked re...
journal_title：Biochemical pharmacology
pub_type： 杂志文章
doi：10.1016/0006-2952(90)90094-2
更新日期：1990-12-01 00:00:00
abstract：:Chronic administration of the beta-adrenergic receptor agonist isoproterenol (5 mg/200 g animal for 10 days) resulted in rat parotid and submandibular gland hypertrophy, and it induced synthesis of a series of proline-rich proteins (PRPs) and glycoproteins. Treated parotid glands additionally exhibit an increase in ac...
journal_title：Biochemical pharmacology
pub_type： 杂志文章
doi：10.1016/0006-2952(85)90277-1
更新日期：1985-12-15 00:00:00
abstract：:The addition of atrial natriuretic peptide (ANP) to isolated human adipocytes in primary culture from very obese individuals resulted in an inhibition of leptin release after a 24- or 48-hr incubation. There was also an inhibition of leptin release by isoproterenol (ISO) that was partially reversed by insulin, whereas...
journal_title：Biochemical pharmacology
pub_type： 杂志文章
doi：10.1016/s0006-2952(03)00154-0
更新日期：2003-06-01 00:00:00
abstract：:The effects of muscimol, aminooxyacetic acid (AOAA), diamino-n-butyric acid (DABA), baclofen, bicuculline, picrotoxin, strychnine, diazepam, phenobarbitone and phenytoin on cimetidine-induced seizures were studied in mice. Cimetidine (400-1000 mg/kg, i.p.) induced dose-dependent tonic convulsion. Muscimol, AOAA and DA...
journal_title：Biochemical pharmacology
pub_type： 杂志文章
doi：10.1016/0006-2952(93)90606-w
更新日期：1993-12-14 00:00:00
abstract：:We have previously shown [8] that rat liver adenosine kinase can produce [14C]AMP from [14C]adenosine (Ado) and unlabelled adenosine monophosphate (AMP), in the absence of ATP, by an exchange reaction. In this study, we investigated whether Ado or AMP could be replaced in this exchange reaction by other nucleosides or...
journal_title：Biochemical pharmacology
pub_type： 杂志文章
doi：10.1016/0006-2952(95)02033-0
更新日期：1995-11-09 00:00:00
abstract：:Carvedilol, a non-selective beta-adrenoreceptor blocker, has been shown to possess a high degree of cardioprotection in experimental models of myocardial damage. Reactive oxygen species have been proposed to be implicated in such situations, and antioxidants have been demonstrated to provide partial protection to the ...
journal_title：Biochemical pharmacology
pub_type： 杂志文章
doi：10.1016/s0006-2952(00)00522-0
更新日期：2001-01-15 00:00:00
abstract：:Vindesine biotransformation was investigated using a bank of human liver microsomes. The drug was converted into one major metabolite (M) upon incubation with the microsomes. Large interindividual variations were observed: vindesine biotransformation rates ranged from 1.2 to 12.9 pmol/min/mg protein. Vindesine metabol...
journal_title：Biochemical pharmacology
pub_type： 杂志文章
doi：10.1016/0006-2952(93)90169-w
更新日期：1993-02-24 00:00:00
abstract：:It has been reported that endothelins (ETs) stimulate catecholamine release from chromaffin cells. However, it is not known whether ETs also affect catecholamine biosynthesis. Thus, using a rat pheochromocytoma cell line, PC12, we examined the effects of ETs on catecholamine biosynthesis. The mRNA level and activity o...
journal_title：Biochemical pharmacology
pub_type： 杂志文章
doi：10.1016/s0006-2952(01)00862-0
更新日期：2002-03-01 00:00:00
abstract：:5-Substituted-2,2'-anhydrouridines are a new class of competitive inhibitors of uridine phosphorylase. The most potent member of the series is 2,2'-anhydro-5-ethyluridine with an apparent Ki value of 25 nM. These compounds are selective inhibitors of uridine phosphorylase and have no effect on thymidine phosphorylase....
journal_title：Biochemical pharmacology
pub_type： 杂志文章
doi：10.1016/0006-2952(85)90643-4
更新日期：1985-05-15 00:00:00
abstract：:Female Wistar rats were treated with acetaminophen 3.0 g/kg BW and allyl alcohol 75 microliter/kg BW by gastric tube. Hepatic function, measured as galactose elimination capacity and prothrombin index, was reduced to about 0.40 times control value. Plasma alanine transferase activity was elevated more and earlier afte...
journal_title：Biochemical pharmacology
pub_type： 杂志文章
doi：10.1016/0006-2952(85)90750-6
更新日期：1985-03-15 00:00:00
