Abstract:
:A 1.57kb BamH1 fragment containing a full-length human debrisoquine 4-hydroxylase cytochrome P450 (CYP2D6) cDNA was inserted into the BglII site of the yeast expression plasmid pMA91 and the resulting recombinant plasmid, PELT1, introduced into Saccharomyces cerevisiae strain AH22. Microsomes prepared from AH22/pELT1 cells gave an absorption maximum at 448 nm and a P450 content of 67 +/- 31 pmol/mg of microsomal protein. No P450 was detectable in microsomes prepared from AH22/pMA91 control cells. A western blot of microsomes prepared from yeast transformed with pELT1 were probed with a monoclonal antibody to CYP2D6 and revealed a strong band with a molecular mass consistent with that of CYP2D6 from human liver microsomes. No corresponding band was observed with microsomes from control yeast transformed with pMA91 alone. Microsomes from AH22/pELT cells showed catalytic activity towards metoprolol (alpha-hydroxylation and O-demethylation, 0.17 and 0.78 nmol/mg protein/h, respectively); and towards sparteine (2- and 5-dehydrogenation, 1.82 and 0.59 nmol/mg protein/h, respectively). The inhibition of metoprolol metabolism by quinidine (Qd) was 200 times more potent than that of quinine (Qn), both for alpha-hydroxylation (Qd IC50 = 0.05 microM; Qn IC50 = 4 microM) and O-demethylation (Qd IC50 = 0.05 microM; Qn IC50 = 4 microM). Negligible metabolism of tolbutamide and S-mephenytoin, substrates of the 2C sub-family, and of p-nitrophenol, a substrate of CYP2E1, was detected, although a trace of the N-deethylated metabolite of lignocaine, thought to be metabolised by CYP3A4, was detected with microsomes from CYP2D6-expressing yeast cells. The results indicate that yeast cells containing human CYP2D6 cDNA express a functionally active form of the enzyme, the immunochemical and catalytic properties of which are consistent with those of human liver.
journal_name
Biochem Pharmacoljournal_title
Biochemical pharmacologyauthors
Ellis SW,Ching MS,Watson PF,Henderson CJ,Simula AP,Lennard MS,Tucker GT,Woods HFdoi
10.1016/0006-2952(92)90394-xsubject
Has Abstractpub_date
1992-08-18 00:00:00pages
617-20issue
4eissn
0006-2952issn
1873-2968pii
0006-2952(92)90394-Xjournal_volume
44pub_type
杂志文章abstract::Primary hepatocyte cultures derived from rat, rabbit, guinea pig and monkey have been treated in vitro with metabolites of di(2-ethylhexyl)phthalate, i.e. mono(2-ethylhexyl)phthalate (MEHP), mono(5-carboxy-2-ethylpentyl)phthalate (metabolite V) and mono(2-ethyl-5-oxohexyl)phthalate (metabolite VI). In rat hepatocyte c...
journal_title:Biochemical pharmacology
pub_type: 杂志文章
doi:10.1016/0006-2952(93)90223-j
更新日期:1993-06-22 00:00:00
abstract::The flavone L86-8275 [(-)cis-5,7-dihydroxy-2-(2-chlorophenyl)-8-[4-(3-hydroxy-1-methyl)- piperidinyl]-4H-1-benzopyran-4-one] delayed the progression of aphidicolin-synchronized MDA-468 breast carcinoma cells through S phase and prevented progression through G2. L86-8275 prevented the G2-related increase in histone H1 ...
journal_title:Biochemical pharmacology
pub_type: 杂志文章
doi:10.1016/0006-2952(93)90590-s
更新日期:1993-11-17 00:00:00
abstract::This article has been retracted consistent with Elsevier Policy on Article Withdrawal. Please see . The Publisher apologises for any inconvenience this may cause. ...
journal_title:Biochemical pharmacology
pub_type: 杂志文章
doi:10.1016/j.bcp.2006.03.026
更新日期:2006-04-18 00:00:00
abstract::High-affinity binding of [3H](+/-)2-amino-6,7-dihydroxy-1,2,3,4-tetrahydronaphthalene [( 3H]-ADTN) was improved by use of a subcellular fraction (P4) of tissue obtained from calf brain. The highest concentration of binding sites was found in caudate nucleus which was evaluated extensively. Binding of 0.5 nM [3H]-ADTN ...
journal_title:Biochemical pharmacology
pub_type: 杂志文章
doi:10.1016/0006-2952(83)90391-x
更新日期:1983-10-01 00:00:00
abstract::Inflammatory bowel disease (IBD) is an incurable disease which affects millions of people in industrialized countries. Anecdotal and scientific evidence suggests that Cannabis use may have a positive impact in IBD patients. Here, we investigated the effect of cannabigerol (CBG), a non-psychotropic Cannabis-derived can...
journal_title:Biochemical pharmacology
pub_type: 杂志文章
doi:10.1016/j.bcp.2013.01.017
更新日期:2013-05-01 00:00:00
abstract::Here we report that organic copper complexes can potently and selectively inhibit the chymotrypsin-like activity of the proteasome in vitro and in vivo. Several copper compounds, such as NCI-109268 and bis-8-hydroxyquinoline copper(II) [Cu(8-OHQ)(2)], can inhibit the chymotrypsin-like activity of purified 20S proteaso...
journal_title:Biochemical pharmacology
pub_type: 杂志文章
doi:10.1016/j.bcp.2003.10.031
更新日期:2004-03-15 00:00:00
abstract::The inhibitory effects of anion channel blockers were evaluated on aggregation, intracellular Ca2+ rises, and the production of arachidonic acid metabolites in human platelets. Inhibitors included five anion channel blockers: phloretin, probenecid, pyridoxal phosphate, 4,4'-diisothiocyano-2,2'-disulfonic acid stilbene...
journal_title:Biochemical pharmacology
pub_type: 杂志文章
doi:10.1016/0006-2952(89)90069-5
更新日期:1989-07-01 00:00:00
abstract::Exposures of cultured whole rat conceptuses during organogenesis to 3-methylcholanthrene (MC; 0.025-25 microM), 5,6-benzoflavone (BNF; 5-100 microM) or benz[a]anthracene (BA; 5-100 microM) were effected by placement of each of these "MC-type" inducing agents in the culture medium at the time of explantation on day 9.5...
journal_title:Biochemical pharmacology
pub_type: 杂志文章
doi:10.1016/0006-2952(94)90467-7
更新日期:1994-11-01 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
abstract::As a group, the carcinomas represent a substantial proportion of all human malignancies, but, with relatively few exceptions, current treatments are ineffective. Modification of existing chemotherapeutic agents has not led to significant improvements in the survival of carcinoma patients, and development of new therap...
journal_title:Biochemical pharmacology
pub_type: 杂志文章,评审
doi:10.1016/0006-2952(95)02232-5
更新日期:1996-05-03 00:00:00
abstract::Cancer develops through a series of genetic changes leading to malignant transformation. Numerous gene and pathways involved in stages of progression to frank malignancy have been elucidated. These genetic changes result in aberrations in fundamental cellular processes controlling proliferation, apoptosis, differentia...
journal_title:Biochemical pharmacology
pub_type: 杂志文章
doi:10.1016/j.bcp.2006.03.004
更新日期:2006-08-28 00:00:00
abstract::Calcium signaling robustly inhibits AC6 activity in membrane preparations and in intact cells via capacitative calcium entry (CCE). However, the release of intracellular calcium has not been demonstrated to robustly alter AC6 signaling and activation of Galpha(q)-coupled receptors in tissues that express AC6 enhances ...
journal_title:Biochemical pharmacology
pub_type: 杂志文章
doi:10.1016/j.bcp.2005.04.007
更新日期:2005-07-01 00:00:00
abstract::Four pseudo-symmetrical tamoxifen derivatives, RID-B (13), RID-C (14), RID-D (15), and bis(dimethylaminophenetole) (16), were synthesized via the novel three-component coupling reaction, and the structure-activity relationships of these pseudo-symmetrical tamoxifen derivatives were examined. It was discovered that 13 ...
journal_title:Biochemical pharmacology
pub_type: 杂志文章
doi:10.1016/j.bcp.2007.11.005
更新日期:2008-03-01 00:00:00
abstract::With the completion of the genome of Mycobacterium tuberculosis comes the promise of a new generation of potent drugs to combat the emerging epidemic of multiply drug-resistant isolates. Translating this genomic information into realistic assays, valid targets, and preclinical drug candidates represents the next great...
journal_title:Biochemical pharmacology
pub_type: 杂志文章
doi:10.1016/s0006-2952(99)00253-1
更新日期:2000-02-01 00:00:00
abstract::Two antitumor antibiotics doxorubicin and daunorubicin were tested for their ability to influence the activation of protein kinase C in human platelets. Daunorubicin was found to inhibit the phosphorylation of the 40 K PKC substrate induced by thrombin and 12-O-tetradecanoyl-phorbol-13-acetate as well as the phosphory...
journal_title:Biochemical pharmacology
pub_type: 杂志文章
doi:10.1016/0006-2952(88)90702-2
更新日期:1988-09-15 00:00:00
abstract::Oxidative damage of creatine kinase (CK) induced by Adriamycin((R)) (ADM) with peroxidase was investigated using horseradish peroxidase (HRP). ADM oxidatively inactivated CK during its interaction with HRP in the presence of H(2)O(2) (HRP-H(2)O(2)). The red color of ADM was lost during oxidation by HRP-H(2)O(2). Addin...
journal_title:Biochemical pharmacology
pub_type: 杂志文章
doi:10.1016/s0006-2952(00)00303-8
更新日期:2000-07-01 00:00:00
abstract::We have investigated a series of novel 4-aminoquinoline analogues related to amodiaquine, that possess side chain modifications designed to influence both drug pKa and lipophilicity. These compounds have been used to determine the influence of physicochemical properties on antimalarial activity against, and accumulati...
journal_title:Biochemical pharmacology
pub_type: 杂志文章
doi:10.1016/0006-2952(96)00354-1
更新日期:1996-09-13 00:00:00
abstract::Griseofulvin is an anti-fungal drug whose mechanism of action is directed against microtubules. Although it inhibits the assembly of mammalian brain tubulin, its binding to tubulin has not been directly measured successfully. We have examined the interaction of griseofulvin with tubulin fluorometrically by measuring t...
journal_title:Biochemical pharmacology
pub_type: 杂志文章
doi:10.1016/0006-2952(95)02406-9
更新日期:1996-04-12 00:00:00
abstract::Only very low levels of peroxidase activity were detected in castrated male hamster kidneys [1.0 +/- 0.8(S.E.) units/g protein], and chronic estrogen administration, either diethylstilbestrol (DES) or 17 beta-estradiol, for 1-5 months did not result in any appreciable increase in this activity. In contrast, hamster li...
journal_title:Biochemical pharmacology
pub_type: 杂志文章
doi:10.1016/0006-2952(83)90529-4
更新日期:1983-02-01 00:00:00
abstract::A 4',5'-unsaturated 5'-fluoroadenosine inhibitor of S-adenosyl-L-homocysteine hydrolase (SAH hydrolase; EC 3.3.1.1), MDL 28842, was found to inhibit markedly the growth of Plasmodium falciparum in vitro and Plasmodium berghei in mice. Inhibition of P. berghei growth was associated with a large increase in the concentr...
journal_title:Biochemical pharmacology
pub_type: 杂志文章
doi:10.1016/0006-2952(90)90562-y
更新日期:1990-08-01 00:00:00
abstract::Glucose metabolism and hemoglobin reactivity in intact human erythrocytes were assessed in the presence of the tryptophan metabolites, 3-hydroxyanthranilate (3-HAT), quinolinate and picolinate. Of these compounds, only 3-HAT altered red cell oxidative status by inducing, in a dose-dependent manner, formation of methem...
journal_title:Biochemical pharmacology
pub_type: 杂志文章
doi:10.1016/0006-2952(89)90301-8
更新日期:1989-05-15 00:00:00
abstract::Chronic treatment with a low dose of reserpine (0.1 mg/kg) caused rats to become hyperactive in the "open field" apparatus. When mianserin (5 mg/kg) or the selective serotonin uptake inhibitor ORG. 6582 (5 mg/kg) was chronically administered in combination with reserpine, the hyperactivity was attenuated. Both antidep...
journal_title:Biochemical pharmacology
pub_type: 杂志文章
doi:10.1016/0006-2952(83)90329-5
更新日期:1983-05-15 00:00:00
abstract::Cyclic guanosine 3'-5'-monophosphate (cGMP) has recently been shown to constitute a second messenger for Xenopus laevis melatonin Mel1c receptors. To verify whether cGMP levels are also modulated by mammalian melatonin receptors, we cloned the genes encoding the human Mel1a and Mel1b receptor subtypes and expressed th...
journal_title:Biochemical pharmacology
pub_type: 杂志文章
doi:10.1016/s0006-2952(99)00134-3
更新日期:1999-08-15 00:00:00
abstract::Methotrexate (MTX) is a chemotherapy agent linked to cognitive deficits in cancer patients received chemotherapy treatment. MTX decreases cell proliferation in the hippocampus, which is concomitant with cognitive deficits in animal models. The present study aimed to investigate the disadvantages of MTX on cognition as...
journal_title:Biochemical pharmacology
pub_type: 杂志文章
doi:10.1016/j.bcp.2019.02.010
更新日期:2019-05-01 00:00:00
abstract::Membranes of neuroblastoma N1E-115 cells contain a specific protein carboxyl methyltransferase that methylates a 70 kD protein and a group of 21-23 kD proteins which are tightly bound to the membranes. The enzyme catalyzes the transfer of [methyl-3H] groups from [methyl-3H]S-adenosyl-L-methionine (Km = 0.22 microM) to...
journal_title:Biochemical pharmacology
pub_type: 杂志文章
doi:10.1016/0006-2952(90)90405-a
更新日期:1990-09-15 00:00:00
abstract::The antimicrobial peptide human beta-defensin-3 (hBD-3) is produced by epidermal keratinocytes and protects the skin from infections. This peptide induces the release of a lipid mediator, prostaglandin D(2) from dermal mast cells. Prostaglandin D(2) binds to cell-surface G protein-coupled receptors, D prostanoid recep...
journal_title:Biochemical pharmacology
pub_type: 杂志文章
doi:10.1016/j.bcp.2009.11.012
更新日期:2010-04-01 00:00:00
abstract::Several growth factor receptors undergo shedding from the cell surface as a result of limited proteolysis via mechanisms that are at present poorly understood. By Western blotting of the conditioned media and cell lysates of several cell lines expressing the hepatocyte growth factor receptor, we found that suramin, a ...
journal_title:Biochemical pharmacology
pub_type: 杂志文章
doi:10.1016/0006-2952(95)00219-p
更新日期:1995-09-28 00:00:00
abstract::MRP1 overexpression in multidrug-resistant cancer cells has been shown to be responsible for collateral sensitivity to some flavonoids that stimulate a huge MRP1-mediated GSH efflux. This massive GSH depletion triggers the death of these cancer cells. We describe here that bivalent flavonoid dimers strikingly stimulat...
journal_title:Biochemical pharmacology
pub_type: 杂志文章
doi:10.1016/j.bcp.2016.10.013
更新日期:2017-01-15 00:00:00
abstract::Rat, rabbit and human serum albumins were immobilized on an HPLC stationary phase, and the resulting phases were tested for their abilities to determine the extent and enantioselectivity of ligand binding to the respective albumins. A series of achiral and chiral compounds were chromatographed on the phases including ...
journal_title:Biochemical pharmacology
pub_type: 杂志文章
doi:10.1016/0006-2952(93)90478-f
更新日期:1993-10-05 00:00:00
abstract::The effects of 2,5-hexanedione (2,5 HD) on skeletal proteins of red blood cells (RBCs) were investigated both in vitro (human RBCs) and in vivo in male Sprague-Dawley rats which had been treated with the drug for several days. We found that 2,5 HD induced the following major changes in the electrophoretic pattern of t...
journal_title:Biochemical pharmacology
pub_type: 杂志文章
doi:10.1016/0006-2952(89)90557-1
更新日期:1989-08-15 00:00:00