Abstract:
:Cytosolic liver acetyl-CoA:arylamine N-acetyltransferase (EC 2.3.1.5) from homozygous rapid acetylator rabbits (strain III/J) was purified to homogeneity as judged by gel filtration sodium dodecyl sulfate-polyacrylamide disc gel electrophoresis and isoelectrofocusing. The isoelectric point was estimated to be 5.2. The molecular weight was determined to be 33,500 by sodium dodecyl sulfate-polyacrylamide disc gel electrophoresis and 33,000 by Sephacryl S-200 gel filtration. The amino acid composition is reported and 16 tryptic peptides were sequenced by Edmann degradation, including a peptide from which a very specific oligonucleotide probe can be synthesized. The enzyme contained neither amino sugars nor cofactors. A broad pH optimum from pH 5.9 to 8.6 was observed. N-Acetyltransferase activity showed a strong dependency on the salt concentration. From the influence of the basicity of the acceptor amine on the maximum velocity, it was concluded that the formation of the covalent acetyl-enzyme intermediate is the rate-limiting step in the N-acetyltransferase-catalyzed acetylation of amines. The covalent intermediate reacts, then, in a fast step with the acceptor amine, when using aniline derivatives with pKa values ranging from 5.65 to 1.74. However, with the weakly basic 4-nitroaniline, the acetyltransfer from the catalytic intermediate to the amine seems to be rate-limiting. A structure-activity study of 30 aniline derivatives that differ in hydrophobicity, position, size, charge, and number of substituents showed that some ortho-substituted derivatives were not acetylated.
journal_name
Mol Pharmacoljournal_title
Molecular pharmacologyauthors
Andres HH,Vogel RS,Tarr GE,Johnson L,Weber WWsubject
Has Abstractpub_date
1987-04-01 00:00:00pages
446-56issue
4eissn
0026-895Xissn
1521-0111journal_volume
31pub_type
杂志文章abstract::Chronic morphine treatment has been shown to produce constitutive activation of mu-opioid receptors, and this transition might contribute to the development of tolerance and dependence. The apparent ability of chronic morphine to increase the spontaneous, agonist-independent activation of mu-opioid receptors may be un...
journal_title:Molecular pharmacology
pub_type: 杂志文章
doi:10.1124/mol.60.1.53
更新日期:2001-07-01 00:00:00
abstract::Cross-talk between G protein-coupled receptors and protein tyrosine kinases is well established, but the phenotypic consequences of these signaling interactions are not completely understood. To investigate the role of Src family kinases in mitogenic signaling by G protein-coupled receptors, we used genetic and pharma...
journal_title:Molecular pharmacology
pub_type: 杂志文章
doi:10.1124/mol.104.010546
更新日期:2005-06-01 00:00:00
abstract::Stimulation of N-methyl-D-aspartate (NMDA) receptors is believed to underlie long-term memory formation, and excessive NMDA receptor activation has been linked to several neuropathological conditions. Phosphorylation and activation of p42/44 mitogen-activated protein kinase (ERK) is believed to mediate many of these e...
journal_title:Molecular pharmacology
pub_type: 杂志文章
doi:10.1124/mol.104.005447
更新日期:2005-04-01 00:00:00
abstract::Rates of glucuronidation were measured at high substrate concentrations in specific zones of the liver lobule using micro-light guides placed on periportal and pericentral regions on the surface of livers from phenobarbital-treated rats. Livers were perfused with sulfate-free buffer under normoxic conditions, and fluo...
journal_title:Molecular pharmacology
pub_type: 杂志文章
doi:
更新日期:1984-05-01 00:00:00
abstract::There are now several examples of single G protein-coupled receptors to which binding of specific agonists causes differential effects on the associated signaling pathways. The dopamine D(2) receptor is of special importance because the selective activation of functional pathways has been shown both in vitro and in si...
journal_title:Molecular pharmacology
pub_type: 杂志文章
doi:10.1124/mol.66.1.97
更新日期:2004-07-01 00:00:00
abstract::In this study, the expression of CYP26 is examined in relation to retinoid-induced mucosecretory differentiation in human tracheobronchial epithelial (HTBE) cells and compared with that in human lung carcinoma cell lines. In HTBE cells, retinoic acid (RA) inhibits squamous differentiation and induces mucous cell diffe...
journal_title:Molecular pharmacology
pub_type: 杂志文章
doi:10.1124/mol.58.3.483
更新日期:2000-09-01 00:00:00
abstract::Smad4, a key transcription factor in the transforming growth factor-β signaling pathway, is involved in a variety of cell physiologic and pathologic processes. Here, we characterized megakaryocyte/platelet-specific Smad4 deficiency in mice to elucidate its effect on platelet function. We found that megakaryocyte/plate...
journal_title:Molecular pharmacology
pub_type: 杂志文章
doi:10.1124/mol.116.107417
更新日期:2017-09-01 00:00:00
abstract::The carbocyclic analogue of 5-nitro-2'-deoxyuridine (NO2dUrd), in which the sugar moiety is replaced by a cyclopentane ring and which was designated C-NO2dUrd, has been evaluated for its cytostatic, antimetabolic, and antitumor properties. The following findings are noted. C-NO2dUrd is about 500- to 2000-fold less inh...
journal_title:Molecular pharmacology
pub_type: 杂志文章
doi:
更新日期:1985-05-01 00:00:00
abstract::Anthracyclines are effective anticancer agents. However, their use is limited by cardiotoxicity, an effect linked to their ability to chelate iron and to perturb iron metabolism (Mol Pharmacol 68:261-271, 2005). These effects on iron-trafficking remain poorly understood, but they are important to decipher because trea...
journal_title:Molecular pharmacology
pub_type: 杂志文章
doi:10.1124/mol.107.041335
更新日期:2008-03-01 00:00:00
abstract::Niflumic acid [2-((3-(trifluoromethyl)phenyl)amino)-3-pyridinecarboxylic acid, NFA] is a nonsteroidal anti-inflammatory drug that also blocks or modulates the gating of a wide spectrum of ion channels. Here we investigated the mechanism of channel activation by NFA on ether-a-go-go-related gene (ERG) K(+) channel subt...
journal_title:Molecular pharmacology
pub_type: 杂志文章
doi:10.1124/mol.107.043505
更新日期:2008-04-01 00:00:00
abstract::The levels of hepatic mRNAs for several enzymes involved in drug metabolism were measured following administration to rats of either phenobarbitone or 2-allyl-2-isopropylacetamide. There was a substantial elevation in the mRNA levels for cytochromes P450 IIB1, IIB2, and IIIA1, epoxide hydrolase, glutathione-S-transfer...
journal_title:Molecular pharmacology
pub_type: 杂志文章
doi:
更新日期:1990-10-01 00:00:00
abstract::Four piperazinoquinolone antibacterial drugs (norfloxacin, ciprofloxacin, enoxacin, and pipemidic acid), known to be gamma-aminobutyric acid (GABA) antagonists, fully reversed the inhibitory effect of GABA on [35S]t-butylbicyclophosphorothionate ([35S] TBPS) binding to rat brain membranes in vitro. Twelve indomethacin...
journal_title:Molecular pharmacology
pub_type: 杂志文章
doi:
更新日期:1993-05-01 00:00:00
abstract::We show here that arsenite (As(3+)) elicits multiple effects on gene control, such as the interruption of cell cycle control by initiating G(2)/M arrest as well as inhibiting the aryl hydrocarbon (Ah) receptor-mediated 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD)-inducible expression of CYP1A1. This raises the question ...
journal_title:Molecular pharmacology
pub_type: 杂志文章
doi:10.1124/mol.104.006130
更新日期:2005-04-01 00:00:00
abstract::In the previous paper [Mol. Pharmacol. 23:671-680 (1983)] it was shown that ouabain enhances the exocytotic release of catecholamines from isolated bovine adrenal medullary cells. This effect is dependent upon extracellular sodium, but persists in the nominal absence of calcium. In this paper the study has been extend...
journal_title:Molecular pharmacology
pub_type: 杂志文章
doi:
更新日期:1983-05-01 00:00:00
abstract::Ca-dependent, K-stimulated 86Rb efflux, a measure of Ca-activated K conductance in rat brain synaptosomes, was blocked by phenothiazines and haloperidol. Micromolar concentrations of the phenothiazines, fluphenazine and trifluoperazine, and haloperidol, a non-phenothiazine antipsychotic and calmodulin antagonist, sele...
journal_title:Molecular pharmacology
pub_type: 杂志文章
doi:
更新日期:1988-02-01 00:00:00
abstract::Microinjection, but not extracellular application, of cytidine-5'-diphosphate-D-glucose (CDPG) has been shown to elicit Ca(2+)-dependent currents in Xenopus laevis oocytes. These responses were comparable to those of inositol-1,4,5-trisphosphate (InsP3) in being both rapid and dose dependent. For example, maximal ampl...
journal_title:Molecular pharmacology
pub_type: 杂志文章
doi:
更新日期:1996-02-01 00:00:00
abstract::Acute cannabidiol treatment of mice inactivated hepatic microsomal cytochrome P-450IIIA (P-450IIIA) and markedly inhibited in vitro cannabinoid metabolism. Antibodies raised against purified P-450IIIA inhibited the microsomal formation of quantitatively minor cannabinoid metabolites but had no effect on the major meta...
journal_title:Molecular pharmacology
pub_type: 杂志文章
doi:
更新日期:1991-08-01 00:00:00
abstract::P2X receptors are trimeric membrane proteins. When they bind extracellular ATP, a conformational change occurs that opens a transmembrane ion channel. The ATP-binding pocket is formed in a cleft between two subunits, and a critical amino acid residue for ATP contact is Lys⁶⁹ (P2X2 numbering). In the present work, we s...
journal_title:Molecular pharmacology
pub_type: 杂志文章
doi:10.1124/mol.112.080903
更新日期:2012-10-01 00:00:00
abstract::We have investigated various nitric oxide (NO) synthase inhibitors for their affinity and selectivity toward the three human isoenzymes in radioligand binding experiments. Therefore, we developed the new radioligand [(3)H]2-amino-4-picoline to measure binding of these compounds to the three human NO synthase (NOS) iso...
journal_title:Molecular pharmacology
pub_type: 杂志文章
doi:
更新日期:2000-11-01 00:00:00
abstract::Iodonium inhibition of the flavoenzymes neutrophil NADPH oxidase and cytochrome P450 reductase has been suggested to require reductive metabolism of the inhibitor to a phenyl radical. Inhibition would ultimately result from covalent attachment of phenyl radicals to either the flavin cofactor or adjacent amino acid sid...
journal_title:Molecular pharmacology
pub_type: 杂志文章
doi:
更新日期:1994-10-01 00:00:00
abstract::Systematic series of monoamines, diamines, and triamines were used to define the structural requirements for interaction at the polyamine recognition site of the N-methyl-D-aspartate receptor complex. Effects of amines on binding of [3H]MK-801 to washed synaptic plasma membranes were measured in the presence of L-glut...
journal_title:Molecular pharmacology
pub_type: 杂志文章
doi:
更新日期:1992-04-01 00:00:00
abstract::Previous studies indicated that activation of alpha 1-adrenergic receptors in BC3H-1 muscle cells (S. K. Ambler and P. Taylor, J. Biol. Chem. 261:5866-5871, 1986) and muscarinic receptors in 1321N1 astrocytoma cells (S. B. Masters, T. K. Harden, and J. H. Brown, Mol. Pharmacol. 27:325-332, 1985) resulted in the rapid ...
journal_title:Molecular pharmacology
pub_type: 杂志文章
doi:
更新日期:1987-09-01 00:00:00
abstract::Freshly isolated rat hepatocytes rapidly lose their cytochrome P450 (P450) proteins and mRNAs, with no evidence of subsequent restoration, after placement into traditional systems of primary culture on type I collagen. We examined the patterns of expression of 10 constitutively expressed P450 mRNAs in rat hepatocytes ...
journal_title:Molecular pharmacology
pub_type: 杂志文章
doi:
更新日期:1993-03-01 00:00:00
abstract::Combining chemotherapeutics to treat malignant tumors has been shown to be effective in preventing drug resistance, tumor recurrence, and reducing tumor size. We modeled combination drug therapy in PC-3 human prostate cancer cells using mixture design response surface methodology (MDRSM), a statistical technique desig...
journal_title:Molecular pharmacology
pub_type: 杂志文章
doi:10.1124/mol.117.111450
更新日期:2018-08-01 00:00:00
abstract::The anti-human immunodeficiency virus (-HIV) nucleoside analogs azidothymidine (AZT), dideoxycytidine (ddC), dideoxyinosine (ddl), dideoxydidehydrothymidine (D4T), and dideoxydidehydrocytidine (D4C) and the anticancer drug cytosine arabinoside (AraC) were compared for their effects on the mitochondrial DNA (mtDNA) con...
journal_title:Molecular pharmacology
pub_type: 杂志文章
doi:
更新日期:1991-05-01 00:00:00
abstract::Previous studies suggest that selective antagonists of specific subtypes of muscarinic acetylcholine receptors (mAChRs) may provide a novel approach for the treatment of certain central nervous system (CNS) disorders, including epileptic disorders, Parkinson's disease, and dystonia. Unfortunately, previously reported ...
journal_title:Molecular pharmacology
pub_type: 杂志文章
doi:10.1124/mol.109.056531
更新日期:2009-08-01 00:00:00
abstract::A number of different agonists activate G protein-coupled receptors to stimulate adenylyl cyclase (AC), increase cAMP formation, and promote relaxation in vascular smooth muscle. To more fully understand this stimulation of AC, we assessed the expression, regulation, and compartmentation of AC isoforms in rat aortic s...
journal_title:Molecular pharmacology
pub_type: 杂志文章
doi:10.1124/mol.62.5.983
更新日期:2002-11-01 00:00:00
abstract::A central axiom of ligand-receptor theory is that agonists bind more tightly to active than to inactive receptors. However, measuring agonist affinity in inactive receptors is confounded by concomitant activation. We identified a cysteine substituted mutant γ-aminobutyric acid type A (GABAA) receptor with unique chara...
journal_title:Molecular pharmacology
pub_type: 杂志文章
doi:10.1124/mol.112.084558
更新日期:2013-06-01 00:00:00
abstract::Mammalian A2-adenosine receptor binding subunits (A2AR) can be visualized by covalent labeling with the photoaffinity crosslinking ligand 125I-2-[4-[2-[2-[(4-aminophenyl)methylcarbonylamino] ethylaminocarbonyl]ethyl]phenyl]ethylamino-5'-N-ethylcarboxamidoad enosine or directly with the azide derivative described in th...
journal_title:Molecular pharmacology
pub_type: 杂志文章
doi:
更新日期:1990-08-01 00:00:00
abstract::The metabotropic glutamate receptor subtype 5 (mGlu5) activates calcium mobilization via binding of glutamate, the major excitatory neurotransmitter in the central nervous system. Allosteric modulation of the receptor has recently emerged as a promising alternative method of regulation to traditional regulation throug...
journal_title:Molecular pharmacology
pub_type: 杂志文章
doi:10.1124/mol.105.016139
更新日期:2005-12-01 00:00:00