Abstract:
:The relations between the single high affinity binding sites for azapropazone, phenylbutazone, chlorpropamide, sulfathiazole, and iophenoxate and the binding regions of human serum albumin represented by the marker ligands diazepam, phenol red, salicylate, and warfarin were examined by a series of competition experiments. Binding was determined by equilibrium dialysis at pH 7.0. In order to ensure an accurate analysis of the competition experiment, the number of moles of ligand bound per mole of protein was usually 0.4 or less to minimize ligand binding to weaker sites. Furthermore, binding of both ligands was determined in all experiments (except for iophenozate). None of the test ligands competed with diazepam for a common high affinity binding site, but, surprisingly, they were all able to displace two or three of the other marker ligands according to a competitive scheme. These findings show, first, the existence of a particular serum albumin region for high affinity binding of diazepam. Secondly, they imply that it is not necessary to assume the existence of new drug binding regions beyond those existing for phenol red, salicylate, and warfarin. On the contrary, the relatively many examples of competitive binding indicate that the binding regions represented by the last-mentioned three marker ligands are placed quite close to each other in the albumin molecule in a common region, which is suggested to be located at subdomains 1C and 2A-B. The region must be relatively large, because in some cases independent high affinity binding of pairs of ligands is observed. It is probably also rather flexible, inasmuch as no clear relation could be found between the chemical structure of the test ligands and the two or three marker ligands with which they compete. Correlations between primary association constants and partition coefficients for both marker ligands and test ligands, in the unionized forms, between n-hexane or 1-octanol and aqueous media showed that hydrophobic forces are important for the binding processes. However, the data also showed that other attractive forces must be operative as well.
journal_name
Mol Pharmacoljournal_title
Molecular pharmacologyauthors
Kragh-Hansen Usubject
Has Abstractpub_date
1988-08-01 00:00:00pages
160-71issue
2eissn
0026-895Xissn
1521-0111journal_volume
34pub_type
杂志文章abstract::The effect of halothane on synthesis of retained and secreted proteins was investigated using isolated perfused rat livers. Anesthetic exposure rapidly inhibited synthesis of total liver proteins in a dose-dependent manner by a mechanism which appeared to involve reduced rates of both peptide chain initiation and elon...
journal_title:Molecular pharmacology
pub_type: 杂志文章
doi:
更新日期:1983-09-01 00:00:00
abstract::Our laboratory recently isolated and sequenced cDNAs encoding the microsomal flavin-containing monooxygenases (FMOs) from rabbit liver and rabbit lung. As a first step in understanding the molecular bases for the catalytic and physical differences between these enzymes, we have expressed them in COS-1 cells and compar...
journal_title:Molecular pharmacology
pub_type: 杂志文章
doi:
更新日期:1991-11-01 00:00:00
abstract::Cytokines are thought to cause the depression of cytochrome P-450 (CYP)-associated drug metabolism in humans during inflammation and infection. We have examined the role of five cytokines, i.e., interleukin-1 beta, interleukin-4, interleukin-6, tumor necrosis factor-alpha, and interferon-gamma, on the expression of CY...
journal_title:Molecular pharmacology
pub_type: 杂志文章
doi:
更新日期:1993-10-01 00:00:00
abstract::The human mu-opioid receptor (HmuOR) is a G-protein coupled receptor that mediates analgesia, euphoria and other important central and peripheral neurological functions. In this study, we found in a yeast two-hybrid screen that a protein kinase C-interacting protein (PKCI) specifically interacts with the C terminus of...
journal_title:Molecular pharmacology
pub_type: 杂志文章
doi:10.1124/mol.66.5.
更新日期:2004-11-01 00:00:00
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journal_title:Molecular pharmacology
pub_type: 杂志文章
doi:
更新日期:1994-08-01 00:00:00
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journal_title:Molecular pharmacology
pub_type: 杂志文章,评审
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更新日期:2016-12-01 00:00:00
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journal_title:Molecular pharmacology
pub_type: 杂志文章
doi:10.1124/mol.61.2.446
更新日期:2002-02-01 00:00:00
abstract::4-PIOL is a structural analog of GABA that has low efficacy at GABAA receptor CI- channels and activates a nondesensitizing CI- conductance in central neurons. We investigated the biophysical mechanisms of its low efficacy in embryonic olfactory bulb neurons, which express a limited number of GABAA receptor subunit tr...
journal_title:Molecular pharmacology
pub_type: 杂志文章
doi:
更新日期:1995-08-01 00:00:00
abstract::Adenosine receptors of the A1 and A2 subtypes were characterized in membranes from DDT1 MF-2 smooth muscle cells. These cells possess a high density of A1 adenosine receptors (Bmax = 0.8-0.9 pmol/mg of protein), as measured by both agonist and antagonist radioligands. Agonists compete for [125I]N6-[2-(4-amino-3-iodoph...
journal_title:Molecular pharmacology
pub_type: 杂志文章
doi:
更新日期:1990-02-01 00:00:00
abstract::Mutations that inhibit Kv11.1 ion channel activity contribute to abnormalities of cardiac repolarization that can lead to long QT2 (LQT2) cardiac arrhythmias and sudden death. However, for most of these mutations, nothing is known about the molecular mechanism linking Kv11.1 malfunction to cardiac death. We have previ...
journal_title:Molecular pharmacology
pub_type: 杂志文章
doi:10.1124/mol.112.077966
更新日期:2012-09-01 00:00:00
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journal_title:Molecular pharmacology
pub_type: 杂志文章
doi:10.1124/mol.59.4.939
更新日期:2001-04-01 00:00:00
abstract::The ability of chemically distinct ligands to produce different effects on the same G protein-coupled receptor (GPCR) has interesting therapeutic implications, but, if excessively propagated downstream, would introduce biologic noise compromising cognate ligand detection. We asked whether cells have the ability to lim...
journal_title:Molecular pharmacology
pub_type: 杂志文章
doi:10.1124/mol.116.106369
更新日期:2017-02-01 00:00:00
abstract::To identify novel factors or mechanisms that are important for the resistance of tissues to chemical toxicity, we have determined the mechanisms underlying the previously observed increases in resistance to acetaminophen (APAP) toxicity in the lateral nasal gland (LNG) of the male Cyp2g1-null/Cyp2a5-low mouse. Initial...
journal_title:Molecular pharmacology
pub_type: 杂志文章
doi:10.1124/mol.110.070045
更新日期:2011-04-01 00:00:00
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journal_title:Molecular pharmacology
pub_type: 杂志文章
doi:10.1124/mol.118.113233
更新日期:2019-02-01 00:00:00
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journal_title:Molecular pharmacology
pub_type: 杂志文章
doi:10.1124/mol.119.118661
更新日期:2020-06-01 00:00:00
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journal_title:Molecular pharmacology
pub_type: 杂志文章
doi:10.1124/mol.63.1.89
更新日期:2003-01-01 00:00:00
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journal_title:Molecular pharmacology
pub_type: 杂志文章
doi:
更新日期:1988-10-01 00:00:00
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journal_title:Molecular pharmacology
pub_type: 杂志文章
doi:
更新日期:1992-05-01 00:00:00
abstract::In GH3 pituitary cell homogenates, acetylcholine (ACh) (IC50 200 nM) inhibits adenylate cyclase [ATP pyrophosphate-lyase (cyclizing), EC 4.6.1.1] activity in a concentration- and GTP-dependent manner. Maximal inhibition was obtained with 10 microM ACh and corresponded to approximately a 50% decrease in basal enzyme ac...
journal_title:Molecular pharmacology
pub_type: 杂志文章
doi:
更新日期:1983-09-01 00:00:00
abstract::High expression of the aflatoxin B1 (AFB1)-8,9-epoxide-conjugating glutathione S-transferase A3 (mGSTA3) subunit in mouse liver confers intrinsic resistance to AFB1 hepatocarcinogenesis. It is not known how the gene encoding this protein is regulated. The murine mGSTA3 gene has been identified using bioinformatics. It...
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pub_type: 杂志文章
doi:10.1124/mol.64.5.1018
更新日期:2003-11-01 00:00:00
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journal_title:Molecular pharmacology
pub_type: 杂志文章
doi:
更新日期:1990-12-01 00:00:00
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journal_title:Molecular pharmacology
pub_type: 杂志文章
doi:10.1124/mol.65.3.623
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journal_title:Molecular pharmacology
pub_type: 杂志文章
doi:10.1124/mol.63.2.383
更新日期:2003-02-01 00:00:00
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journal_title:Molecular pharmacology
pub_type: 杂志文章
doi:10.1124/mol.53.3.370
更新日期:1998-03-01 00:00:00
abstract::TWIK-related K+ channel TREK1, a background leak K+ channel, has been strongly implicated as the target of several general and local anesthetics. Here, using the whole-cell and single-channel patch-clamp technique, we investigated the effect of lidocaine, a local anesthetic, on the human (h)TREK1 channel heterologousl...
journal_title:Molecular pharmacology
pub_type: 杂志文章
doi:10.1124/mol.109.056838
更新日期:2009-10-01 00:00:00
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journal_title:Molecular pharmacology
pub_type: 杂志文章
doi:
更新日期:1996-10-01 00:00:00
abstract::ORKAMBI, a combination of the corrector, lumacaftor, and the potentiator, ivacaftor, partially rescues the defective processing and anion channel activity conferred by the major cystic fibrosis-causing mutation, F508del, in in vitro studies. Clinically, the improvement in lung function after ORKAMBI treatment is modes...
journal_title:Molecular pharmacology
pub_type: 杂志文章
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更新日期:2019-10-01 00:00:00
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journal_title:Molecular pharmacology
pub_type: 杂志文章
doi:10.1124/mol.52.6.1095
更新日期:1997-12-01 00:00:00
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journal_title:Molecular pharmacology
pub_type: 杂志文章
doi:10.1124/mol.108.046979
更新日期:2008-11-01 00:00:00
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journal_title:Molecular pharmacology
pub_type: 杂志文章
doi:10.1124/mol.105.014241
更新日期:2006-02-01 00:00:00