Abstract：
:The aryl hydrocarbon receptor (AhR) is a transcriptional enhancer that is activated by the binding of 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) and related toxic xenobiotics, as well as some naturally occurring compounds. Ligand binding initiates 1) dissociation of the ligand-bound monomeric AhR from the ligand-unoccupied multimeric complex and 2) biochemical and/or conformational changes that enable association of the ligand-bound monomer with other proteins. This heteromeric complex has high affinity for specific elements [dioxin-responsive elements (DREs)] in the regulatory regions of a number of structural genes, the induction and/or repression of which may be a mechanism of toxicity of TCDD. We have developed a relatively simple and rapid procedure that enables purification to homogeneity of a TCDD-bound receptor complex. The final step of purification is based on binding to an oligonucleotide containing the specific DRE sequence that is found in the upstream region of the CYP1A1 structural gene. The purified complex retains in vitro DRE-binding function. Silver staining and Western blot analyses demonstrate that the complex consists of the AhR ligand-binding monomer of approximately 104 kDa, plus two proteins (94 and 96 kDa) that are recognized by antibodies prepared against the AhR nuclear translocator protein. Previous attempts to purify a DRE-binding form of the AhR were unsuccessful because of dissociation of the complex during chromatography; this is the first report of an isolated functional complex. The purified preparation will be valuable in further studies of receptor regulation and function.
journal_name
Mol Pharmacoljournal_title
Molecular pharmacologyauthors
Henry EC,Rucci G,Gasiewicz TAsubject
Has Abstractpub_date
1994-12-01 00:00:00pages
1022-7issue
6eissn
0026-895Xissn
1521-0111journal_volume
46pub_type
杂志文章abstract：:We present a mechanism for agonist-promoted alpha(2A)-adrenergic receptor (alpha(2A)-AR) activation based on structural, pharmacological, and theoretical evidence of the interactions between phenethylamine ligands and alpha(2A)-AR. In this study, we have: 1) isolated enantiomerically pure phenethylamines that differ b...
journal_title：Molecular pharmacology
pub_type： 杂志文章
doi：10.1124/mol.59.5.1343
更新日期：2001-05-01 00:00:00
abstract：:Nitric oxide (NO) promotes retinal and choroidal neovascularization, although different isoforms of nitric-oxide synthetase (NOS) are critical in each. Deficiency of endothelial NOS (eNOS) suppresses retinal but not choroidal neovascularization, whereas deficiency of neuronal NOS (nNOS) or inducible NOS (iNOS) suppres...
journal_title：Molecular pharmacology
pub_type： 杂志文章
doi：10.1124/mol.62.3.539
更新日期：2002-09-01 00:00:00
abstract：:Equilibrative nucleoside transporters (ENTs) 1 and 2 facilitate nucleoside transport across the blood-testis barrier (BTB). Improving drug entry into the testes with drugs that use endogenous transport pathways may lead to more effective treatments for diseases within the reproductive tract. In this study, CRISPR/CRIS...
journal_title：Molecular pharmacology
pub_type： 杂志文章
doi：10.1124/molpharm.120.000169
更新日期：2021-02-01 00:00:00
abstract：:Voltage-gated potassium (Kv) channels regulate many physiological functions and represent important therapeutic targets in the treatment of several clinical disorders. Although some of these channels have been well-characterized, the study of others, such as Kv3 channels, has been hindered because of limited pharmacol...
journal_title：Molecular pharmacology
pub_type： 杂志文章
doi：10.1124/mol.105.011064
更新日期：2005-05-01 00:00:00
abstract：:Consequent to agonist exposure, many G protein-coupled receptors undergo sequestration or internalization. Results with receptors linked to adenylate cyclase, such as the beta 2-adrenergic receptor, or receptors linked to phospholipase C (PLC) have provided conflicting results regarding the role of second messenger-de...
journal_title：Molecular pharmacology
pub_type： 杂志文章
doi：
更新日期：1994-09-01 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
abstract：:In rat pancreatic zymogen granules (ZG), an ATP-sensitive K(+) conductance and a Cl(-) conductance have been characterized that are inversely regulated by an approximately 65-kDa multidrug resistance P-glycoprotein (mdr1) gene product. In search of a label for purification of this protein, we found that the dihydropyr...
journal_title：Molecular pharmacology
pub_type： 杂志文章
doi：
更新日期：2000-02-01 00:00:00
abstract：:The peroxisome proliferator-activated receptors (PPARs) represent pharmacological target molecules to improve insulin resistance in type 2 diabetes mellitus. Here we assessed a functional connection between pharmacological activation of PPAR and vascular endothelial growth factor (VEGF) expression in keratinocytes and...
journal_title：Molecular pharmacology
pub_type： 杂志文章
doi：10.1124/mol.108.049395
更新日期：2008-10-01 00:00:00
abstract：:The pharmacological effects of angiotensin II (AII) are potently inhibited by several peptide and recently synthesized nonpeptide AII receptor antagonists. The interaction of sarcosine1, isoleucine8-AII (sarile), sarcosine1,O-methyltyrosine4-AII (sarmesin), and the nonpeptide AII antagonists 2-n-butyl-4-chloro-5- hydr...
journal_title：Molecular pharmacology
pub_type： 杂志文章
doi：
更新日期：1992-06-01 00:00:00
abstract：:GABAA receptors are modulated by a variety of compounds, including the neurosteroids and barbiturates. Although the effects of barbiturates on alphabetagamma isoforms, thought to dominate phasic (synaptic) GABAergic inhibition, have been extensively studied, the effects of pentobarbital on kinetic properties of alphab...
journal_title：Molecular pharmacology
pub_type： 杂志文章
doi：10.1124/mol.104.002543
更新日期：2004-10-01 00:00:00
abstract：:The alpha2-adrenergic receptors (alpha2-ARs) mediate signals to intracellular second messengers via guanine nucleotide binding proteins. Three human genes encoding alpha2-AR subtypes (alpha2A, alpha2B, alpha2C) have been cloned. Several chemical compounds display subtype differences in their binding and/or functional ...
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：:The mammalian copper transporter 1 (CTR1) is responsible for the uptake of copper from the extracellular space. In this study, we used an isogenic pair of CTR1(+/+) and CTR1(-/-) mouse embryo fibroblasts to examine the contribution of CTR1 to the influx of cisplatin (DDP), carboplatin (CBDCA), oxaliplatin (L-OHP), and...
journal_title：Molecular pharmacology
pub_type： 杂志文章
doi：10.1124/mol.108.052381
更新日期：2009-02-01 00:00:00
abstract：:We have reported previously that the transmembrane domains of the cholecystokinin-B/gastrin receptor (CCK-BR) comprise a putative ligand binding pocket. In the present study, we examined whether amino acid substitutions within the CCK-BR pocket altered the affinities and/or functional activities of L-365,260 (the prot...
journal_title：Molecular pharmacology
pub_type： 杂志文章
doi：10.1124/mol.54.5.857
更新日期：1998-11-01 00:00:00
abstract：:The chemokine receptor CCR2 is a G protein-coupled receptor that is activated primarily by the endogenous CC chemokine ligand 2 (CCL2). Many different small-molecule antagonists have been developed to inhibit this receptor, as it is involved in a variety of diseases characterized by chronic inflammation. Unfortunately...
journal_title：Molecular pharmacology
pub_type： 杂志文章
doi：10.1124/mol.113.086850
更新日期：2013-10-01 00:00:00
abstract：:The local anesthetic-like Na+ channel-blocking drug [3H]PD85639 [alpha-([4-3H]phenyl)-N-[3-(2,6-dimethyl-1-piperizinyl)-alpha-prop yl] [4-3H]benzeneacetamide] binds specifically to receptor sites on Na+ channels in intact synaptosomes and synaptosomal membranes, purified and reconstituted Na+ channels, and type IIA Na...
journal_title：Molecular pharmacology
pub_type： 杂志文章
doi：
更新日期：1993-06-01 00:00:00
abstract：:Although α7 nicotinic acetylcholine receptors are considered potentially important therapeutic targets, the development of selective agonists has been stymied by the α7 receptor's intrinsically low probability of opening (P(open)) and the concern that an agonist-based therapeutic approach would disrupt endogenous chol...
journal_title：Molecular pharmacology
pub_type： 杂志文章
doi：10.1124/mol.111.074302
更新日期：2011-12-01 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：:Labeled histidine was taken up into rat leukemic basophil 2H3 cells by a system with high affinity for histidine and then decarboxylated to form histamine. Uptake was partially inhibited and decarboxylation was completely blocked by alpha-fluoromethylhistidine (alpha-FMH) at concentrations of 10-100 microM. alpha-FMH ...
journal_title：Molecular pharmacology
pub_type： 杂志文章
doi：
更新日期：1985-08-01 00:00:00
abstract：:Using an oligonucleotide based on the sequence of a porcine brain muscarinic receptor cDNA, we recently cloned four distinct muscarinic receptors from the rat and human genomes. In the present study we transfected the rat homolog of the porcine brain muscarinic receptor cDNA into A9 L cells using a mammalian expressio...
journal_title：Molecular pharmacology
pub_type： 杂志文章
doi：
更新日期：1987-10-01 00:00:00
abstract：:Kinetics of the interactions between the neuromuscular blocker alcuronium, the specific muscarinic antagonist N-[methyl-3H] methyl scopolamine ([3H]NMS), and muscarinic receptors were investigated in homogenates of rat heart atria. Two effects of alcuronium on the binding of [3H]NMS could be distinguished. (a) Alcuron...
journal_title：Molecular pharmacology
pub_type： 杂志文章
doi：
更新日期：1994-04-01 00:00:00
abstract：:Potassium channels play fundamental roles in physiology. Chemically diverse drugs bind in the pore region of K+ channels. Here, we homology-modeled voltage- and Ca2+-gated K+ channel BK and voltage-gated Kv1.3 using the X-ray structures of MthK and Kv1.2, respectively, and simulated the binding of d-tubocurarine in th...
journal_title：Molecular pharmacology
pub_type： 杂志文章
doi：10.1124/mol.105.017970
更新日期：2006-04-01 00:00:00
abstract：:Receptors for the serine protease thrombin and for lysophospholipids are coupled to G proteins and control a wide range of cellular functions, including mitogenesis. Activators of these receptors are present in blood, and can enter the brain during central nervous system (CNS) injury. Reactive astrogliosis, a prominen...
journal_title：Molecular pharmacology
pub_type： 杂志文章
doi：10.1124/mol.64.5.1199
更新日期：2003-11-01 00:00:00
abstract：:The effect of the neuromuscular blocker alcuronium on the binding of N-[3H]-methylscopolamine [( 3H]NMS) and l-[3H]quinuclidinylbenzilate ([3H]QNB) to muscarinic binding sites in rat heart atria, longitudinal smooth muscle of the ileum, cerebral cortex, cerebellum, and submaxillary glands was measured using filtration...
journal_title：Molecular pharmacology
pub_type： 杂志文章
doi：
更新日期：1990-11-01 00:00:00
abstract：:The mechanism of adenylyl cyclase desensitization by carbachol, an agent that stimulates polyphosphoinositide hydrolysis, was studied in thyroid cells. Incubation of cultured dog thyroid cells with 10 microM carbachol for 2-4 hr reduced the subsequent thyrotropic hormone (TSH) stimulation of adenylyl cyclase activity ...
journal_title：Molecular pharmacology
pub_type： 杂志文章
doi：
更新日期：1992-01-01 00:00:00
abstract：:The antiherpetic agent (E)-5-(2-bromovinyl)-2'-deoxyuridine (BVDU) was found to be an efficient substrate for recombinant Drosophila melanogaster-deoxyribonucleoside kinase with a K(m) of 4.5 microM and a V(max) of 400 nmol/microg protein/h compared with 1.3 microM and 62.5 nmol/microg protein/h, respectively, for the...
journal_title：Molecular pharmacology
pub_type： 杂志文章
doi：10.1124/mol.57.4.811
更新日期：2000-04-01 00:00:00
abstract：:The highly specialized metabotropic glutamate receptor type 6 (mGluR6) is postsynaptically localized and expressed only in the dendrites of ON bipolar cells. Upon activation of mGluR6 by glutamate released from photoreceptors, a nonselective cation channel is inhibited, causing these cells to hyperpolarize. Mutations ...
journal_title：Molecular pharmacology
pub_type： 杂志文章
doi：10.1124/mol.109.058628
更新日期：2009-11-01 00:00:00
abstract：:Anaplastic thyroid carcinoma (ATC) is among the most aggressive malignancies known and is characterized with rapid growth, early invasion, and complete refractoriness to current therapies. Here we report that triptolide, a small molecule from a Chinese herb, could potently inhibit proliferation in vitro, angiogenesis ...
journal_title：Molecular pharmacology
pub_type： 杂志文章
doi：10.1124/mol.108.052605
更新日期：2009-04-01 00:00:00
abstract：:N-formyl peptide receptor (FPR1) and N-formyl peptide receptor-like 1 (FPRL1, now known as FPR2) are G protein-coupled receptors involved in host defense and sensing cellular dysfunction. Because of the potential for FPR1/FPR2 as a therapeutic target, our recent high-throughput screening efforts have focused on the id...
journal_title：Molecular pharmacology
pub_type： 杂志文章
doi：10.1124/mol.109.060673
更新日期：2010-02-01 00:00:00
abstract：:The successful synthesis of dolastatin 11, a depsipeptide originally isolated from the mollusk Dolabella auricularia, permitted us to study its effects on cells. The compound arrested cells at cytokinesis by causing a rapid and massive rearrangement of the cellular actin filament network. In a dose-and time-dependent ...
journal_title：Molecular pharmacology
pub_type： 杂志文章
doi：10.1124/mol.59.3.462
更新日期：2001-03-01 00:00:00
abstract：:We have recently demonstrated that the alpha 2-adrenergic radioligand [3H]idazoxan also labels additional sites that do not recognize catecholamines but bind with high affinity several chemically distinct drugs previously assumed to be highly selective for alpha 2-adrenergic receptors [Mol. Pharmacol. 35:324-330 (1989...
journal_title：Molecular pharmacology
pub_type： 杂志文章
doi：
更新日期：1990-01-01 00:00:00
