Abstract:
:The presence and properties of the Ah receptor were examined in the guinea pig, rat, hamster, monkey, and three different strains of mice. These species and strains have demonstrated differences in sensitivity and variability of response to 2,3,7,8-tetrachlorodibenzo-p-dioxin and related compounds. All species examined, with the exception of DBA/2J mice, possess similar amounts of binding protein with high affinity for 2,3,7,8-tetrachlorodibenzo-p-dioxin in hepatic tissue. Numerous dibenzo-p-dioxin congeners and polycyclic aromatic hydrocarbons demonstrated a similar rank order ability to bind to receptor molecules from these species. When analyzed by gel-exclusion high-performance liquid chromatography, hepatic cytosolic receptors from all species eluted at volumes corresponding to a similar molecular weight range. Association of the hepatic Ah receptor with the nuclear fraction was observed in all cases following the i.p. treatment of guinea pig, rat, C57BL/6J mouse, or hamster with [3H]2,3,7,8-tetrachlorodibenzo-p-dioxin. In all species and tissues examined, with the exception of hamster duodenum and thymus, the highest concentrations of receptor were localized in the liver, lung, thymus, intestine, and kidney. Exceptionally high concentrations of receptors were also observed in guinea pig testes. These findings indicate that, despite species and tissue specific differences in the biochemical and toxicological responses to 2,3,7,8-tetrachlorodibenzo-p-dioxin and related compounds, a number of different mammalian species possess Ah receptors with similar properties. Thus, the correlative differences between certain strains of mice in terms of altered specific binding of 2,3,7,8-tetrachlorodibenzo-p-dioxin and sensitivity to this compound may be unique and not necessarily applicable to other species. Although all data indicate that the receptor mediates these responses, it appears that species- and tissue-specific differences may be determined by a number of additional factors. These results also suggest the conservation of some, as yet unknown, functional role of the receptor molecule.
journal_name
Mol Pharmacoljournal_title
Molecular pharmacologyauthors
Gasiewicz TA,Rucci Gsubject
Has Abstractpub_date
1984-07-01 00:00:00pages
90-8issue
1eissn
0026-895Xissn
1521-0111journal_volume
26pub_type
杂志文章abstract::Identifying novel mechanisms to enhance glucagon-like peptide-1 (GLP-1) receptor signaling may enable nascent medicinal chemistry strategies with the aim of developing new orally available therapeutic agents for the treatment of type 2 diabetes mellitus. Therefore, we tested the hypothesis that selectively modulating ...
journal_title:Molecular pharmacology
pub_type: 杂志文章
doi:10.1124/mol.112.080432
更新日期:2012-12-01 00:00:00
abstract::One-electron oxidation of several derivatives of pyrazolin-5-one, including the drug antipyrine, were studied by pulse radiolysis of aqueous solutions. All the compounds were found to be oxidized by Br2 rapidly (k approximately 3 X 10(8)-2 X 10(9) M-1 s-1) but considerably more slowly by weaker oxidants, such as perox...
journal_title:Molecular pharmacology
pub_type: 杂志文章
doi:
更新日期:1985-10-01 00:00:00
abstract::Bovine pulmonary artery endothelial (CPAE) cells respond to bradykinin, and it has been suggested that the receptors on these cells do not fall into the normal B1/B2 classification of bradykinin receptors [J. Pharmacol. Exp. Ther. 244:646-649 (1988)]. The present study describes a detailed characterization of the subt...
journal_title:Molecular pharmacology
pub_type: 杂志文章
doi:
更新日期:1995-03-01 00:00:00
abstract::We investigated the roles of cyclic GMP and cyclic AMP in the inhibition of rabbit platelet aggregation and degranulation by two nitrovasodilators, sodium nitroprusside (SNP) and 3-morpholinosydnonimine (SIN-1; the active metabolite of molsidomine), with particular reference to the synergistic interaction of these dru...
journal_title:Molecular pharmacology
pub_type: 杂志文章
doi:
更新日期:1990-05-01 00:00:00
abstract::2,3,7,8-Tetrachlorodibenzo-p-dioxin (TCDD) was found to activate protein kinases under cell- and nucleus-free conditions in isolated C57 mouse liver cytosol (100,000 x g supernatant). This action of TCDD was found to be aryl hydrocarbon receptor (AHR) dependent, concentration dependent, and inhibited by genistein, a t...
journal_title:Molecular pharmacology
pub_type: 杂志文章
doi:10.1124/mol.52.4.667
更新日期:1997-10-01 00:00:00
abstract::Metabolism of the pulmonary toxin, 4-ipomeanol, in microsomal preparations from rabbit liver and lung and in purified cytochrome P-450-dependent monooxygenase systems was investigated. The rate of formation of reactive electrophilic products from 4-ipomeanol was estimated by measuring covalent binding to protein or gl...
journal_title:Molecular pharmacology
pub_type: 杂志文章
doi:
更新日期:1982-11-01 00:00:00
abstract::The interaction between two nonhomologous K+ channel toxins, Tityus serrulatus (scorpion) toxin tityustoxin-K alpha (TsTX-K alpha) and Dendroaspis angusticeps (snake) toxin dendrotoxin (alpha-DTX), was investigated on K+ currents in B82 fibroblast cells transformed to express the Kv1.2 K+ channel. As demonstrated prev...
journal_title:Molecular pharmacology
pub_type: 杂志文章
doi:
更新日期:1993-08-01 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 precise mechanism by which the broad-spectrum anti-RNA virus agent ribavirin elicits its in vitro antiviral effect has remained a matter of debate. We have demonstrated that inhibition of cellular inosine monophosphate dehydrogenase (IMPDH) activity, and thus depletion of intracellular GTP pools, is the predominan...
journal_title:Molecular pharmacology
pub_type: 杂志文章
doi:10.1124/mol.105.020057
更新日期:2006-04-01 00:00:00
abstract::Sulfation, catalyzed by members of the sulfotransferase (SULT) superfamily, exerts considerable influence over the biological activity of numerous endogenous and xenobiotic chemicals. In humans, catecholamines such as dopamine are extensively sulfated, and a SULT isoform (SULT1A3 or the monoamine-sulfating form of phe...
journal_title:Molecular pharmacology
pub_type: 杂志文章
doi:10.1124/mol.54.6.942
更新日期:1998-12-01 00:00:00
abstract::The relationship between receptor number and agonist-induced intracellular responses has been well studied in receptors coupled to adenylate cyclase; however, for receptors coupled to phospholipase C (PLC), very little is known about the effect of receptor number on receptor-mediated processes. To explore this issue, ...
journal_title:Molecular pharmacology
pub_type: 杂志文章
doi:10.1124/mol.51.5.721
更新日期:1997-05-01 00:00:00
abstract::Iron is a biologically essential metal, but excess iron can cause damage to the cardiovascular and nervous systems. We examined the effects of extracellular Fe²⁺ on permeation and gating of Ca(V)3.1 channels stably transfected in HEK293 cells, by using whole-cell recording. Precautions were taken to maintain iron in t...
journal_title:Molecular pharmacology
pub_type: 杂志文章
doi:10.1124/mol.112.080184
更新日期:2012-12-01 00:00:00
abstract::Upon sustained insult, kinins are released and many kinin responses, such as inflammatory pain, adapt from a B2 receptor (B2R) type in the acute phase to a B1 receptor (B1R) type in the chronic phase. In this study, we show that kinins modulate receptor endocytosis to rapidly decrease B2R and increase B1R on the cell ...
journal_title:Molecular pharmacology
pub_type: 杂志文章
doi:10.1124/mol.106.030858
更新日期:2007-02-01 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::G protein-coupled receptor kinases (GRKs) play a key role in the process of receptor homologous desensitization. In the present study, we address the question of whether a variety of receptors coupled to different G protein subtypes and naturally expressed on the same cell are selectively regulated by GRK2. The signal...
journal_title:Molecular pharmacology
pub_type: 杂志文章
doi:10.1124/mol.56.2.316
更新日期:1999-08-01 00:00:00
abstract::KARs, new semisynthetic antitumor bis-indole derivatives, were found to be inhibitors of tubulin polymerization with lower toxicity than vinblastine or vincristine, used in chemotherapy. Here, we compare the effect of KARs with those of vinblastine and vincristine on cell viability, cell proliferation, and cell cycle ...
journal_title:Molecular pharmacology
pub_type: 杂志文章
doi:10.1124/mol.60.6.1235
更新日期:2001-12-01 00:00:00
abstract::Arrestins mediate G protein-coupled receptor desensitization, internalization, and signaling. Dopamine D(2) and D(3) receptors have similar structures but distinct characteristics of interaction with arrestins. The goals of this study were to compare arrestin-binding determinants in D(2) and D(3) receptors other than ...
journal_title:Molecular pharmacology
pub_type: 杂志文章
doi:10.1124/mol.108.050534
更新日期:2009-01-01 00:00:00
abstract::Phosphodiesterase-9 (PDE9) inhibitors have been studied as potential therapeutics for treatment of central nervous system diseases and diabetes. Here, we report the discovery of a new category of PDE9 inhibitors by rational design on the basis of the crystal structures. The best compound, (S)-6-((1-(4-chlorophenyl)eth...
journal_title:Molecular pharmacology
pub_type: 杂志文章
doi:10.1124/mol.115.099747
更新日期:2015-11-01 00:00:00
abstract::Chick brain mRNA was isolated and injected into Xenopus oocytes. This led to the expression of gamma-aminobutyrate (GABA) channels easily accessible for current measurements using the voltage clamp technique. The effect of the anthelmintic natural product avermectin B1a on the GABA current was studied quantitatively. ...
journal_title:Molecular pharmacology
pub_type: 杂志文章
doi:
更新日期:1987-12-01 00:00:00
abstract::The phosphorylation of μ-opioid receptors (MOPRs) by G protein-coupled receptor kinases (GRKs), followed by arrestin binding, is thought to be a key pathway leading to desensitization and internalization. The present study used the combination of intracellular and whole-cell recordings from rats and mice, as well as l...
journal_title:Molecular pharmacology
pub_type: 杂志文章
doi:10.1124/mol.111.076208
更新日期:2012-03-01 00:00:00
abstract::The highly conserved Arg in the so-called DRY motif (Asp-Arg-Tyr) at the intracellular end of transmembrane helix 3 is in general considered as an essential residue for G protein coupling in rhodopsin-like seven transmembrane (7TM) receptors. In the open reading frame 74 (ORF74) receptor encoded by equine herpesvirus ...
journal_title:Molecular pharmacology
pub_type: 杂志文章
doi:10.1124/mol.105.011239
更新日期:2005-07-01 00:00:00
abstract::We have used two experimental approaches--receptor inactivation with an irreversible antagonist and changes in receptor expression during passage of cells through the cell cycle--to explore the relationship between beta-adrenergic receptor number and response in intact S49 lymphoma cells. beta-Receptors in asynchronou...
journal_title:Molecular pharmacology
pub_type: 杂志文章
doi:
更新日期:1986-01-01 00:00:00
abstract::Ca2-dependent protein phosphorylations activated by calmodulin or phospholipid were studied using selective inhibitors. Both protein phosphorylations were inhibited by N-(6-aminohexyl)-5-chloro-1-naphthalenesulfonamide (W-7) and its derivatives. Kinetic analysis indicated that the primary effect of these agents was me...
journal_title:Molecular pharmacology
pub_type: 杂志文章
doi:
更新日期:1982-09-01 00:00:00
abstract::We recently reported the cloning of a novel alpha 1-adrenergic receptor (AR), the alpha 1CAR. By transient and stable expression of the alpha 1CAR and the previously cloned alpha 1BAR in COS-7 and HeLa cells, respectively, we have now compared their ability to interact with major signal-transduction pathways (includin...
journal_title:Molecular pharmacology
pub_type: 杂志文章
doi:
更新日期:1991-11-01 00:00:00
abstract::Recent years have witnessed the discovery of novel selective agonists of the M(1) muscarinic acetylcholine (ACh) receptor (mAChR). One mechanism invoked to account for the selectivity of such agents is that they interact with allosteric sites. We investigated the molecular pharmacology of two such agonists, 1-[3-(4-bu...
journal_title:Molecular pharmacology
pub_type: 杂志文章
doi:10.1124/mol.110.064345
更新日期:2010-07-01 00:00:00
abstract::Reuptake of glutamate in astrocytes, a critical mechanism involved in the maintenance of physiological excitatory amino acid neurotransmission, is inhibited by both arachidonic acid (AA) and reactive oxygen species (ROS), via incompletely defined molecular mechanisms. Because ROS are generated during AA metabolism and...
journal_title:Molecular pharmacology
pub_type: 杂志文章
doi:
更新日期:1994-11-01 00:00:00
abstract::Polycyclic aromatic hydrocarbons (PAHs) are widely distributed environmental toxicants derived from sources that include cigarette smoke, petroleum distillation, gas- and diesel-engine exhaust, and charcoal-grilled food. The gastrointestinal tract is the principal route of PAH exposures, even when inhaled. The most th...
journal_title:Molecular pharmacology
pub_type: 杂志文章
doi:10.1124/mol.110.063438
更新日期:2010-07-01 00:00:00
abstract::The dopamine D3 receptor, although structurally similar to the dopamine D2 receptor, has 100-fold higher affinity for agonists such as dopamine and quinpirole, when these receptors are expressed in 293 cells. Additionally, the D3 receptor has generally lower affinity for several antagonists than does the D2 receptor. ...
journal_title:Molecular pharmacology
pub_type: 杂志文章
doi:
更新日期:1994-08-01 00:00:00
abstract::The level of cellular ceramide, an apoptotic rheostat, is increased by sphingomyelinase or de novo synthesis. The expression of the glutathione S-transferase (GST) gene, whose induction accounts for cell viability, is regulated by activation of CCAAT/enhancer binding protein-beta (C/EBPbeta) and NF-E2-related factor-2...
journal_title:Molecular pharmacology
pub_type: 杂志文章
doi:10.1124/mol.65.6.1475
更新日期:2004-06-01 00:00:00
abstract::The new olivacine derivative S16020-2 (NSC-659687) is a DNA topoisomerase II inhibitor endowed with a remarkable antitumor activity against various experimental tumors. In vitro physicochemical properties of this compound, in particular its interaction with DNA and DNA topoisomerase II, were very similar to those of e...
journal_title:Molecular pharmacology
pub_type: 杂志文章
doi:10.1124/mol.58.4.709
更新日期:2000-10-01 00:00:00