Search results for "binding site"
showing 10 items of 856 documents
Regulation of α4β2α5 nicotinic acetylcholinergic receptors in rat cerebral cortex in early and late adolescence: Sex differences in response to chron…
2013
Chronic nicotine administration in animals, and smoking in humans, causes up-regulation of α4β2* neuronal nicotinic receptors (nAChRs), which has been hypothesized to contribute to the addictive actions of nicotine. We used a rat model to test whether such up-regulatory effects differ in adolescents versus adults, and in males versus females. Following chronic treatment with nicotine or saline via subcutaneous osmotic minipumps, we measured α4β2 and α4β2α5 nAChRs in cerebral cortex using [3H]epibatidine to label assembled nAChRs, and selective antibodies to measure the individual subunits via immunoprecipitation. For the first time, we provide a detailed characterization of the response of …
Differential effect of insulin and epidermal growth factor on the mRNA translocation system and transport of specific poly(A+) mRNA and poly(A-) mRNA…
1990
The efficiency of efflux of rapidly labeled poly(A)-containing mRNA from isolated rat liver nuclei was found to be modulated by insulin and epidermal growth factor (EGF) in a biphasic but opposite way. At physiological concentrations (10 pM insulin and 1 pM EGF), maximal stimulation of the transport rate by insulin (to 137%) and maximal inhibition by EGF (to 69%) were obtained; at higher concentrations (greater than 100 pM and greater than 10 pM, respectively), the amount of poly(A)-containing mRNA released into the postnuclear supernatant was nearly identical with the level found in untreated nuclei (= 100%). Using mRNA entrapped into closed nuclear envelope (NE) vesicles as a model system…
Prognostic role of the LCS6 KRAS variant in locally advanced rectal cancer: results of the EXPERT-C trial
2015
KRAS mutation has been reported as a marker of radio-resistance in rectal cancer and unfavourable outcome in both colon and rectal cancer. This study suggests that a single-nucleotide polymorphism of the KRAS gene (LCS-6 variant) may predict response to neoadjuvant treatment and mitigate the poor prognosis associated with KRAS mutation in locally advanced rectal cancer.
Pregnane X receptor and yin yang 1 contribute to the differential tissue expression and induction of CYP3A5 and CYP3A4.
2012
The hepato-intestinal induction of the detoxifying enzymes CYP3A4 and CYP3A5 by the xenosensing pregnane X receptor (PXR) constitutes a key adaptive response to oral drugs and dietary xenobiotics. In contrast to CYP3A4, CYP3A5 is additionally expressed in several, mostly steroidogenic organs, which creates potential for induction-driven disturbances of the steroid homeostasis. Using cell lines and mice transgenic for a CYP3A5 promoter we demonstrate that the CYP3A5 expression in these organs is non-inducible and independent from PXR. Instead, it is enabled by the loss of a suppressing yin yang 1 (YY1)-binding site from the CYP3A5 promoter which occurred in haplorrhine primates. This YY1 sit…
Lateral differences in the GABAergic system of the rat striatum.
1985
Asymmetric differences have been found in the pre- and postsynaptic activity of the GABAergic system of the left and right striata of the rat. 3H-GABA binding shows a higher dissociation constant (KD) and a higher number of sites (Bmax) in the left striatum than in the right. Moreover, 3H-diazepam binding seems to be more extensively activated by GABA in the right striatum suggesting a more sensitive postsynaptic GABAergic activity than on the left side. However, when the presynaptic marker (GAD activity) was measured, the asymmetry was in the opposite direction. The results provide further neurochemical evidence of the functional asymmetry of the rat brain.
The 3,4-oxide is responsible for the DNA binding of benzo[ghi]perylene, a polycyclic aromatic hydrocarbon without a “classic” bay-region
2008
Abstract The polycyclic aromatic hydrocarbon (PAH) benzo[ghi]perylene (BghiP) lacks a “classic” bay-region and is therefore unable to form vicinal dihydrodiol epoxides thought to be responsible for the genotoxicity of carcinogenic PAHs like benzo[a]pyrene. The bacterial mutagenicity of BghiP increases considerably after inhibition of the microsomal epoxide hydrolase (mEH) indicating arene oxides as genotoxic metabolites. Two K-region epoxides of BghiP, 3,4-epoxy-3,4-dihydro-BghiP (3,4-oxide) and 3,4,11,12-bisepoxy-3,4,11,12-tetrahydro-BghiP (3,4,11,12-bisoxide) identified in microsomal incubations of BghiP are weak bacterial mutagens in strain TA98 of Salmonella typhimurium with 5.5 and 1.5…
Identification and properties of the cell membrane bound leucine aminopeptidase interacting with the potential immunostimulant and chemotherapeutic a…
1983
Bestatin was found to be a competitive inhibitor (with respect to the Leu-NA substrate) not only of the isolated microsomal and cytosolic leucine aminopeptidases (Leu-APm and Leu-APc) but also of the aminopeptidases (APs) present in membrane preparations (from mouse liver) and on the cell surface of L5178Y cells. Kinetic parameters indicate that cellular AP is identical to Leu-APm. To rule out the possibility that AP-B is involved in the inhibition reactions, comparable studies with amastatin were performed. Electrophoretical studies revealed the solubilized cell membrane bound AP to co-migrate with Leu-APm in polyacrylamide gels. The activity of the separated membrane AP was inhibited by b…
Specificity of H-2-linked Ir gene control in mice: recognition of the core structure A--L in defined sequence analogues of (T,G,)-A--L.
1979
For further characterization of the processes involved in Ir gene control, the specificity of antibodies and the cross-reaction on the level of helper T cells was studied for a series of polypeptide antigens related to poly-L(Tyr,Glu)-poly-DL-Ala–poly-LLys[(T,G)-A–L] but carrying more defined side chains. Helper cell specificity was assayed in an in vitro secondary anti-dinitrophenyl (DNP) response by cross-stimulation of primed T cells with the various polypeptide carriers. It was established that these polypeptides, although showing the same response pattern, were recognized as distinct entities in the immune response by B and T cells. If this common pattern is due to the effect of the sa…
Effects of anti-cardiolipin antibodies and IVIg on annexin A5 binding to endothelial cells: implications for cardiovascular disease
2010
Anti-phospholipid antibodies (aPL), including anti-cardiolipin antibodies (aCL), are risk factors for cardiovascular disease (CVD) in the general population and in patients with the anti-phospholipid syndrome (APS; Hughes syndrome). APS may be primary but is also common in patients with systemic lupus erythematosus (SLE). The anti-coagulant protein annexin A5 (ANXA5) is implicated in CVD by interfering with phospholipids and aPL.ANXA5 binding to human umbilical venous endothelial cells (HUVECs) was determined by flow cytometry.When cells were cultured in serum from APS patients with a high aPL titre (aPL-S), binding of ANXA5 to HUVECs was reduced. Monoclonal immunoglobulin (Ig)G aPL against…
Characterization of a Ryanodine Receptor inPeriplaneta Americana
1997
Specific binding sites for the alkaloid ryanodine were characterized in membrane preparations from sarcoplasmatic reticulum of Periplaneta americana skeletal muscle. Binding of [3H]ryanodine was optimal at pH 8 and at CaCl2 concentration of about 300 mumol l-1. The Ca-chelating agents EGTA (100 mumol l-1) and EDTA (100 mumol l-1) abolished 95% and 90% of the [3H]ryanodine binding respectively. Preincubation with Ca2+ (100 mumol l-1) restored the ryanodine binding in presence of up to 300 mumol l-1 EGTA. Radioligand binding experiments showed one class of high affinity binding sites for ryanodine. Determination of rate constants revealed 7.05 x 10(6) l mol-1 min-1 for associating and 3.77 x …