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Blocking Effects (blocking + effects)
Selected AbstractsPotentiation of glycine responses by dideoxyforskolin and tamoxifen in rat spinal neuronsEUROPEAN JOURNAL OF NEUROSCIENCE, Issue 4 2003Dominique Chesnoy-Marchais Abstract Dideoxyforskolin, a forskolin analogue unable to stimulate adenylate cyclase, and tamoxifen, an antioestrogen widely used against breast cancer, are both known to block some Cl, channels. Their effects on Cl, responses to glycine or GABA have been tested here by using whole-cell recording from cultured spinal neurons. Dideoxyforskolin (4 or 16 µm) and tamoxifen (0.2,5 µm) both potentiate responses to low glycine concentrations. They also induce blocking effects, predominant at high glycine concentrations. At 5 µm, tamoxifen increased responses to 15 µm glycine by a factor >4.5, reaching 20 in some neurons. Potentiation by extracellular dideoxyforskolin or tamoxifen persisted after intracellular application of the modulator and was not due to Zn2+ contamination. Potentiation by tamoxifen also persisted in a Ca2+ -free extracellular solution, after intracellular Ca2+ buffering and protein kinase C blockade. Thus, the critical sites of action are not intracellular. The EC50 for glycine was lowered 6.6-fold by 5 µm tamoxifen. The kinetics and voltage-dependence of the effects of tamoxifen on glycine responses support the idea that this hydrophobic drug may act from a site located within the membrane. Tamoxifen (5 µm) also increased responses to 2 µm GABA by a factor of 3.5, but barely affected peak responses to 20 µm GABA. The demonstration that tamoxifen affects some of the main inhibitory receptors should be useful for better evaluating its neurological effects. Furthermore, the results identify a new class of molecules that potentiate glycine receptor function. [source] Modulation of glycine responses by dihydropyridines and verapamil in rat spinal neuronsEUROPEAN JOURNAL OF NEUROSCIENCE, Issue 12 2001Dominique Chesnoy-Marchais Abstract Although glycine receptors (GlyRs) are responsible for the main spinal inhibitory responses in adult vertebrates, in the embryo they have been reported to mediate depolarizing responses, which can sometimes activate dihydropyridine-sensitive l -type calcium channels. However, these channels are not the only targets of dihydropyridines (DHPs), and we questioned whether GlyRs might be directly modulated by DHPs. By whole-cell recording of cultured spinal neurons, we investigated modulation of glycine responses by the calcium channel antagonists, nifedipine, nitrendipine, nicardipine and (R)-Bay K 8644, and by the calcium channel, agonist (S)-Bay K 8644. At concentrations between 1 and 10 µm, all these DHPs could block glycine responses, even in the absence of extracellular Ca2+. The block was stronger at higher glycine concentrations, and increased with time during each glycine application. Nicardipine blocked GABAA responses from the same neurons in a similar manner. In addition to their blocking effects, nitrendipine and nicardipine potentiated the peak responses to low glycine concentrations. Both effects of extracellular nitrendipine on glycine responses persisted when the drug was present in the intracellular solution. Thus, these modulations are related neither to calcium channel modulation nor to possible intracellular effects of DHPs. Another type of calcium antagonist, verapamil (10,50 µm), also blocked glycine responses. Our results suggest that some of the effects of calcium antagonists, including the neuroprotective and anticonvulsant effects of DHPs, might result partly from their interactions with ligand-gated chloride channels. [source] Ethanol and Acetaldehyde Adsorption on a Carbon-Supported Pt Catalyst: A Comparative DEMS StudyFUEL CELLS, Issue 1-2 2004H. Wang Abstract The adsorption of ethanol and acetaldehyde on carbon Vulcan supported Pt fuel cell catalyst and the electrochemical desorption of the adsorption products were studied, using electrochemical measurements and differential electrochemical mass spectrosmetry (DEMS), under continuous flow conditions. Faradaic current adsorption transients at different constant adsorption potentials, which also include CO adsorption for comparison, show pronounced effects of the adsorption potential and the nature of the reactant molecule. Acetaldehyde adsorption is much faster than ethanol adsorption at all potentials. Pronounced Had induced blocking effects for ethanol adsorption are observed at very cathodic adsorption potentials, < 0.16,V, while for acetaldehyde adsorption this effect is much less significant. Comparison of the adsorption charge for CO adsorption with the H-upd charge allows differentiation between H-displacement and double-layer charging effects. Continuous bulk oxidation is observed for both reactants at potentials > 0.31,V; for acetaldehyde adsorption, increasing bulk reduction is found at low potentials. Based on the electron yield per CO2 molecule formed and on the similarity with the CO stripping characteristics the dominant stable adsorbate is CO, coadsorbed with smaller amounts of (partly oxidized) hydrocarbon decomposition fragments, which are also oxidized at higher potentials (> 0.85,V) and which can be reductively desorbed as methane or, to a very small extent, as ethane. The presence of small amounts of adsorbed C2 species and the oxidative dissociation of these species in the main CO oxidation potential range is clearly demonstrated by increased methane desorption after a potential shift to 0.85,V. The data demonstrate that the Pt/Vulcan catalyst is very reactive for C-C bond breaking upon adsorption of these reactants. [source] Cigarette smoke extract affects functional activity of MRP1 in bronchial epithelial cellsJOURNAL OF BIOCHEMICAL AND MOLECULAR TOXICOLOGY, Issue 5 2007Margaretha van der Deen Abstract Cigarette smoke is the principal risk factor for development of chronic obstructive pulmonary disease (COPD). Multidrug resistance-associated protein 1 (MRP1) is a member of the ATP-binding cassette (ABC) superfamily of transporters, which transport physiologic and toxic substrates across cell membranes. MRP1 is highly expressed in lung epithelium. This study aims to analyze the effect of cigarette smoke extract (CSE) on MRP1 activity. In the human bronchial epithelial cell line 16HBE14o,, MRP1 function was studied flow cytometrically by cellular retention of carboxyfluorescein (CF) after CSE incubation and MRP1 downregulation by RNA interference (siRNA). Cell survival was measured by the MTT assay. Immunocytochemically, it was shown that 16HBE14o, expressed MRP1 and breast cancer resistance protein. Coincubation of CSE IC50 (1.53% ± 0.22%) with MK571 further decreased cell survival 31% (p, = 0.018). CSE increased cellular CF retention dose dependently from 1.7-fold at 5% CSE to 10.3-fold at 40% CSE (both p < 0.05). siRNA reduced MRP1 RNA expression with 49% and increased CF accumulation 67% versus control transfected cells. CSE exposure further increased CF retention 24% (p = 0.031). A linear positive relation between MRP1 function and CSE-modulating effects (r = 0.99, p =0.089) was shown in untransfected, control transfected, and MRP1 downregulated 16HBE14o, cells analogous to blocking effects with MRP1 inhibitor MK571 (r = 0.99, p = 0.034). In conclusion, cigarette smoke extract affects MRP1 activity probably competitively in bronchial epithelial cells. Inhibition of MRP1 in turn results in higher CSE toxicity. We propose that MRP1 may be a protective protein for COPD development. © 2007 Wiley Periodicals, Inc. J Biochem Mol Toxicol 21:243,251, 2007; Published online in Wiley InterScience (www.interscience.wiley.com). DOI 10.1002/jbt.20187 [source] Anti-inflammatory properties of local anesthetics and their present and potential clinical implicationsACTA ANAESTHESIOLOGICA SCANDINAVICA, Issue 3 2006J. Cassuto Development of new local anesthetic agents has been focused on the potency of their nerve-blocking effects, duration of action and safety and has resulted in a substantial number of agents in clinical use. It is well established and well documented that the nerve blocking effects of local anesthetics are secondary to their interaction with the Na+ channels thereby blocking nerve membrane excitability and the generation of action potentials. Accumulating data suggest however that local anesthetics also posses a wide range of anti-inflammatory actions through their effects on cells of the immune system, as well as on other cells, e.g. microorganisms, thrombocytes and erythrocytes. The potent anti-inflammatory properties of local anesthetics, superior in several aspects to traditional anti-inflammatory agents of the NSAID and steroid groups and with fewer side-effects, has prompted clinicians to introduce them in the treatment of various inflammation-related conditions and diseases. They have proved successful in the treatment of burn injuries, interstitial cystitis, ulcerative proctitis, arthritis and herpes simplex infections. The detailed mechanisms of action are not fully understood but seem to involve a reversible interaction with membrane proteins and lipids thus regulating cell metabolic activity, migration, exocytosis and phagocytosis. [source] Electrophysiologic Effects of Carvedilol: Is Carvedilol an Antiarrhythmic Agent?PACING AND CLINICAL ELECTROPHYSIOLOGY, Issue 9 2005NABIL EL-SHERIF The cardiovascular drug carvedilol is characterized by multiple pharmacological actions, which translate into a wide-spectrum therapeutic potential. Its major molecular targets are membrane adrenoceptors, ion channels, and reactive oxygen species. Carvedilol's favorable hemodynamic effects are due to the fact that the drug competitively blocks ,1 -, ,2 -, and ,1 - adrenoceptors. Several additional properties have been documented and may be clinically important, including antioxidant, antiproliferative/antiatherogenic, anti-ischemic, and antihypertrophic effects. The antiarrhythmic action of carvedilol may be related to a combination of its ,-blocking effects with its modulating effects on a variety of ion channels and currents. Several studies suggest that the drug may be useful in reducing cardiac death in high-risk patients with prior myocardial infarction and/or heart failure, as well as for primary and secondary prevention of atrial fibrillation. This article will review experimental data available on the electrophysiologic properties of carvedilol, with a focus on their clinical relevance. [source] Photon statistics of a single quantum dot in a microcavityPHYSICA STATUS SOLIDI - RAPID RESEARCH LETTERS, Issue 10 2010Yumian Su Abstract We introduce a theoretical model to describe the dynamics of an electrically pumped single quantum dot interacting with a microcavity. Within our framework, it is possible to study the full photon statistics of the quantum light emission for different pump rates and to include semiconductor specific Pauli- blocking effects in the polarization dynamics. In the single photon limit, we find that, compared to comparable atomic systems, two photon events are suppressed stronger by the carrier reservoir of the quantum dot. (© 2010 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim) [source] A Review of HNS-32: A Novel Azulene-l-Carboxamidine Derivative with Multiple Cardiovascular Protective ActionsCARDIOVASCULAR THERAPEUTICS, Issue 4 2001Yoshio Tanaka ABSTRACT HNS-32 [N1,N1 -dimethyl- N2 -(2-pyridylmethyl)-5-isopropyl-3,8-dimethylazulene-1-carboxamidine] (CAS Registry Number: 186086-10-2) is a newly synthesized azulene derivative. Computer simulation showed that its three dimensional structure is similar to that of the class Ib antiarrhythmic drugs, e.g., lidocaine or mexiletine. HNS-32 potently suppressed ventricular arrhythmias induced by ischemia due to coronary ligation and/or ischemia-reperfusion in dogs and rats. In the isolated dog and guinea pig cardiac tissues, HNS-32 had negative inotropic and chronotropic actions, prolonged atrial-His and His-ventricular conduction time and increased coronary blood flow. In the isolated guinea pig ventricular papillary muscle, HNS-32 decreased maximal rate of action potential upstroke (V,max) and shortened action potential duration (APD). These findings suggest that HNS-32 inhibits inward Na+ and Ca2+ channel currents. In the isolated pig coronary and rabbit conduit arteries, HNS-32 inhibited both Ca2+ channel-dependent and -independent contractions induced by a wide variety of chemical stimuli. HNS-32 is a potent inhibitor of protein kinase C (PKC)-mediated constriction of cerebral arteries. It is likely to block both, Na+ and Ca2+ channels expressed in cardiac and vascular smooth muscles. These multiple ion channel blocking effects are largely responsible for the antiarrhythmic and vasorelaxant actions of HNS-32. This drug may represent a novel approach to the treatment of arrhythmias. [source] | |||||||||||||