Search results for "terase"
showing 10 items of 446 documents
Allosteric modulation of nicotinic acetylcholine receptors as a treatment strategy for Alzheimer's disease
2000
The basic symptoms of Alzheimer's dementia, i.e., a loss in cognitive function, are due to impaired nicotinic cholinergic neurotransmission. To compensate for this impairment by drug treatment, blockers of the acetylcholine-degrading enzyme acetylcholinesterase are applied, even though this approach obviously is prone to many side-effects, including those of muscarinic nature. We have recently described a novel class of nicotinic acetylcholine receptor ligands which, similar to the action of benzodiazepines on GABA(A) receptors, allosterically potentiate submaximal nicotinic responses. The sensitizing effect is a consequence of facilitated channel opening in the presence of allosterically p…
1-Naphthyl Acetate-Dependent Medium Acidification by Zea mays L. Coleoptile Segments
1991
Zea mays L. cv INRA 5a coleoptile segments ecidify the incubation medium on the addition of 1-naphthyl acetate (1-NA). The buffering capacity of the bathing solution increases during 1-NA stimulated medium acidification. The solution bathing the 1-NA treated coleoptile segment was analyzed by high performance liquid chromatography. A considerable amount of acetic acid was detected in the bathing solution used to measure 1-NA-dependent medium acidification. For the first time, the data demonstrate directly the release of acetic acid from 1-NA. The extent of medium acidification was proportional to 1-NA concentration. Simultaneous measurement of medium acidification and acetate content upon a…
Screening of acetylcholinesterase inhibitors by CE after enzymatic reaction at capillary inlet.
2009
In this study the development of a procedure based on capillary electrophoresis after enzymatic reaction at capillary inlet methodology for the screening and in vitro evaluation of the biological activity of acetylcholinesterase (AChE) inhibitors is presented. The progress of the enzymatic reaction of the hydrolysis of acetylthiocholine at pH 8 in the presence of AChE and the inhibitor studied is determined by measuring at 230 nm the peak area of the reaction product thiocholine (TCh). In the method employed the capillary was first filled with 30 mM borate-phosphate buffer (pH 8.0) and subsequently, plugs of: (i) water, (ii) AChE solution, (iii) substrate solution with or without inhibitor,…
Effects of the Phosphodiesterase Inhibitor Enoximone on the Autonomic Innervation of the Isolated Heart
1989
Enoximone is a selective inhibitor of a low Km, cyclic AMP-specific type of phosphodiesterase (PDE III). In guinea pig and chicken atria, enoximone (0.1-100 mumol/L) caused a weak increase in the force of contraction. The heart rate was slightly enhanced or was unchanged (chicken). Enoximone (30 mumol/L) also failed to shift the concentration-response curves for the positive inotropic and chronotropic effects of norepinephrine in guinea pig atria. Under almost the same conditions, enoximone and the nonselective PDE inhibitor 3-isobutyl-1-methylxanthine (IBMX) markedly potentiated the forskolin-induced mobilization of choline from phospholipids. The concentrations of IBMX (100 mumol/L) and o…
Reliability of Virtual Screening Methods in Prediction of PDE4Binhibitor Activity
2015
Identification of active ligands using computational methods is a challenging task. For example, molecular docking, pharmacophore modeling, and three dimensional quantitative structure-activity relationship models (3D-QSAR) are widely used methods to identify novel small molecules. However, all these methods have, in addition to advantages, also significant pitfalls. The aim of this study was to compare some commonly used computational methods to estimate their ability to separate highly active PDE4B-inhibitors from less active and inactive ones. Here, 152 molecules with pIC 50 -range of 3.4-10.5, originating from six original studies were used. High correlation coefficients by using dockin…
Effects of SCA40 on human isolated bronchus and human polymorphonuclear leukocytes: comparison with rolipram, SKF94120 and levcromakalim
1996
1. SCA40 (0.1 nM-0.1 mM) produced concentration-dependent suppression of the spontaneous tone of human isolated bronchus (-log EC50 = 6.85 +/- 0.09; n = 10) and reached a maximal relaxation similar to that of theophylline (3 mM). The potency (-log EC50 values) of SCA40 compared to other relaxants was rolipram (7.44 +/- 0.12; n = 9) > SCA40 > or = levcromakalim (6.49 +/- 0.04; n = 6) > SKF94120 (5.87 +/- 0.10; n = 9). 2. When tested against the activity of the isoenzymes of cyclic nucleotide phosphodiesterase (PDE) isolated from human bronchus, SCA40 proved highly potent against PDE III (-log IC50 = 6.47 +/- 0.16; n = 4). It was markedly less potent against PDE IV (4.82 +/- 0.18; n = 4) and …
Role of curcumin in idiopathic pulmonary arterial hypertension treatment: A new therapeutic possibility
2013
The idiopathic pulmonary arterial hypertension is a complex disease that mainly affects pulmonary arterial circulation. This undergoes a remodeling with subsequent reduction of flow in the small pulmonary arteries. Because of this damage an increased vascular resistance gradually develops, and over time it carries out in heart failure. The inflammatory process is a key element in this condition, mediated by various cytokines. The inflammatory signal induces activation of NF-κB, and prompts TGF-β-related signaling pathway. Clinical evolution leads to progressive debilitation, greatly affecting the patient quality of life. The actual therapeutic approaches, are few and expensive, and include …
Comparison of virtual high-throughput screening methods for the identification of phosphodiesterase-5 inhibitors.
2011
Reliable and effective virtual high-throughput screening (vHTS) methods are desperately needed to minimize the expenses involved in drug discovery projects. Here, we present an improvement to the negative image-based (NIB) screening: the shape, the electrostatics, and the solvation state of the target protein’s ligand-binding site are included into the vHTS. Additionally, the initial vHTS results are postprocessed with molecular mechanics/generalized Born surface area (MMGBSA) calculations to estimate the favorability of ligand-protein interactions. The results show that docking produces very good early enrichment for phosphodiesterase-5 (PDE-5); however, in general, the NIB and the ligand-…
The phosphodiesterase 4 inhibitor roflumilast augments the Th17-promoting capability of dendritic cells by enhancing IL-23 production, and impairs th…
2016
Phosphodiesterase 4 (PDE4) inhibitors serve to prevent degradation of the intracellular second messenger cAMP, resulting in broad anti-inflammatory effects on different cell types including immune cells. Agents that elevate cAMP levels via activation of adenylate cyclase have been shown to imprint a Th17-promoting capacity in dendritic cells (DCs). Therefore, we studied the potential of therapeutically relevant PDE inhibitors to induce a pronounced Th17-skewing capacity in DCs. Here we show that mouse bone marrow-derived (BM-) DCs when treated with the PDE4 inhibitor roflumilast (ROF, trade name: Daxas) in the course of stimulation with LPS (ROF-DCs) evoked elevated IL-17 levels in cocultur…
PDE4 inhibitors as new anti-inflammatory drugs: effects on cell trafficking and cell adhesion molecules expression.
2004
Phosphodiesterase 4 (PDE4) is a major cyclic AMP-hydrolyzing enzyme in inflammatory and immunomodulatory cells. The wide range of inflammatory mechanisms under control by PDE4 points to this isoenzyme as an attractive target for new anti-inflammatory drugs. Selective inhibitors of PDE4 have demonstrated a broad spectrum of anti-inflammatory activities including the inhibition of cellular trafficking and microvascular leakage, cytokine and chemokine release from inflammatory cells, reactive oxygen species production, and cell adhesion molecule expression in a variety of in vitro and in vivo experimental models. The initially detected side effects, mainly nausea and emesis, appear at least pa…