Abstract:
:GABAA receptors are ligand-gated ion channels that form a fundamental component of inhibitory neurotransmission in the central and peripheral nervous systems. However, since the initial recordings of inhibitory electrical activity of neurons in response to GABA, these receptors have been found to play a more complex role and can, under some circumstances, function in an excitatory manner. This has been demonstrated via electrophysiological recordings conducted in both mature and developing neurons from different brain regions, as well as in various subcellular locations such as dendritic and axonal membranes. The balance between the inhibitory and excitatory effects mediated by GABAA receptor activation depends not only on multiple factors that govern the equilibrium of the transmembrane chloride gradient, but also on bicarbonate concentration. Moreover, electrophysiological and fluorescence measurements have revealed that a spatial distribution of the chloride gradient exists within neurons, which locally influences the effects mediated by GABAA receptor activation. In recent years, it has also become apparent that intra-neuronal chloride concentration is partially regulated by cation-chloride co-transporters (CCCs), in particular NKCC1 and KCC2. The aim of the present commentary is to discuss, in light of the latest findings, potential implications of the tight spatial and temporal regulation of chloride equilibrium in health and disease, as well as its relevance for the therapeutic effects of molecules acting at GABAA receptors.
journal_name
Biochem Pharmacoljournal_title
Biochemical pharmacologyauthors
Knoflach F,Hernandez MC,Bertrand Ddoi
10.1016/j.bcp.2016.03.014subject
Has Abstractpub_date
2016-09-01 00:00:00pages
10-7eissn
0006-2952issn
1873-2968pii
S0006-2952(16)00181-7journal_volume
115pub_type
杂志文章abstract::ABT-263 induces MCL1 upregulation in cancer cells, which confers resistance to the drug. An increased understanding of the mechanism underlying ABT-263-induced MCL1 expression may provide a strategy to improve its tumor-suppression activity. The present study revealed that ABT-263 reduced the turnover of MCL1 mRNA, th...
journal_title:Biochemical pharmacology
pub_type: 杂志文章
doi:10.1016/j.bcp.2020.114047
更新日期:2020-08-01 00:00:00
abstract::The effect of 2-(2,5-dimethoxyphenylmethyl)-3-(2-dimethylaminoethyl)- 6-isopropoxy-4(3H)-quinazolinone hydrochloride (MCI-176), a calcium antagonist, on ischemic myocardial metabolism was studied in dog hearts subjected to an occlusion of the left anterior descending coronary artery (LAD) for 3 or 30 min. MCI-176 (0.0...
journal_title:Biochemical pharmacology
pub_type: 杂志文章
doi:10.1016/0006-2952(91)90543-e
更新日期:1991-02-01 00:00:00
abstract::Characteristics of erythromycin binding to Staphylococcus aureus were determined by using kinetics and equilibrium binding experiments. Both methods yielded identical values of the dissociation constant, i.e. 0.1 muM. This value was in accord with that found with a bacterial extract of ribosomes which are the organell...
journal_title:Biochemical pharmacology
pub_type: 杂志文章
doi:10.1016/0006-2952(86)90090-0
更新日期:1986-03-15 00:00:00
abstract::The effect of the antianginal drug bepridil on Ca(2+) signaling in Madin-Darby canine kidney (MDCK) cells was investigated by using fura-2 as a Ca(2+) probe. Bepridil at 10-50 microM evoked a significant rise in cytosolic free Ca(2+) concentration ([Ca(2+)](i)) in a dose-dependent manner. The [Ca(2+)](i) rise consiste...
journal_title:Biochemical pharmacology
pub_type: 杂志文章
doi:10.1016/s0006-2952(99)00361-5
更新日期:2000-03-15 00:00:00
abstract::AM404 is a synthetic TRPV1/CB(1) hybrid ligand with inhibitory activity on the anandamide transporter and is used for the pharmacological manipulation of the endocannabinoid system. It has been recently described that acetaminophen is metabolised in the brain to form the bioactive N-acylphenolamine AM404 and therefore...
journal_title:Biochemical pharmacology
pub_type: 杂志文章
doi:10.1016/j.bcp.2006.12.001
更新日期:2007-04-01 00:00:00
abstract::Macrophages are key inflammatory cells in chronic obstructive pulmonary disease (COPD). The pathophysiology of cigarette smoke-induced lung emphysema is complex but there is a clear role for reactive oxygen species (ROS, such as peroxynitrite), tumor necrosis factor (TNF-alpha) and interleukin (IL)-8. We investigated ...
journal_title:Biochemical pharmacology
pub_type: 杂志文章
doi:10.1016/j.bcp.2009.10.001
更新日期:2010-03-01 00:00:00
abstract::We examined the effects of pyrazoloacridine (PZA), an investigational anticancer agent in clinical trials, on cytotoxicity, DNA synthesis, and DNA damage in MCF-7 human breast carcinoma cells. With PZA concentrations ranging from 0.5 to 50 microM for durations of 3-72 hr, cytotoxicity increased in proportion to the to...
journal_title:Biochemical pharmacology
pub_type: 杂志文章
doi:10.1016/0006-2952(96)00130-x
更新日期:1996-06-28 00:00:00
abstract::Inhibitory effects of Delta(9)-tetrahydrocannabinol (Delta(9)-THC), cannabidiol (CBD), and cannabinol (CBN), the three major constituents in marijuana, on catalytic activities of human cytochrome P450 (CYP) 1 enzymes were investigated. These cannabinoids inhibited 7-ethoxyresorufin O-deethylase activity of recombinant...
journal_title:Biochemical pharmacology
pub_type: 杂志文章
doi:10.1016/j.bcp.2010.01.028
更新日期:2010-06-01 00:00:00
abstract::Catalase, superoxide dismutase, and dimethylsulfoxide were tested for their ability to prevent the cytotoxic effect of 6-hydroxydopamine (6-OHDA) on the human neuroblastoma line SY5Y. Viability was measured at two time points after 6-OHDA treatment: at 3 hr by means of amino acid incorporation and at 24 hr by trypan b...
journal_title:Biochemical pharmacology
pub_type: 杂志文章
doi:10.1016/0006-2952(82)90208-8
更新日期:1982-01-15 00:00:00
abstract::Previously we reported that liposomal cisplatin (CDDP) overcomes CDDP resistance of ovarian A2780cis cancer cells (Krieger et al., Int. J. Pharm. 389, 2010, 10-17). Here we find that the cytotoxic activity of liposomal CDDP is not associated with detectable DNA platination in resistant ovarian cancer cells. This sugge...
journal_title:Biochemical pharmacology
pub_type: 杂志文章
doi:10.1016/j.bcp.2013.01.028
更新日期:2013-04-15 00:00:00
abstract:BACKGROUND/AIMS:Carnitine palmitoyl-transferase I (CPT I) catalyses the synthesis of long-chain (LC)-acylcarnitines from LC-acyl-CoA esters. It is the rate-limiting enzyme of mitochondrial fatty acid beta-oxidation (FAO) pathway and its activity is regulated by malonyl-CoA. The antiepileptic drug valproic acid (VPA) is...
journal_title:Biochemical pharmacology
pub_type: 杂志文章
doi:10.1016/j.bcp.2009.10.011
更新日期:2010-03-01 00:00:00
abstract::The increasing incidence of severe liver diseases worldwide has resulted in a high demand for curative liver transplantation. Unfortunately, the need for transplants by far eclipses the availability of suitable grafts leaving many waitlisted patients to face liver failure and often death. Routine use of smaller grafts...
journal_title:Biochemical pharmacology
pub_type: 杂志文章,评审
doi:10.1016/j.bcp.2020.113847
更新日期:2020-05-01 00:00:00
abstract::AKT1 (c-AKT, PKBalpha) is the cellular homolog of the protein-serine/threonine kinase oncogene, v-akt. AKT1 is activated through the insulin and platelet-derived growth factor signaling pathways in transfected fibroblasts, but little is known about the regulation of endogenous AKT1 in tumor cells. AKT1 levels were hig...
journal_title:Biochemical pharmacology
pub_type: 杂志文章
doi:10.1016/s0006-2952(99)00125-2
更新日期:1999-08-01 00:00:00
abstract::The aryl hydrocarbon receptor (AhR) is a ligand-activated transcription factor and member of the bHLH/PAS (basic Helix-Loop-Helix/Per-Arnt-Sim) family of chemosensors and developmental regulators. It represents a multifunctional molecular switch regulating endo- and xenobiotic metabolism as well as cell proliferation ...
journal_title:Biochemical pharmacology
pub_type: 杂志文章,评审
doi:10.1016/j.bcp.2006.01.017
更新日期:2006-08-14 00:00:00
abstract::Anti-idiotypic antibodies which recognize the opiate receptor were generated in guinea pigs following immunization against purified rabbit anti-morphine antibodies. The anti-idiotypic antibodies produced a concentration-dependent inhibition of [3H]naloxone binding to opiate receptors in a membranous mouse brain prepar...
journal_title:Biochemical pharmacology
pub_type: 杂志文章
doi:10.1016/0006-2952(85)90006-1
更新日期:1985-08-15 00:00:00
abstract::Double-labelled [methyl-14C,5-3H]CDPcholine has been synthesized and subjected to a pharmacokinetic analysis in several biological systems. In transport experiments with intact human erythrocytes no incorporation of radioactivity is observable. On the other hand the results obtained with perfused rat liver suggest a r...
journal_title:Biochemical pharmacology
pub_type: 杂志文章
doi:10.1016/0006-2952(85)90204-7
更新日期:1985-12-01 00:00:00
abstract::The aim of this study was to test if human platelet leukotriene C4-synthase (LTC4-S) is pharmacologically different from cloned and expressed LTC4-S and, in light of the significant homologies between 5-lipoxygenase activating protein (FLAP) and LTC4-S, if different potencies of leukotriene synthesis inhibitors acting...
journal_title:Biochemical pharmacology
pub_type: 杂志文章
doi:10.1016/s0006-2952(96)00819-2
更新日期:1997-03-21 00:00:00
abstract::In this study we investigated whether NADH fluorescence levels changed in response to low or high rates of electrical stimulation in single ventricular myocytes isolated from rat and guinea-pig hearts, either during a single contraction or upon sustained electrical stimulation of cells. NADH levels were determined fro...
journal_title:Biochemical pharmacology
pub_type: 杂志文章
doi:10.1016/s0006-2952(98)00016-1
更新日期:1998-07-15 00:00:00
abstract::Diethyl maleate (DEM) was given intraperitoneally to rats in a dose (4.3 mmoles/kg) known to markedly decrease glutathione levels in liver. DEM induced a choleresis previously shown to be due to the osmotic activity of DEM conjugates (DEM-glutathione and subsequent metabolic products) excreted into bile. Coincident wi...
journal_title:Biochemical pharmacology
pub_type: 杂志文章
doi:10.1016/0006-2952(82)90716-x
更新日期:1982-08-15 00:00:00
abstract::The oxidation of 14C-pyruvate by isolated rat pancreatic islets was inhibited competitively and in a concentration-dependent manner by alpha-cyano-4-hydroxycinnamate. A similar, though less marked inhibition was observed of U-14C-glucose oxidation, although oxidation of 1-14C-glucose was slightly enhanced in the prese...
journal_title:Biochemical pharmacology
pub_type: 杂志文章
doi:10.1016/0006-2952(88)90550-3
更新日期:1988-05-15 00:00:00
abstract::Improved syntheses, based on Lewis acid-catalyzed nucleosidation, are described for the preparation of 5-alkyl-2'-deoxyuridines. These were converted to their 5'-phosphates with the use of wheat shoot phosphotransferase. The dUMP analogues, 5-ethyl-dUMP and 5-propyl-dUMP, were competitive vs dUMP inhibitors of thymidy...
journal_title:Biochemical pharmacology
pub_type: 杂志文章
doi:10.1016/0006-2952(84)90683-x
更新日期:1984-09-01 00:00:00
abstract::We tested the influence of IFNgamma on proteasome activity in parental Hep G2 cells that do not metabolize ethanol, as well as in recombinant Hep G2-derived cells that express either or both alcohol dehydrogenase (ADH) and cytochrome P4502E1 (CYP2E1). IFNgamma treatment increased proteasome activity in VL-17A (ADH(+),...
journal_title:Biochemical pharmacology
pub_type: 杂志文章
doi:10.1016/s0006-2952(03)00252-1
更新日期:2003-09-01 00:00:00
abstract::The β2-adrenergic receptor (β2AR) is the prototypical member of the heptahelical G protein-coupled receptor (GPCR) superfamily and is well-known to elicit biological effects through both G protein-dependent and G protein-independent signaling cascades. Agonism of β2AR has been described to promote phosphorylation and ...
journal_title:Biochemical pharmacology
pub_type: 杂志文章
doi:10.1016/j.bcp.2012.06.012
更新日期:2012-09-01 00:00:00
abstract::Nitric oxide (NO) and hydrogen sulfide (H2S) are two gasotransmitters that are produced in the human body and have a key role in many of the physiological activities of the various organ systems. Decreased NO bioavailability and deficiency of H2S are involved in the pathophysiology of type 2 diabetes and its complicat...
journal_title:Biochemical pharmacology
pub_type: 杂志文章,评审
doi:10.1016/j.bcp.2020.113819
更新日期:2020-06-01 00:00:00
abstract::Arsenic, still a significant environmental threat in several regions in the world, induces various cancers, including lungs, skin, and bladder. Arsenic-induced Bowen's disease (As-BD) is generally an indolent cutaneous intraepithelial carcinoma in susceptible people. Patients with As-BD have been found to have attenua...
journal_title:Biochemical pharmacology
pub_type: 杂志文章
doi:10.1016/j.bcp.2012.01.028
更新日期:2012-05-01 00:00:00
abstract::Stimulated mast cells produce and release adenosine, and the release of mast cell mediators is potentiated by adenosine, yet very little is known regarding mast cell purine metabolism. Because 5-amino-4-imidazolecarboxamide riboside (AICA riboside) has been shown to alter adenosine metabolism and accelerate the replet...
journal_title:Biochemical pharmacology
pub_type: 杂志文章
doi:10.1016/0006-2952(86)90757-4
更新日期:1986-12-15 00:00:00
abstract::The microsomal brush-border fraction of rat renal tissue contains enzymatic activity, optimally active at pH 9, that is capable of degrading human myelin basic protein (BP) peptide 43-88. In the present study, this degradation and the effect on it of selected drugs and hormones were examined further. Of the substances...
journal_title:Biochemical pharmacology
pub_type: 杂志文章
doi:10.1016/0006-2952(85)90500-3
更新日期:1985-04-15 00:00:00
abstract::The effects of staurosporine, a protein kinase inhibitor, on the signal transduction and proliferation of thymocytes were studied. Signal transduction in response to Concanavalin A (Con A) as well as Concanavalin A (Con A)-induced augmentation of [3H]inositol incorporation into phospholipids were inhibited by staurosp...
journal_title:Biochemical pharmacology
pub_type: 杂志文章
doi:10.1016/0006-2952(92)90473-v
更新日期:1992-10-20 00:00:00
abstract::Somatostatin receptors from rabbit retinal membranes were solubilized in an active form using a mixture of the detergent n-octyl b-D-glucopyranoside (OG) and CHAPS. The binding of [125I]-Try11-somatostatin to the soluble extract was saturable and of high affinity, with an apparent affinity constant (Kd) of 0.60 +/- 0....
journal_title:Biochemical pharmacology
pub_type: 杂志文章
doi:10.1016/0006-2952(93)90439-4
更新日期:1993-05-05 00:00:00
abstract::SAD-128 was found to be an effective protector of acetylcholinesterase against inhibition by soman, due to its ability to function as a reversible inhibitor and allosteric modifier of the AChE active site. It also attenuated aging of the soman-inhibited enzyme. In order to study the connection between some of these ef...
journal_title:Biochemical pharmacology
pub_type: 杂志文章
doi:10.1016/0006-2952(90)90093-z
更新日期:1990-12-01 00:00:00