Abstract：
:GABA(A) receptors are the major inhibitory neurotransmitter receptors in the brain. Some of them are targets of benzodiazepines that are widely used in clinical practice for their sedative/hypnotic, anxiolytic, muscle relaxant and anticonvulsant effects. In order to rationally separate these different drug actions, we need to understand the interaction of such compounds with the benzodiazepine-binding pocket. With this aim, we mutated residues located in the benzodiazepine-binding site individually to cysteine. These mutated receptors were combined with benzodiazepine site ligands carrying a cysteine reactive group in a defined position. Proximal apposition of reaction partners will lead to a covalent reaction. We describe here such proximity-accelerated chemical coupling reactions of alpha(1)S205C and alpha(1)T206C with a diazepam derivative modified at the C-3 position with a reactive isothiocyanate group (-NCS). We also provide new data that identify alpha(1)H101C and alpha(1)N102C as exclusive sites of the reaction of a diazepam derivative where the -Cl atom is replaced by a -NCS group. Based on these observations we propose a relative positioning of diazepam within the benzodiazepine-binding site of alpha(1)beta(2)gamma(2) receptors.
journal_name
J Neurochemjournal_title
Journal of neurochemistryauthors
Tan KR,Baur R,Charon S,Goeldner M,Sigel Edoi
10.1111/j.1471-4159.2009.06419.xsubject
Has Abstractpub_date
2009-12-01 00:00:00pages
1264-73issue
5eissn
0022-3042issn
1471-4159pii
JNC6419journal_volume
111pub_type
杂志文章abstract：:Challenge of protease-activated receptors induces cytosolic Ca(2+) concentration ([Ca(2+) ](c)) increase, mitogen-activated protein kinase activation and reactive oxygen species (ROS) formation with a bandwidth of responses in individual cells. We detected in this study in situ the thrombin-induced [Ca(2+) ](c) rise a...
journal_title：Journal of neurochemistry
pub_type： 杂志文章
doi：10.1111/j.1471-4159.2011.07527.x
更新日期：2011-12-01 00:00:00
abstract：:Current evidence indicates that glutamate acting via the N-methyl-D-aspartate (NMDA) receptor/ion channel complex plays a major role in the neuronal degeneration associated with a variety of neurological disorders. In this report the role of glycine in NMDA neurotoxicity was examined. We demonstrate that NMDA-mediated...
journal_title：Journal of neurochemistry
pub_type： 杂志文章
doi：10.1111/j.1471-4159.1990.tb02329.x
更新日期：1990-03-01 00:00:00
abstract：:Drosophila melanogaster homogenates incubated with tritiated 5-hydroxytryptophan, 5-hydroxytryptamine, or N-acetylserotonin have the ability of converting them into labelled indolamines, including melatonin. All these compounds were characterized by two-dimensional thin-layer chromatography by comparison with nonradio...
journal_title：Journal of neurochemistry
pub_type： 杂志文章
doi：10.1111/j.1471-4159.1988.tb02923.x
更新日期：1988-02-01 00:00:00
abstract：:The NMDA receptor has recently been found to be phosphorylated on tyrosine. To assess the possible connection between tyrosine phosphorylation of the NMDA receptor and signaling pathways in the postsynaptic cell, we have investigated the relationship between tyrosine phosphorylation and the binding of NMDA receptor su...
journal_title：Journal of neurochemistry
pub_type： 杂志文章
doi：10.1046/j.1471-4159.1997.69020623.x
更新日期：1997-08-01 00:00:00
abstract：:Alpha-amino-3-hydroxy-5-methylisoxazole-4-propionic acid glutamate receptors have been shown to modulate the morphology of the lamelar processes of Bergmann glia cells in the molecular layer of the cerebellum. Here we suggest that reorganization of F-actin may underlay the changes in the morphology of the lamelar proc...
journal_title：Journal of neurochemistry
pub_type： 杂志文章
doi：10.1111/jnc.14658
更新日期：2019-04-01 00:00:00
abstract：:The effects of a novel nonpeptide NK1 tachykinin receptor antagonist, SR 140333, on the functional consequences of NK1 receptor activation in a human astrocytoma cell line, U373MG, were investigated. Radioligand binding conducted with 125I-Bolton-Hunter substance P revealed a competitive inhibition by SR 140333 and it...
journal_title：Journal of neurochemistry
pub_type： 杂志文章
doi：10.1046/j.1471-4159.1994.62041399.x
更新日期：1994-04-01 00:00:00
abstract：:In Aplysia, serotonin mediates behavioral sensitization by increasing the strength of the synapse between sensory and motor neurons, a process known as facilitation. The retention of long-term facilitation is blocked by rapamycin, an inhibitor of a specific translational pathway. One possible rapamycin-sensitive targe...
journal_title：Journal of neurochemistry
pub_type： 杂志文章
doi：10.1111/j.1471-4159.2004.02634.x
更新日期：2004-09-01 00:00:00
abstract：:During development, dynamic changes in the axonal growth cone and dendrite are necessary for exploratory movements underlying initial axo-dendritic contact and ultimately the formation of a functional synapse. In the adult central nervous system, an impressive degree of plasticity is retained through morphological and...
journal_title：Journal of neurochemistry
pub_type： 杂志文章,评审
doi：10.1111/jnc.12502
更新日期：2014-04-01 00:00:00
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journal_title：Journal of neurochemistry
pub_type： 杂志文章
doi：10.1111/j.1471-4159.1982.tb12525.x
更新日期：1981-09-01 00:00:00
abstract：:Ketamine is an anesthetic that exhibits analgesic, psychotomimetic, and rapid antidepressant effects that are of particular neuropharmacological interest. Recent studies revealed astrocytic Ca(2+) signaling and regulated exocytosis as ketamine-targeted processes. Thus high-resolution cell-attached membrane capacitance...
journal_title：Journal of neurochemistry
pub_type： 杂志文章
doi：10.1111/jnc.13715
更新日期：2016-09-01 00:00:00
abstract：:Liver fatty acid-binding protein (FABP1, L-FABP) has high affinity for and enhances uptake of arachidonic acid (ARA, C20:4, n-6) which, when esterified to phospholipids, is the requisite precursor for synthesis of endocannabinoids (EC) such as arachidonoylethanolamide (AEA) and 2-arachidonoylglycerol (2-AG). The brain...
journal_title：Journal of neurochemistry
pub_type： 杂志文章
doi：10.1111/jnc.13664
更新日期：2016-08-01 00:00:00
abstract：:This study investigated the temporal expression and cell subtype distribution of activated caspase-3 following cortical impact-induced traumatic brain injury in rats. The animals were killed and examined for protein expression of the proteolytically active subunit of caspase-3, p18, at intervals from 6 h to 14 days af...
journal_title：Journal of neurochemistry
pub_type： 杂志文章
doi：10.1046/j.1471-4159.2000.0751264.x
更新日期：2000-09-01 00:00:00
abstract：:The glycine receptor is a member of the Cys-loop, ligand-gated ion channel family and is responsible for inhibition in the CNS. We examined the orientation of amino acids I229 in transmembrane 1 (TM1) and A288 in TM3, which are both critical for alcohol and volatile anesthetic action. We mutated these two amino acids ...
journal_title：Journal of neurochemistry
pub_type： 杂志文章
doi：10.1111/j.1471-4159.2007.05090.x
更新日期：2008-03-01 00:00:00
abstract：:Recent evidence indicates that tyrosine phosphorylation may play important roles in retinal photoreceptor rod outer segments (ROS). We investigated the tyrosine phosphorylation of endogenous proteins in isolated bovine ROS. Several proteins with apparent molecular masses of 31, 39, 60, 83, 90, 97, 120, 140, and 180 kD...
journal_title：Journal of neurochemistry
pub_type： 杂志文章
doi：10.1046/j.1471-4159.2000.0752006.x
更新日期：2000-11-01 00:00:00
abstract：:Intracerebral administration of [3H]arachidonic acid ([3H]ArA) into 19-20-day-old rat embryos, resulted in a rapid incorporation of label into brain lipids. One hour after injection, 55.6 +/- 8.2, 18.0 +/- 3.4, and 13.7 +/- 1.3% of the total radioactivity was associated with phosphatidylcholine, phosphatidylinositol, ...
journal_title：Journal of neurochemistry
pub_type： 杂志文章
doi：10.1111/j.1471-4159.1992.tb11014.x
更新日期：1992-11-01 00:00:00
abstract：:The RGS proteins are a recently discovered family of G protein regulators that have been shown to act as GTPase-activating proteins (GAPs) on the G(alpha i) and G(alpha q) subfamilies of the heterotrimeric G proteins. Here, we demonstrate that RGS7 is a potent GAP in vitro on G(alpha i1), and G(alpha o) heterotrimeric...
journal_title：Journal of neurochemistry
pub_type： 杂志文章
doi：10.1046/j.1471-4159.1998.70051964.x
更新日期：1998-05-01 00:00:00
abstract：:Prolonged seizures activate members of the Bcl-2 homology domain 3-only sub-group of the Bcl-2 protein family, which are essential for initiation of apoptosis signaling. Bid is a potent pro-apoptotic Bcl-2 homology domain 3-only protein, which upon proteolytic activation translocates to mitochondria to promote activat...
journal_title：Journal of neurochemistry
pub_type： 杂志文章
doi：10.1111/j.1471-4159.2010.06909.x
更新日期：2010-10-01 00:00:00
abstract：:Angiotensin II (Ang II) interacts with the neuronal AT1 receptor subtype and initiates a cascade of signaling events involving activation of Ras-Raf-1-MAP kinase. Raf-1-dependent activation of mitogen-activated protein kinase (MAPK) is the key in the chronic norepinephrine neuromodulatory actions of Ang II and is asso...
journal_title：Journal of neurochemistry
pub_type： 杂志文章
doi：10.1046/j.1471-4159.1998.70010424.x
更新日期：1998-01-01 00:00:00
abstract：:We applied a differential display PCR technique to isolate molecules that are area-specific in expression in the primate neocortex, and found that growth/differentiation factor 7 (GDF7), a member of the bone morphogenetic protein (BMP)/transforming growth factor (TGF) beta super-family, is preferentially expressed in ...
journal_title：Journal of neurochemistry
pub_type： 杂志文章
doi：10.1046/j.1471-4159.2001.00177.x
更新日期：2001-03-01 00:00:00
abstract：:Parkinson's disease is a common neurodegenerative disorder with a mainly sporadic aetiology, although a number of monogenic familiar forms are known. Most of the motor symptoms are due to selective depletion of dopaminergic, neuromelanin-containing neurones of the substantia nigra pars compacta. Neuromelanin is the da...
journal_title：Journal of neurochemistry
pub_type： 杂志文章,评审
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更新日期：2006-02-01 00:00:00
abstract：:Microtubule-associated proteins (MAPs) were phosphorylated by a Ca2+- and calmodulin-dependent protein kinase from rat brain cytosol. The maximal amount of phosphate incorporated into MAPs was 25 nmol of phosphate/mg protein. A Ka value of the enzyme for calmodulin was 57.0 nM, with MAPs as substrates. Among MAPs, MAP...
journal_title：Journal of neurochemistry
pub_type： 杂志文章
doi：10.1111/j.1471-4159.1983.tb09060.x
更新日期：1983-10-01 00:00:00
abstract：:The neuronal nitric oxide (NO) synthase generates NO from arginine. NO mediates its physiological effects mainly by stimulating the synthesis of cyclic GMP. We have investigated the role of the arginine availability on the NMDA-induced cyclic GMP accumulation in immature rat brain slices. The effect of NMDA was blocke...
journal_title：Journal of neurochemistry
pub_type： 杂志文章
doi：10.1046/j.1471-4159.1998.71052139.x
更新日期：1998-11-01 00:00:00
abstract：:The purpose of this study was to assess and compare the toxicity of beta-amyloid (Abeta) on primary cortical and mesencephalic neurons cultured with and without microglia in order to determine the mechanism underlying microglia-mediated Abeta-induced neurotoxicity. Incubation of cortical or mesencephalic neuron-enrich...
journal_title：Journal of neurochemistry
pub_type： 杂志文章
doi：10.1046/j.1471-4159.2002.01210.x
更新日期：2002-11-01 00:00:00
abstract：:Rosiglitazone is a member of the thiazolidinedione family of synthetic peroxisome proliferator-activated receptor (PPAR) agonists. It is a selective ligand of the PPARgamma subtype and functions by regulating the transcription of insulin-responsive genes. A screen of FDA-approved compounds identified rosiglitazone as ...
journal_title：Journal of neurochemistry
pub_type： 杂志文章
doi：10.1111/j.1471-4159.2009.05995.x
更新日期：2009-04-01 00:00:00
abstract：:The distribution of type I calmodulin-sensitive adenylyl cyclase in bovine and rat tissues was examined by northern blot analysis and in situ hybridization. Northern blot analysis using poly(A)(+)-selected RNA from various bovine tissues indicated that mRNA for type I adenylyl cyclase was found only in brain, retina, ...
journal_title：Journal of neurochemistry
pub_type： 杂志文章
doi：10.1111/j.1471-4159.1993.tb05852.x
更新日期：1993-01-01 00:00:00
abstract：:Rat and mouse CNS neurofilament proteins (NFPs) were characterized and compared, in terms of electrophoretic properties on polyacrylamide gels and by peptide mapping, with one another and with other co-purifying lower-molecular-weight CNS proteins, including alpha and beta tubulin. NFPs were partially purified by modi...
journal_title：Journal of neurochemistry
pub_type： 杂志文章
doi：10.1111/j.1471-4159.1981.tb02389.x
更新日期：1981-01-01 00:00:00
abstract：:Animals treated with high doses of amphetamines have been used as a model of schizophrenia due to the similarities between the psychosis associated with this mental disorder and that induced by chronic amphetamine abuse. When administered to naive rats in high doses, the amphetamine-like CNS stimulant methamphetamine ...
journal_title：Journal of neurochemistry
pub_type： 杂志文章
doi：10.1111/j.1471-4159.1985.tb12893.x
更新日期：1985-03-01 00:00:00
abstract：:Haptoglobin (Hp) binds hemoglobin (Hb) with high affinity and provides the primary defense against its toxicity after intravascular hemolysis. Neurons are exposed to extracellular Hb after CNS hemorrhage, and a therapeutic effect of Hp via Hb sequestration has been hypothesized. In this study, we tested the hypothesis...
journal_title：Journal of neurochemistry
pub_type： 杂志文章
doi：10.1111/jnc.13720
更新日期：2016-11-01 00:00:00
abstract：:IMP-GMP 5'-nucleotidase has been purified to homogeneity from total rat brain extracts. This preparation showed a unique band (Mr 54,000 +/- 1,509) in sodium dodecyl sulfate-polyacrylamide gel electrophoresis. The enzyme presented the following properties: optimal pH value, 6.5-6.8; relative velocity measured in the p...
journal_title：Journal of neurochemistry
pub_type： 杂志文章
doi：10.1046/j.1471-4159.1998.71031241.x
更新日期：1998-09-01 00:00:00
abstract：:L-3,4-Dihydroxyphenylalanine (L-dopa) is toxic for human neuroblastoma cells NB69 and its toxicity is related to several mechanisms including quinone formation and enhanced production of free radicals related to the metabolism of dopamine via monoamine oxidase type B. We studied the effect of L-DOPA on activities of e...
journal_title：Journal of neurochemistry
pub_type： 杂志文章
doi：10.1046/j.1471-4159.1995.64020576.x
更新日期：1995-02-01 00:00:00
