Abstract：
:We have introduced a series of point mutations into the human opioid receptor-like (ORL1) receptor and characterized them for their ability to constitutively activate G protein-coupled receptor signalling pathways. Among the 12 mutants generated, mutation at Asn133 (N133W) gave increased basal signalling through three separate pathways. N133W increased the basal activity of G14- and G16-dependent pathways by two- to three-fold. The constitutive activity of the mutant was confirmed by the finding that the enhanced activity is dependent on the level of receptor expression. In HEK-293 cells stably expressing N133W, signalling through Gi/o-dependent pathways was also observed. Radioligand binding studies revealed that the affinity for nociceptin of the wild-type ORL1 receptor and the N133W mutant do not differ significantly, suggesting that the ligand binding and signalling functions of constitutively active mutants of G protein-coupled receptors are not necessarily intrinsically linked. In conclusion, our results demonstrate that a mutation in the third transmembrane domain is able to increase the basal signalling activity of the human ORL1 receptor.
journal_name
J Neurochemjournal_title
Journal of neurochemistryauthors
Kam KW,New DC,Wong YHdoi
10.1046/j.1471-4159.2002.01231.xkeywords:
subject
Has Abstractpub_date
2002-12-01 00:00:00pages
1461-70issue
6eissn
0022-3042issn
1471-4159pii
1231journal_volume
83pub_type
杂志文章abstract：:Depletion of glutathione in the substantia nigra is one of the earliest changes observed in Parkinson's disease (PD) and could initiate dopaminergic neuronal degeneration. Nevertheless, experimental glutathione depletion does not result in preferential toxicity to dopaminergic neurons either in vivo or in vitro. Moreo...
journal_title：Journal of neurochemistry
pub_type： 杂志文章
doi：10.1046/j.1471-4159.2000.0742305.x
更新日期：2000-06-01 00:00:00
abstract：:Cultures of myelinated SJL/J fetal mouse spinal cord were incubated with serum and lymphoid cells from syngeneic animals with experimental allergic encephalomyelitis (EAE) induced by syngeneic spinal cord homogenate (SSCH) in complete Freund's adjuvant or others injected with complete Freund's adjuvant alone. After 24...
journal_title：Journal of neurochemistry
pub_type： 杂志文章
doi：10.1111/j.1471-4159.1985.tb05462.x
更新日期：1985-02-01 00:00:00
abstract：:The neuropathological and immune changes induced in the brain by 'binge drinking' have been investigated in a rat model. Evidence of neuro-inflammation was identified in the 'binge drinking' rat model of alcohol abuse after 3 weeks of administration of 2 or 3 g/kg ethanol (EtOH), three times per day for two consecutiv...
journal_title：Journal of neurochemistry
pub_type： 杂志文章
doi：10.1111/j.1471-4159.2009.06389.x
更新日期：2009-12-01 00:00:00
abstract：:Catechol-O-methyltransferase (COMT) has both soluble (S-COMT) and membrane-bound (MB-COMT) isoforms. A specific COMT antibody was used in immunohistochemical and confocal co-localization studies to explore the distribution of COMT in general in normal mice and MB-COMT in particular, in an S-COMT deficient mouse line. ...
journal_title：Journal of neurochemistry
pub_type： 杂志文章
doi：10.1111/j.1471-4159.2010.06723.x
更新日期：2010-06-01 00:00:00
abstract：:Nitric oxide (NO) has a number of physiological and pathophysiological effects in the nervous system. One target of NO is the mitochondrion, where it inhibits respiration and ATP synthesis, which may contribute to NO-mediated neuronal injury. Our recent studies suggested that impaired mitochondrial function impairs mi...
journal_title：Journal of neurochemistry
pub_type： 杂志文章
doi：10.1111/j.1471-4159.2006.03788.x
更新日期：2006-05-01 00:00:00
abstract：:The rapid bidirectional transport of dopamine beta-hydroxylase (DBH) in adrenergic axons provides a means of analyzing the life cycle of adrenergic storage vesicles. We compared the physical characteristics of DBH-containing particles traveling to or returning from the terminal varicosities of ligated rat sciatic nerv...
journal_title：Journal of neurochemistry
pub_type： 杂志文章
doi：10.1111/j.1471-4159.1989.tb07379.x
更新日期：1989-08-01 00:00:00
abstract：:The (R) and (S) forms of 5-amino-2-hydroxyvaleric acid (2-OH-DAVA) and 5-amino-4-hydroxyvaleric acid (4-OH-DAVA) were designed as structural hybrids of the 4-aminobutyric acidB (GABAB) agonist (R)-(-)-4-amino-3-hydroxybutyric acid [(R)-(-)-3-OH-GABA] and the GABAB antagonist 5-aminovaleric acid (DAVA). (S)-(-)-2-OH-DA...
journal_title：Journal of neurochemistry
pub_type： 杂志文章
doi：10.1111/j.1471-4159.1992.tb09374.x
更新日期：1992-03-01 00:00:00
abstract：:In a previous study, interleukin-1beta (IL-1beta) has been shown to induce matrix metalloproteinases (MMPs) expression through mitogen-activated protein kinases and nuclear factor-kappaB pathways in rat brain astrocytes. Moreover, transactivation of growth factor receptors and phosphatidylinositol 3-kinase (PI3K)/Akt ...
journal_title：Journal of neurochemistry
pub_type： 杂志文章
doi：10.1111/j.1471-4159.2008.05318.x
更新日期：2008-05-01 00:00:00
abstract：:We have previously purified and characterized a nervous system-specific glycoprotein antigen from adult Drosophila heads, designated Nervana [nerve antigen (NRV)] and identified two separate genes coding for three different proteins. All three proteins share homology with the beta subunits of Na+,K+-ATPase from variou...
journal_title：Journal of neurochemistry
pub_type： 杂志文章
doi：10.1046/j.1471-4159.1998.71010142.x
更新日期：1998-07-01 00:00:00
abstract：:The expression of Nex1 peaks during brain development when neurite outgrowth and synaptogenesis are highly active. We previously showed that Nex1 is a critical effector of the nerve growth factor (NGF) pathway and its overexpression results in spontaneous neuritogenesis. Furthermore, the PC12-Nex1 cells exhibit accele...
journal_title：Journal of neurochemistry
pub_type： 杂志文章
doi：10.1111/j.1471-4159.2004.02814.x
更新日期：2004-12-01 00:00:00
abstract：:The effects of fatty acids, oleate and palmitate, on gamma-aminobutyric acid (GABA), aspartate, and 3,4- dihydroxyphenylethylamine (dopamine) transport and a variety of other membrane functions were studied in rat brain synaptosomes at a constant lipid-to-protein ratio. Under the conditions utilized oleate, but not pa...
journal_title：Journal of neurochemistry
pub_type： 杂志文章
doi：10.1111/j.1471-4159.1984.tb12765.x
更新日期：1984-06-01 00:00:00
abstract：:Edaravone (Eda) is a potent scavenger of hydroxyl radicals and has been demonstrated to be beneficial for patients with acute ischemic stroke. This study was set out to investigate whether Eda protect against MPP(+)-induced cytotoxicity in rat primary cultured astrocytes. The results showed that pre-treatment with Eda...
journal_title：Journal of neurochemistry
pub_type： 杂志文章
doi：10.1111/j.1471-4159.2008.05573.x
更新日期：2008-09-01 00:00:00
abstract：:Several cholinesterase inhibitors used in the treatment of Alzheimer's disease (AD) have been shown to interact with an allosteric site on the nicotinic acetylcholine receptor (nAChR). A possible linkage between the phosphorylation state of tau, the major component of paired helical filaments found in AD brain, and st...
journal_title：Journal of neurochemistry
pub_type： 杂志文章
doi：10.1046/j.1471-4159.2000.740777.x
更新日期：2000-02-01 00:00:00
abstract：:Complex biological systems are best modeled as highly modular, fluid systems exhibiting a plasticity that allows them to adapt to a vast array of changing conditions. Here we highlight several novel network-based approaches to elucidate genetic networks underlying complex traits. These integrative genomic approaches c...
journal_title：Journal of neurochemistry
pub_type： 杂志文章
doi：10.1111/j.1471-4159.2006.03661.x
更新日期：2006-04-01 00:00:00
abstract：:Glutamate is the major excitatory transmitter in the vertebrate brain and its extracellular levels are tightly regulated to prevent excitotoxic effects. The Na(+)-dependent glutamate/aspartate transporter GLAST/EAAT1 is regulated in the short and in the long term by glutamate. A receptors-independent change in its mem...
journal_title：Journal of neurochemistry
pub_type： 杂志文章
doi：10.1111/j.1471-4159.2007.04517.x
更新日期：2007-05-01 00:00:00
abstract：:The effect of selective inhibition of monoamine oxidase (MAO) subtypes A and B on striatal metabolism of DOPA to dopamine (DA), 3,4-dihydroxyphenylacetic acid (DOPAC), and 4-hydroxy-3-methoxyphenylacetic acid (homovanillic acid; HVA) was studied in halothane-anesthetized rats 3 weeks after unilateral 6-hydroxydopamine...
journal_title：Journal of neurochemistry
pub_type： 杂志文章
doi：10.1046/j.1471-4159.1995.65031213.x
更新日期：1995-09-01 00:00:00
abstract：:Rapid axonal transport of proteins in retinal ganglion cells of the rabbit was studied following intraocular injections of labelled amino acids. Approximately 10% of the transported radioactivity was found in the supernatant following homogenization and high-speed centrifugation of the nerve terminal region. Relativel...
journal_title：Journal of neurochemistry
pub_type： 杂志文章
doi：10.1111/j.1471-4159.1976.tb00320.x
更新日期：1976-11-01 00:00:00
abstract：:Uptake and release of alanine were measured in lumbar sympathetic chains excised from embryos of white leghorn chickens, 14-15 days old, and incubated in a modified Eagle's minimum essential medium. In the presence of [U-14C]glucose, glucose carbon accumulated in alanine in the medium at a rate that increased when unl...
journal_title：Journal of neurochemistry
pub_type： 杂志文章
doi：10.1111/j.1471-4159.1984.tb12804.x
更新日期：1984-09-01 00:00:00
abstract：:Thirteen-lined ground squirrels (Ictidomys tridecemlineatus) have an extraordinary capacity to withstand prolonged and profound reductions in blood flow and oxygen delivery to the brain without incurring any cellular damage. As such, the hibernation torpor of I. tridecemlineatus provides a valuable model of tolerance ...
journal_title：Journal of neurochemistry
pub_type： 杂志文章
doi：10.1111/jnc.13368
更新日期：2015-12-01 00:00:00
abstract：:Vascular endothelial growth factor (VEGF) is a neurotrophic factor essential for maintenance of motor neurons. Loss of this factor produces a phenotype similar to amyotrophic lateral sclerosis (ALS). We recently showed that ALS-producing mutations of Cu/Zn-superoxide dismutase (SOD1) disrupt post-transcriptional regul...
journal_title：Journal of neurochemistry
pub_type： 杂志文章
doi：10.1111/j.1471-4159.2008.05856.x
更新日期：2009-02-01 00:00:00
abstract：:Precise cellular targeting of macromolecular cargos has important biotechnological and medical implications. Using a recently established 'protein stapling' method, we linked the proteolytic domain of botulinum neurotoxin type A (BoNT/A) to a selection of ligands to target neuroendocrine tumor cells. The botulinum pro...
journal_title：Journal of neurochemistry
pub_type： 杂志文章
doi：10.1111/jnc.12284
更新日期：2013-07-01 00:00:00
abstract：:Postischemic recovery from brain edema and of protein synthesis was examined following 1 h of middle cerebral artery (MCA) occlusion in rats. Recovery from brain edema and of protein synthesis showed a good correlation until 7 days after reperfusion in each area (cerebral cortex or lateral caudate) in the occluded MCA...
journal_title：Journal of neurochemistry
pub_type： 杂志文章
doi：10.1111/j.1471-4159.1988.tb01113.x
更新日期：1988-11-01 00:00:00
abstract：:2,4,5-Trihydroxyphenylalanine (6-OH-DOPA) destroys central and peripheral noradrenergic neurons, while sparing dopaminergic neurons. Previous studies indicate that 6-OH-DOPA toxicity is mediated by the formation of 6-hydroxydopamine. However, levels of 6-hydroxydopamine in brain following peripheral administration of ...
journal_title：Journal of neurochemistry
pub_type： 杂志文章
doi：10.1111/j.1471-4159.1989.tb09194.x
更新日期：1989-05-01 00:00:00
abstract：:Converging lines of evidence suggest that progressive accumulation of the amyloid beta-protein (A beta) plays a central role in the genesis of Alzheimer's disease, but it was long assumed that A beta had to be assembled into extracellular amyloid fibrils to exert its cytotoxic effects. Over the past decade, data have ...
journal_title：Journal of neurochemistry
pub_type： 杂志文章,评审
doi：10.1111/j.1471-4159.2006.04426.x
更新日期：2007-06-01 00:00:00
abstract：:Using optical imaging of retinal ganglion cell (RGC) calcium dynamics in living intact retinal wholemount preparations, we tested whether RGCs in an experimental rat glaucoma model were more sensitive to exogenously applied glutamate as a result of deficient glutamate clearance mechanisms. In contrast to post-natal ra...
journal_title：Journal of neurochemistry
pub_type： 杂志文章
doi：10.1111/j.1471-4159.2005.03214.x
更新日期：2005-08-01 00:00:00
abstract：:In adult New Zealand white rabbits, the effects of food deprivation and of massive elevations of plasma uridine or thymidine concentrations on CSF and plasma nucleoside and oxypurine concentrations were studied. Nucleoside and oxypurine levels were determined by high performance liquid chromatography using unequivocal...
journal_title：Journal of neurochemistry
pub_type： 杂志文章
doi：10.1111/j.1471-4159.1984.tb12751.x
更新日期：1984-06-01 00:00:00
abstract：:Calcitonin gene-related peptide-like immunoreactivity (CGRP-LI) was measured in selected regions of the cervical, thoracic, and lumbar spinal cord of untreated rabbits and, following intrathecal injection of the serotonergic neurotoxin 5,7-dihydroxytryptamine (5,7-DHT), in the thoracolumbar cord in rats using a sheep ...
journal_title：Journal of neurochemistry
pub_type： 杂志文章
doi：10.1111/j.1471-4159.1992.tb08434.x
更新日期：1992-10-01 00:00:00
abstract：:Addiction is thought to be a memory process between perception and environmental cues and addicted patients often relapse when they come into contact with the drug-related context once again. Here, we used a conditioned place preference protocol to seek a more effective extinction methodology of methamphetamine (METH)...
journal_title：Journal of neurochemistry
pub_type： 杂志文章
doi：10.1111/jnc.13525
更新日期：2016-04-01 00:00:00
abstract：:Rat retina tissue contains relatively high amounts of GD3 in relation to ganglio-series gangliosides even in the adult stages. This was attributed in part to an activity ratio between the enzyme that converts GM3 to GD3 [sialytransferase II (ST-II)] and the enzyme that converts GM3 to GM2 [N-acetylgalactosaminyltransf...
journal_title：Journal of neurochemistry
pub_type： 杂志文章
doi：10.1046/j.1471-4159.1995.64031274.x
更新日期：1995-03-01 00:00:00
abstract：:In the early postnatal period, energy metabolism in the suckling rodent brain relies to a large extent on metabolic pathways alternate to glucose such as the utilization of ketone bodies (KBs). However, how KBs affect neuronal excitability is not known. Using recordings of single NMDA and GABA-activated channels in ne...
journal_title：Journal of neurochemistry
pub_type： 杂志文章
doi：10.1111/j.1471-4159.2009.06230.x
更新日期：2009-08-01 00:00:00
