Abstract：
:There is much evidence to suggest that G protein coupled receptors exist as oligomers but the relevance to their function is unclear. We have, therefore, examined the binding of the radiolabelled agonist [(3)H]NPA to membranes of CHO cells expressing the D(2) dopamine receptor in dissociation rate experiments. When [(3)H]NPA dissociation was started by dilution, the dissociation rate in the absence of sodium ions was unaffected by addition of the antagonist/inverse agonist (+)-butaclamol, but was accelerated by addition of agonists e.g. dopamine, suggesting that the receptor was not behaving as a monomer with a single binding site. The very low efficacy partial agonist, aripiprazole provided an intermediate level of acceleration of dissociation. [(3)H]NPA dissociation experiments started by addition of ligands without dilution gave a similar pattern. [(3)H]NPA dissociation could also be accelerated by GTP. Dissociation of [(3)H]NPA in the presence of GTP and dopamine provided a greater acceleration than for either modulator alone, suggesting synergistic effects related to receptor/G protein interaction. When [(3)H]NPA dissociation experiments were performed in the presence of sodium ions, dissociation was faster than in their absence but the rate still depended on the ligand present in the assay. Overall the data cannot be explained by a ternary complex model and are consistent with an oligomeric receptor in which binding of [(3)H]NPA, as an example of an agonist ligand, can be modulated co-operatively by ligands binding elsewhere in the oligomer. Interactions with G proteins also occurs providing further modulation of [(3)H]NPA binding. Both agonists and G proteins are proposed to modulate the oligomer by switching high affinity agonist binding sites to low affinity sites.
journal_name
J Neurochemjournal_title
Journal of neurochemistryauthors
Kara E,Lin H,Strange PGdoi
10.1111/j.1471-4159.2009.06554.xsubject
Has Abstractpub_date
2010-03-01 00:00:00pages
1442-53issue
6eissn
0022-3042issn
1471-4159pii
JNC6554journal_volume
112pub_type
杂志文章abstract：:Obesity is a worldwide health problem that urgently needs to be solved. Leptin is an anti-obesity hormone that activates satiety signals to the brain. Evidence to suggest that leptin resistance is involved in the development of obesity is increasing; however, the molecular mechanisms involved remain unclear. We herein...
journal_title：Journal of neurochemistry
pub_type： 杂志文章
doi：10.1111/jnc.13057
更新日期：2015-05-01 00:00:00
abstract：:There is increasing evidence that a number of cytokines and their receptors are involved in the processes that lead to the development and maintenance of neuropathic pain states. Here we demonstrate that levels of CX3CR1 (the receptor for the chemokine fractalkine) mRNA in lumbar dorsal root ganglia (DRG) increase 5.8...
journal_title：Journal of neurochemistry
pub_type： 杂志文章
doi：10.1111/j.1471-4159.2008.05419.x
更新日期：2008-07-01 00:00:00
abstract：:To better understand metabotropic/ionotropic integration in neurons we have examined the regulation of M1 muscarinic acetylcholine (mACh) receptor signalling in mature (> 14 days in vitro), synaptically-active hippocampal neurons in culture. Using a protocol where neurons are exposed to an EC(50) concentration of the ...
journal_title：Journal of neurochemistry
pub_type： 杂志文章
doi：10.1111/j.1471-4159.2007.04931.x
更新日期：2007-12-01 00:00:00
abstract：:Perilymph, which bathes the sensory cells of the cochlea, was collected from guinea pigs exposed to noise and analyzed via two cation-exchange HPLC procedures with fluorescence detection, resolving 51 and 81 primary-amine compounds, respectively, at a sensitivity limit of 0.1 pmol relative to leucine. During a first p...
journal_title：Journal of neurochemistry
pub_type： 杂志文章
doi：10.1111/j.1471-4159.1983.tb04745.x
更新日期：1983-08-01 00:00:00
abstract：:PK 11195 [1-(2-chlorophenyl)-N-methyl-N-(1-methylpropyl)-3-isoquinolinecarboxamide] is a new ligand for the "peripheral-type" benzodiazepine binding sites, chemically unrelated to benzodiazepines. It displaces with a very high potency (IC50 congruent to 10(-9) M) [3H]-RO5-4864 (a benzodiazepine which specifically labe...
journal_title：Journal of neurochemistry
pub_type： 杂志文章
doi：10.1111/j.1471-4159.1983.tb00888.x
更新日期：1983-12-01 00:00:00
abstract：:Pituitary adenylate cyclase-activating polypeptide (PACAP) gene expression was analyzed in PC12 cells. PC12 cells transfected with a PACAP promoter-luciferase reporter construct were utilized to investigate the effects of PACAP, either alone or in combination with nerve growth factor (NGF), on PACAP transcriptional re...
journal_title：Journal of neurochemistry
pub_type： 杂志文章
doi：10.1046/j.1471-4159.2000.740501.x
更新日期：2000-02-01 00:00:00
abstract：:We show that the expression of the gene encoding glial fibrillary acidic protein (GFAP) gene is affected by at least three cis-acting elements. A positive regulatory element that is located between nucleotides -1,631 and -1,479 can confer cell type-specific expression on a heterologous gene. A second regulatory elemen...
journal_title：Journal of neurochemistry
pub_type： 杂志文章
doi：10.1111/j.1471-4159.1991.tb03799.x
更新日期：1991-08-01 00:00:00
abstract：:For more than three decades, the venom of the black widow spider and its principal active components, latrotoxins, have been used to induce release of neurotransmitters and hormones and to study the mechanisms of exocytosis. Given the complex nature of alpha--latrotoxin (alpha-LTX) actions, this research has been cont...
journal_title：Journal of neurochemistry
pub_type： 杂志文章,评审
doi：10.1111/j.1471-4159.2009.06329.x
更新日期：2009-10-01 00:00:00
abstract：:Five subtypes of the muscarinic receptor have been cloned from both the rat and human genomes. Although all five genes have the coding sequences in a single exon, their structures 5' of the initiation codon are largely uncharacterized, except for the M4 receptor. In the brain, muscarinic receptors mediate motor and me...
journal_title：Journal of neurochemistry
pub_type： 杂志文章
doi：10.1046/j.1471-4159.1999.0720900.x
更新日期：1999-03-01 00:00:00
abstract：:The biological activities of maitotoxin are strictly dependent on the extracellular calcium concentration and are always associated with an increase of the free cytosolic calcium level. We tested the effects of voltage-sensitive calcium channel blockers (nicardipine and omega-conotoxin) on maitotoxin-induced intracell...
journal_title：Journal of neurochemistry
pub_type： 杂志文章
doi：10.1111/j.1471-4159.1992.tb09422.x
更新日期：1992-08-01 00:00:00
abstract：:A dramatic loss of glutamate transport has been observed in sporadic amyotrophic lateral sclerosis and has been postulated to contribute to the disease. Experimentally, this hypothesis was corroborated by mimicking the chronic loss of glutamate transport in postnatal rat spinal cord organotypic cultures through the us...
journal_title：Journal of neurochemistry
pub_type： 杂志文章
doi：10.1046/j.1471-4159.1995.65020643.x
更新日期：1995-08-01 00:00:00
abstract：:Primary neuronal cultures from 8-day-old rat cerebellum were incubated in the presence of exogenously added 16 nM [gamma-32P]ATP. Phosphorylation of a 45-kDa endogenous protein was detected within 1 min and increased linearly for approximately 20 min. Unlike what was seen with [gamma-32P]ATP, in the presence of [32P]o...
journal_title：Journal of neurochemistry
pub_type： 杂志文章
doi：10.1046/j.1471-4159.1994.63062028.x
更新日期：1994-12-01 00:00:00
abstract：:In the preceding report we demonstrated a dose-dependent increase in 32P-phosphoprotein labeling after 24-h exposure of cultured cerebellar granule neurons to methyl mercury (MeHg), a response that was not observed in glial cultures. In the present study we have examined 32P-labeled phosphoproteins by two-dimensional ...
journal_title：Journal of neurochemistry
pub_type： 杂志文章
doi：10.1111/j.1471-4159.1990.tb04579.x
更新日期：1990-09-01 00:00:00
abstract：:We applied our in vivo fatty acid method to examine concentrations, incorporation, and turnover rates of docosahexaenoic acid (22:6 n-3) in brains of rats subject to a dietary deficiency of alpha-linolenic acid (18:3 n-3) for three generations. Adult deficient and adequate rats of the F3 generation were infused intrav...
journal_title：Journal of neurochemistry
pub_type： 杂志文章
doi：10.1046/j.1471-4159.2000.0752392.x
更新日期：2000-12-01 00:00:00
abstract：:A glycoprotein ATPase in cholinergic synaptic vesicles of Torpedo electric organ was solubilized with octa-ethylene glycol dodecyl ether detergent. Study of potential stabilizing factors identified crude brain phosphatidylserine, glycerol, dithiothreitol, and protease inhibitors as of value in maintaining activity. Th...
journal_title：Journal of neurochemistry
pub_type： 杂志文章
doi：10.1111/j.1471-4159.1989.tb08524.x
更新日期：1989-11-01 00:00:00
abstract：:After intraperitoneal injection of rats with 6-fluorotryptophan (6-FT), brain 5-hydroxytryptamine (5-HT) levels decreased exponentially over 1 h. Depletion was dose-dependent and maximum depletion was observed at 200 mg/kg. 6-FT (200 mg/kg) did not significantly alter the content of 5-hydroxyindoleacetic acid. Turnove...
journal_title：Journal of neurochemistry
pub_type： 杂志文章
doi：10.1111/j.1471-4159.1987.tb05704.x
更新日期：1987-05-01 00:00:00
abstract：:The MRC OX-2 monoclonal antibody recognises membrane glycoproteins of Mr 41,000 in rat brain and 47,000 on thymocytes. It also reacts with follicular dendritic cells in lymphoid organs, endothelium, smooth muscle, and B-lymphocytes. Indirect immunoperoxidase staining of cryostat sections showed that OX-2 antigen was p...
journal_title：Journal of neurochemistry
pub_type： 杂志文章
doi：10.1111/j.1471-4159.1984.tb12844.x
更新日期：1984-10-01 00:00:00
abstract：:To study potential biochemical correlates of dopamine (DA) and serotonin receptor supersensitivity, rats were lesioned at 3 days after birth with 6-hydroxydopamine (6-OHDA; 67 micrograms in each lateral ventricle; desipramine pretreatment, 20 mg/kg i.p., 1 h) and then sensitized with the DA D1 agonist, SKF 38393 HCl (...
journal_title：Journal of neurochemistry
pub_type： 杂志文章
doi：10.1046/j.1471-4159.1994.63041282.x
更新日期：1994-10-01 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：:The effect of a unilateral perinatal hypoxic-ischemic brain injury on dopamine D1 and D2 receptors and uptake sites was investigated in rats by using in vitro quantitative binding autoradiography, 2-3 weeks after the insult. We observed significant decreases in the Bmax and KD for [3H]SCH 23390-labeled D1 and in the B...
journal_title：Journal of neurochemistry
pub_type： 杂志文章
doi：10.1111/j.1471-4159.1991.tb06409.x
更新日期：1991-12-01 00:00:00
abstract：:Alzheimer's disease (AD) is characterized by amyloid-beta peptide (Abeta) deposition in the brain. Abeta is produced by sequential cleavage of amyloid precursor protein (APP) by beta-secretase (BACE1: beta-site APP-cleaving enzyme 1) and gamma-secretase. Previously, we demonstrated that BACE1 also cleaves beta-galacto...
journal_title：Journal of neurochemistry
pub_type： 杂志文章
doi：10.1111/j.1471-4159.2005.03595.x
更新日期：2006-02-01 00:00:00
abstract：:In a previous study we showed that in vivo treatment with pertussis toxin could inhibit some, but not all, effects of adenosine in the rat hippocampus. In this study we investigated the effect of pertussis toxin on the binding of adenosine analogues to A1 receptors in rat brain. Intraventricular injection of pertussis...
journal_title：Journal of neurochemistry
pub_type： 杂志文章
doi：10.1111/j.1471-4159.1992.tb11332.x
更新日期：1992-04-01 00:00:00
abstract：:We have shown previously that the plecomacrolide antibiotics bafilomycin A1 and B1 significantly attenuate cerebellar granule neuron death resulting from agents that disrupt lysosome function. To further characterize bafilomycin-mediated cytoprotection, we examined its ability to attenuate the death of naïve and diffe...
journal_title：Journal of neurochemistry
pub_type： 杂志文章
doi：10.1111/j.1471-4159.2010.06838.x
更新日期：2010-08-01 00:00:00
abstract：:High-affinity binding sites (apparent KD = 1.5 nM) for [3H]desipramine have been demonstrated and characterized in membranes prepared from rat brain. The binding of [3H]desipramine was found to be saturable, reversible, heat-sensitive, sodium-dependent, and regionally distributed among various regions of the brain. Hi...
journal_title：Journal of neurochemistry
pub_type： 杂志文章
doi：10.1111/j.1471-4159.1982.tb05326.x
更新日期：1982-04-01 00:00:00
abstract：:Primary cortical neurones exposed to an oxidative insult in the form of hydrogen peroxide (H(2)O(2)) for 30 min showed a concentration-dependent increase in oxidative stress followed by a delayed NMDA receptor-dependent cell death measured 24 h later. Extracellular signal-regulated protein kinase (ERK1/2), c-jun N-ter...
journal_title：Journal of neurochemistry
pub_type： 杂志文章
doi：10.1046/j.0022-3042.2001.00637.x
更新日期：2002-01-01 00:00:00
abstract：:Major depressive disorder is a severe and chronic illness with high lifetime prevalence and a high incidence of suicide as the cause of death for patients with this diagnosis. Major depressive disorder is often treated with anti-depressants. Although these drugs have been used for many years, their exact mode of actio...
journal_title：Journal of neurochemistry
pub_type： 杂志文章,评审
doi：10.1111/jnc.13145
更新日期：2015-07-01 00:00:00
abstract：:Several lines of evidence indicate that a rapid loss of neuronal protein kinase C (PKC) activity is a characteristic feature of cerebral ischemia and is a necessary step in the NMDA-induced death of cultured neurons. Exposing embryonic day 18 primary rat cortical neurons to 50 microM NMDA or 50 microM glutamate for 10...
journal_title：Journal of neurochemistry
pub_type： 杂志文章
doi：10.1046/j.1471-4159.1999.0720102.x
更新日期：1999-01-01 00:00:00
abstract：:Blood-based tests for the differential diagnosis of Alzheimer's disease (AD) are under intensive investigation and have shown promising results with regard to Abeta40 and Abeta42 peptide species in incipient AD. Moreover, plasma Abeta40 was suggested as an independent cerebrovascular risk factor candidate. These consi...
journal_title：Journal of neurochemistry
pub_type： 杂志文章
doi：10.1111/j.1471-4159.2007.04763.x
更新日期：2007-10-01 00:00:00
abstract：:Beta-amyloid peptides (A beta) are deposited in an aggregated fibrillar form in both diffuse and senile plaques in the brains of patients with Alzheimer's disease. The neurotoxicity of A beta in cultured neurons is dependent on its aggregation state, but the factors contributing to aggregation and fibril formation are...
journal_title：Journal of neurochemistry
pub_type： 杂志文章
doi：10.1046/j.1471-4159.1998.70031182.x
更新日期：1998-03-01 00:00:00
abstract：:In the presence of lithium, carbamylcholine chloride (carbachol) and epinephrine increase the accumulation of inositol monophosphate severalfold in hippocampal slices from the rat. The stimulation by carbachol (EC50, 31 microM) is mediated by muscarinic receptors, whereas the effects of epinephrine (EC50, 2 microM) ar...
journal_title：Journal of neurochemistry
pub_type： 杂志文章
doi：10.1111/j.1471-4159.1988.tb02947.x
更新日期：1988-02-01 00:00:00
