Abstract：
:Calcium modulates the 5-HT3 receptor response by reducing peak current amplitude and increasing rates of activation, deactivation and desensitisation, but the binding site(s) and mechanism(s) of this modulation are unknown. Here we study residues that may be involved in calcium binding in two partially overlapping regions of the extracellular domain (E213-E215-E218 and D204-E218-V219). The modulatory effects of calcium were assessed by radioligand binding and whole-cell patch-clamp. Comparisons of [3H]granisetron binding showed an increase in Kd in 10mM calcium that was abolished by the substitutions E213Q, E215Q, D204N and V219L. E218Q mutant receptors displayed no specific binding or function, and immunofluorescence showed that they did not reach the cell surface. E213Q increased inherent rates of desensitisation, but the relative effects of calcium on these rates, and on the reduction in current amplitude, were similar to wild type receptors. Current responses and calcium-mediated effects at E215Q mutant receptors were indistinguishable from wild type. D204N and V219L mutants were non-functional. A calcium impermeable mutant (E277A/S297R) revealed no changes in peak amplitude or kinetics with increased calcium. Our results are consistent with residues D204, E218 and V219 participating in receptor assembly, structure and/or trafficking to the plasma membrane, and we speculate that this might rely upon the stabilising effect of bound calcium. E213, E215, D204 and V219 may contribute to a calcium binding site that is responsible for the calcium-mediated effects on ligand binding. However, the major site for calcium-dependent modulation of the 5-HT3 current is located within the ion channel or cell interior.
journal_name
Neuropharmacologyjournal_title
Neuropharmacologyauthors
Thompson AJ,Lummis SCdoi
10.1016/j.neuropharm.2008.07.009subject
Has Abstractpub_date
2009-01-01 00:00:00pages
285-91issue
1eissn
0028-3908issn
1873-7064pii
S0028-3908(08)00285-2journal_volume
56pub_type
杂志文章abstract：:D-Tubocurarine is a potent competitive antagonist of two members of the ligand-gated ion channel family, the muscle-type nicotinic acetylcholine receptor (AChR) and serotonin type-3 receptor (5HT3R). We have used a series of analogs of D-tubocurarine to determine the effects of methylation, stereoisomerization and hal...
journal_title：Neuropharmacology
pub_type： 杂志文章
doi：10.1016/s0028-3908(98)00010-0
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pub_type： 杂志文章
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journal_title：Neuropharmacology
pub_type： 杂志文章
doi：10.1016/0028-3908(82)90024-7
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abstract：:1-Methyl-4-(2'-aminophenyl)-1,2,3,6-tetrahydropyridine (2'-NH2-MPTP) causes long-term depletions in cortical and hippocampal serotonin (5-HT) and norepinephrine (NE) that are accompanied by acute elevations in glial fibrillary acidic protein (GFAP) and argyrophilia. To further investigate the hypothesis that these cha...
journal_title：Neuropharmacology
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更新日期：1997-02-01 00:00:00
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journal_title：Neuropharmacology
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doi：10.1016/j.neuropharm.2013.03.027
更新日期：2013-08-01 00:00:00
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journal_title：Neuropharmacology
pub_type： 杂志文章
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更新日期：1994-08-01 00:00:00
abstract：:Due to the claim that lithium (Li+) reduces morphine self-administration in dependent rats, the effects of acute and chronic Li+ treatments on naloxone-precipitated withdrawal syndrome and physical dependence development to morphine in mice chronically treated with morphine, were evaluated. Morphine dependency was ind...
journal_title：Neuropharmacology
pub_type： 杂志文章
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更新日期：1995-01-01 00:00:00
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journal_title：Neuropharmacology
pub_type： 杂志文章
doi：10.1016/j.neuropharm.2018.02.003
更新日期：2018-05-01 00:00:00
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journal_title：Neuropharmacology
pub_type： 杂志文章
doi：10.1016/j.neuropharm.2008.06.016
更新日期：2008-10-01 00:00:00
abstract：:The hippocampal slice is a popular model system in which to study the cellular properties of long-term potentiation (LTP). Synaptogenesis induced by exposure to ice-cold artificial cerebrospinal fluid (ACSF), however, raises the concern that morphological correlates of LTP might be obscured, especially in mature slice...
journal_title：Neuropharmacology
pub_type： 杂志文章
doi：10.1016/j.neuropharm.2006.06.020
更新日期：2007-01-01 00:00:00
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journal_title：Neuropharmacology
pub_type： 杂志文章
doi：10.1016/j.neuropharm.2016.03.037
更新日期：2016-08-01 00:00:00
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journal_title：Neuropharmacology
pub_type： 杂志文章
doi：10.1016/j.neuropharm.2014.11.020
更新日期：2015-04-01 00:00:00
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journal_title：Neuropharmacology
pub_type： 杂志文章
doi：10.1016/0028-3908(86)90260-1
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journal_title：Neuropharmacology
pub_type： 杂志文章
doi：10.1016/0028-3908(95)00009-u
更新日期：1995-04-01 00:00:00
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journal_title：Neuropharmacology
pub_type： 杂志文章
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journal_title：Neuropharmacology
pub_type： 杂志文章
doi：10.1016/0028-3908(87)90018-9
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journal_title：Neuropharmacology
pub_type： 杂志文章
doi：10.1016/s0028-3908(97)00153-6
更新日期：1998-01-01 00:00:00
abstract：:Recent evidence suggests an early involvement of dopaminergic (DA) processes and terminals in Parkinson's disease (PD). The arborization of neurons depends on the actin cytoskeleton, which in turn is regulated by small GTPases of the Rho family, encompassing Rho, Rac and Cdc42 subfamilies. Indeed, some reports point t...
journal_title：Neuropharmacology
pub_type： 杂志文章
doi：10.1016/j.neuropharm.2016.06.016
更新日期：2016-10-01 00:00:00
abstract：:The influence of repeated administration of imipramine on the EEG and behavioural effects of clonidine has been studied in the rat bearing chronic electrodes. Clonidine induced behavioural depression and EEG synchronization in control rats. Mydriasis, hyperirritability, stereotyped behaviour and EEG desynchronization ...
journal_title：Neuropharmacology
pub_type： 杂志文章
doi：10.1016/0028-3908(82)90053-3
更新日期：1982-06-01 00:00:00
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journal_title：Neuropharmacology
pub_type： 杂志文章
doi：10.1016/0028-3908(83)90099-0
更新日期：1983-06-01 00:00:00
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journal_title：Neuropharmacology
pub_type： 杂志文章
doi：10.1016/s0028-3908(02)00376-3
更新日期：2003-02-01 00:00:00
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journal_title：Neuropharmacology
pub_type： 杂志文章
doi：10.1016/j.neuropharm.2014.05.046
更新日期：2014-10-01 00:00:00
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journal_title：Neuropharmacology
pub_type： 杂志文章
doi：10.1016/0028-3908(94)90112-0
更新日期：1994-06-01 00:00:00
abstract：:Chronic activity perturbations in neurons induce homeostatic plasticity through modulation of synaptic strength or other intrinsic properties to maintain the correct physiological range of excitability. Although similar plasticity can also occur at the population level, what molecular mechanisms are involved remain un...
journal_title：Neuropharmacology
pub_type： 杂志文章
doi：10.1016/j.neuropharm.2018.06.011
更新日期：2018-08-01 00:00:00
abstract：:G protein-coupled receptor 35 (GPR35) is an orphan G protein-coupled receptor (GPCR) that can be activated by kynurenic acid at high micromolar concentrations. A previously unappreciated mechanism of action of GPR35 has emerged as a Gαi/o-coupled inhibitor of synaptic transmission, a finding that has significant impli...
journal_title：Neuropharmacology
pub_type： 杂志文章,评审
doi：10.1016/j.neuropharm.2015.07.035
更新日期：2017-02-01 00:00:00
abstract：:Metabotropic glutamate receptor subtype 5 (mGluR5), encoded by the GRM5 gene, represents a compelling novel drug target for the treatment of schizophrenia. mGluR5 is a postsynaptic G-protein coupled glutamate receptor strongly linked with several critical cellular processes that are reported to be disrupted in schizop...
journal_title：Neuropharmacology
pub_type： 杂志文章,评审
doi：10.1016/j.neuropharm.2015.08.003
更新日期：2017-03-15 00:00:00
abstract：:Dietary supplements containing polyunsaturated fatty acids (PUFA) are frequently taken for their perceived health benefits including a possible reduction in cognitive decline in the elderly. Here we report that pre-treatment with docosahexaenoic acid (DHA) or eicosapentaenoic acid (EPA) significantly reduced the survi...
journal_title：Neuropharmacology
pub_type： 杂志文章
doi：10.1016/j.neuropharm.2008.02.003
更新日期：2008-05-01 00:00:00
