Abstract：
:The Erwinia ligand-gated ion channel (ELIC) is a bacterial homologue of vertebrate Cys-loop ligand-gated ion channels. It is activated by GABA, and this property, combined with its structural similarity to GABA(A) and other Cys-loop receptors, makes it potentially an excellent model to probe their structure and function. Here we characterise the pharmacological profile of ELIC, examining the effects of compounds that could activate or inhibit the receptor. We confirm that a range of amino acids and classic GABA(A) receptor agonists do not elicit responses in ELIC, and we show the receptor can be at least partially activated by 5-aminovaleric acid and γ-hydroxybutyric acid, which are weak agonists. A range of GABA(A) receptor non-competitive antagonists inhibit GABA-elicited ELIC responses including α-endosulfan (IC₅₀ = 17 μM), dieldrin (IC₅₀ = 66 μM), and picrotoxinin (IC₅₀ = 96 μM) which were the most potent. Docking suggested possible interactions at the 2' and 6' pore-lining residues, and mutagenesis of these residues supports this hypothesis for α-endosulfan. A selection of compounds that act at Cys-loop and other receptors also showed some efficacy at blocking ELIC responses, but most were of low potency (IC₅₀ > 100 μM). Overall our data show that a number of compounds can inhibit ELIC, but it has limited pharmacological similarity to GLIC and to Cys-loop receptors.
journal_name
Neuropharmacologyjournal_title
Neuropharmacologyauthors
Thompson AJ,Alqazzaz M,Ulens C,Lummis SCdoi
10.1016/j.neuropharm.2012.05.027subject
Has Abstractpub_date
2012-09-01 00:00:00pages
761-7issue
4eissn
0028-3908issn
1873-7064pii
S0028-3908(12)00225-0journal_volume
63pub_type
杂志文章abstract：:The neuroactive steroid (NAS) tetrahydrodeoxycorticosterone (THDOC) increases protein kinase C (PKC) mediated phosphorylation of extrasynaptic GABAA receptor (GABAAR) subunits leading to increased surface expression of α4/β3 subunit-containing extrasynaptic GABAARs, leading to a sustained increase in GABAAR tonic curr...
journal_title：Neuropharmacology
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doi：10.1016/j.neuropharm.2016.10.010
更新日期：2017-02-01 00:00:00
abstract：:We have used patch-clamp recording from cultured neurones, immunohistochemistry and gene deletion techniques to characterize the P2X receptors present in mouse otic ganglion neurones, and demonstrated the presence of similar receptors in rat neurones. All neurones from wild-type (WT) mice responded to ATP (EC(50) 109 ...
journal_title：Neuropharmacology
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doi：10.1016/j.neuropharm.2004.01.009
更新日期：2004-06-01 00:00:00
abstract：:Family, twin and adoption studies demonstrate clearly that alcohol dependence and alcohol use disorders are phenotypically complex and heritable. The heritability of alcohol use disorders is estimated at approximately 50-60% of the total phenotypic variability. Vulnerability to alcohol use disorders can be due to mult...
journal_title：Neuropharmacology
pub_type： 杂志文章,评审
doi：10.1016/j.neuropharm.2017.01.017
更新日期：2017-08-01 00:00:00
abstract：:The reported effects of nitric oxide (NO) on dopamine release from the striatum are variable and its precise effect on striatal nerve terminals is unclear. In the present study a novel method of applying NO to brain tissue in situ was employed. Photo-activation of Roussin's Black Salt (RBS), retained in isolated perfu...
journal_title：Neuropharmacology
pub_type： 杂志文章
doi：10.1016/0028-3908(94)90037-x
更新日期：1994-11-01 00:00:00
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journal_title：Neuropharmacology
pub_type： 杂志文章
doi：10.1016/0028-3908(94)90072-8
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journal_title：Neuropharmacology
pub_type： 杂志文章
doi：10.1016/s0028-3908(99)00221-x
更新日期：2000-04-27 00:00:00
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journal_title：Neuropharmacology
pub_type： 杂志文章
doi：10.1016/j.neuropharm.2005.12.008
更新日期：2006-06-01 00:00:00
abstract：:In PC12 cells, isosorbide dinitrate (ISDN) and S-nitrosol-acetyl-penicillamine (SNAP), both nitric oxide (NO) generators, attenuated K+ (56 mM)-stimulated release of dopamine. The attenuation was not observed with isosorbide, an ISDN analog lacking NO generating capacity. In this model, A23187 (Ca2+ ionophore), Bay K8...
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pub_type： 杂志文章
doi：10.1016/0028-3908(94)00151-h
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journal_title：Neuropharmacology
pub_type： 杂志文章,评审
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更新日期：2015-09-01 00:00:00
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journal_title：Neuropharmacology
pub_type： 杂志文章
doi：10.1016/j.neuropharm.2004.03.010
更新日期：2004-07-01 00:00:00
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pub_type： 杂志文章
doi：10.1016/s0028-3908(98)00042-2
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journal_title：Neuropharmacology
pub_type： 杂志文章,评审
doi：10.1016/j.neuropharm.2006.07.027
更新日期：2007-01-01 00:00:00
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journal_title：Neuropharmacology
pub_type： 杂志文章,评审
doi：10.1016/0028-3908(83)90114-4
更新日期：1983-12-01 00:00:00
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journal_title：Neuropharmacology
pub_type： 杂志文章
doi：10.1016/0028-3908(87)90090-6
更新日期：1987-09-01 00:00:00
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journal_title：Neuropharmacology
pub_type： 杂志文章
doi：10.1016/j.neuropharm.2017.09.019
更新日期：2018-01-01 00:00:00
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journal_title：Neuropharmacology
pub_type： 杂志文章
doi：10.1016/j.neuropharm.2016.12.018
更新日期：2017-04-01 00:00:00
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journal_title：Neuropharmacology
pub_type： 杂志文章,评审
doi：10.1016/0028-3908(87)90064-5
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abstract：:The effects of thyrotropin-releasing hormone (TRH) were examined on the monosynaptic reflex and on the activity of motoneurons in the spinal cord of the neonatal rat to elucidate the mechanism of action of TRH and its ability to reverse the spinal depression caused by phencyclidine and ketamine. Phencyclidine (2-32 mi...
journal_title：Neuropharmacology
pub_type： 杂志文章
doi：10.1016/0028-3908(88)90061-5
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journal_title：Neuropharmacology
pub_type： 杂志文章
doi：10.1016/j.neuropharm.2017.11.002
更新日期：2018-02-01 00:00:00
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journal_title：Neuropharmacology
pub_type： 杂志文章
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更新日期：2000-09-01 00:00:00
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journal_title：Neuropharmacology
pub_type： 杂志文章
doi：10.1016/j.neuropharm.2006.05.006
更新日期：2006-09-01 00:00:00
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journal_title：Neuropharmacology
pub_type： 杂志文章
doi：10.1016/0028-3908(82)90024-7
更新日期：1982-05-01 00:00:00
abstract：:The basic unsolved questions concerning GABAA receptors are: "How many receptor subtypes exist?", "What subtypes are used by which types of neuron and where are they located on the cell?", and "What are the functions of the different subtypes?" As described in this Review, the cerebellum is an ideal vertebrate brain r...
journal_title：Neuropharmacology
pub_type： 杂志文章,评审
doi：10.1016/s0028-3908(96)00076-7
更新日期：1996-01-01 00:00:00
abstract：:The effect of the inhibition of aminopeptidase and enkephalinase A on the pain threshold of mice and rats was investigated, using bestatin and thiorphan as selective peptidase inhibitors. The results indicate that both enzymes are relevant to the catabolism of enkephalins in vivo; however, their simultaneous activatio...
journal_title：Neuropharmacology
pub_type： 杂志文章
doi：10.1016/0028-3908(83)90206-x
更新日期：1983-11-01 00:00:00
abstract：:Disruption of reproductive function is a hallmark of abuse of anabolic androgenic steroids (AAS) in female subjects. To understand the central actions of AAS, patch clamp recordings were made in estrous, diestrous and AAS-treated mice from gonadotropin releasing hormone (GnRH) neurons, neurons in the medial preoptic a...
journal_title：Neuropharmacology
pub_type： 杂志文章
doi：10.1016/j.neuropharm.2011.05.008
更新日期：2011-09-01 00:00:00
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journal_title：Neuropharmacology
pub_type： 杂志文章
doi：10.1016/j.neuropharm.2020.108175
更新日期：2020-09-01 00:00:00
abstract：:In view of the involvement of noradrenaline (NA) in the regulation of adrenocortical secretion, its role in the rise of plasma corticosterone following neural stimuli was evaluated in rats. The injection of the catecholamine neurotoxin 6-hydroxydopamine (6-OHDA) into the ventral noradrenergic bundle in the brain stem,...
journal_title：Neuropharmacology
pub_type： 杂志文章
doi：10.1016/0028-3908(88)90161-x
更新日期：1988-02-01 00:00:00
abstract：:Tropomyosin (Tm) in non-muscle cells is involved in stabilisation of the actin cytoskeleton. Some of the 40 isoforms described are found in the brain and exhibit spatial and developmental regulation. Non-muscle isoforms from the gamma Tm gene can be subdivided into three subsets of isoforms differing at the C-terminus...
journal_title：Neuropharmacology
pub_type： 杂志文章
doi：10.1016/j.neuropharm.2004.07.011
更新日期：2004-10-01 00:00:00
abstract：:The activity of tianeptine (2.5 and 5.0 mg/kg twice daily, i.p.) and of sertraline (5.0 mg/kg, twice daily, i.p.) were assessed in three animal models of depression. In the Behavioural Despair Test, acute treatment with sertraline or tianeptine (5.0 mg/kg) significantly reduced the immobility time. In the olfactory bu...
journal_title：Neuropharmacology
pub_type： 杂志文章
doi：10.1016/0028-3908(94)90160-0
更新日期：1994-08-01 00:00:00
abstract：:Remifentanil is commonly used clinically for perioperative pain relief, but it may induce postoperative hyperalgesia. Low doses of ketamine have remained a common choice in clinical practice, but the mechanisms of ketamine have not yet been fully elucidated. In this study, we examined the possible effects of ketamine ...
journal_title：Neuropharmacology
pub_type： 杂志文章
doi：10.1016/j.neuropharm.2019.107783
更新日期：2020-01-01 00:00:00
