Abstract：
:This study investigated the structure-activity relationships and kinetic properties of a library of kynurenate analogues as inhibitors of 3H-L-glutamate transport into rat forebrain synaptic vesicles. The lack of inhibitory activity observed with the majority of the monocyclic pyridine derivatives suggested that the second aromatic ring of the quinoline-based compounds played a significant role in binding to the transporter. A total of two kynurenate derivatives, xanthurenate and 7-chloro-kynurenate, differing only in the carbocyclic ring substituents, were identified as potent competitive inhibitors, exhibiting Ki values of 0.19 and 0.59 mM, respectively. The Km value for L-glutamate was found to be 2.46 mM. Parallel experiments demonstrated that while none of the kynurenate analogues tested effectively inhibited the synaptosomal transport of 3H-D-aspartate, some cross-reactivity was observed with the EAA ionotropic receptors. Molecular modeling studies were carried out with the identified inhibitors and glutamate in an attempt to preliminarily define the pharmacophore of the vesicular transporter. It is hypothesized that the ability of the kynurenate analogues to bind to the transporter may be tied to the capacity of the quinoline carbocyclic ring to mimic the negative charge of the gamma-carboxylate of glutamate. A total of two low energy solution conformers of glutamate were identified that exhibited marked functional group overlap with the most potent inhibitor, xanthurenate. These results help to further refine the pharmacological specificity of the glutamate binding site on the vesicular transporter and identify a series of inhibitors with which to investigate transporter function.
journal_name
Neuropharmacologyjournal_title
Neuropharmacologyauthors
Bartlett RD,Esslinger CS,Thompson CM,Bridges RJdoi
10.1016/s0028-3908(98)00080-xsubject
Has Abstractpub_date
1998-07-01 00:00:00pages
839-46issue
7eissn
0028-3908issn
1873-7064pii
S002839089800080Xjournal_volume
37pub_type
杂志文章abstract：:Electrical stimulation of the optic nerve evoked two positive waves with short latency, followed by a large negative wave in the suprachiasmatic nucleus of slices of hypothalamus of the rat. The latency to peak of the two positive waves and the large negative wave were 2.7 +/- 0.1, 6.1 +/- 0.1 and 10.3 +/- 0.5 msec, r...
journal_title：Neuropharmacology
pub_type： 杂志文章
doi：10.1016/0028-3908(86)90235-2
更新日期：1986-04-01 00:00:00
abstract：:Physical exercise has become a potentially beneficial therapy for reducing neurodegeneration symptoms in Alzheimer's disease. Previous studies have shown that cognitive deterioration, anxiety and the startle response observed in 7-month-old 3xTg-AD mice were ameliorated after 6 months of free access to a running wheel...
journal_title：Neuropharmacology
pub_type： 杂志文章
doi：10.1016/j.neuropharm.2014.01.037
更新日期：2014-06-01 00:00:00
abstract：:In the solitary tract nucleus, neuronal responsiveness to synaptic input from peripheral afferent fibres has been found to decrease as the frequency of that input is increased. The present study investigated the possibility that glycine and gamma-aminobutyric acid (GABA) are (1) involved in this phenomenon of "frequen...
journal_title：Neuropharmacology
pub_type： 杂志文章
doi：10.1016/0028-3908(91)90149-6
更新日期：1991-03-01 00:00:00
abstract：:Human genetic variation in the gene CACNA1C, which codes for the alpha-1c subunit of Cav1.2 L-type calcium channels (LTCCs), has been broadly associated with enhanced risk for neuropsychiatric disorders including major depression, bipolar and schizophrenia. Little is known about the specific neural circuits through wh...
journal_title：Neuropharmacology
pub_type： 杂志文章
doi：10.1016/j.neuropharm.2018.08.033
更新日期：2019-01-01 00:00:00
abstract：:Acute morphine administration produces analgesia and reward, but prolonged use may lead to analgesic tolerance in patients chronically treated for pain and to compulsive intake in opioid addicts. Moreover, long-term exposure may induce physical dependence, manifested as somatic withdrawal symptoms in the absence of th...
journal_title：Neuropharmacology
pub_type： 杂志文章
doi：10.1016/j.neuropharm.2007.10.015
更新日期：2008-03-01 00:00:00
abstract：:In the current study, we investigated the effect of the activation of the alpha-7 nicotinic acetylcholine receptor (α7 nAchR) on dextran sulphate sodium (DSS)-induced colitis and referred mechanical hyperalgesia in mice. Colitis was induced in CD1 male mice through the intake of 4% DSS in tap water for 7 days. Control...
journal_title：Neuropharmacology
pub_type： 杂志文章
doi：10.1016/j.neuropharm.2012.06.004
更新日期：2012-10-01 00:00:00
abstract：:Recently we reported that fluoxetine (10 mg/kg) improves functional recovery by attenuating blood spinal cord barrier (BSCB) disruption after spinal cord injury (SCI). Here we investigated whether a low-dose of fluoxetine (1 mg/kg) and vitamin C (100 mg/kg), separately not possessing any protective effect, prevents BS...
journal_title：Neuropharmacology
pub_type： 杂志文章
doi：10.1016/j.neuropharm.2016.05.018
更新日期：2016-10-01 00:00:00
abstract：:Efforts to translate sub-anesthetic ketamine infusions into widespread clinical use have centered around developing medications with comparable neurobiological activity, but with attenuated psychoactive effects so as to minimize the risk of behavioral toxicity and abuse liability. Converging lines of research, however...
journal_title：Neuropharmacology
pub_type： 杂志文章,随机对照试验
doi：10.1016/j.neuropharm.2018.01.005
更新日期：2018-11-01 00:00:00
abstract：:The present study was designed to clarify whether α2-adrenoceptors of the basolateral amygdala (BLA) are involved in nicotine-induced anxiogenic-like behaviours. Adult male Wistar rats were bilaterally cannulated in the BLA and anxiety-like behaviours were assessed in an elevated plus maze (EPM) task. Systemic intrape...
journal_title：Neuropharmacology
pub_type： 杂志文章
doi：10.1016/j.neuropharm.2016.02.010
更新日期：2016-06-01 00:00:00
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journal_title：Neuropharmacology
pub_type： 杂志文章
doi：10.1016/0028-3908(86)90014-6
更新日期：1986-08-01 00:00:00
abstract：:We have recently reported that intraperitoneal (i.p.) injection of thymulin at low doses (50 ng) resulted in thermal and mechanical hyperalgesia and upregulation of the level of interleukin-1beta in the liver. In this study, we demonstrate that such injections of thymulin result in a significant elevation in the level...
journal_title：Neuropharmacology
pub_type： 杂志文章
doi：10.1016/s0028-3908(99)00247-6
更新日期：2000-07-10 00:00:00
abstract：:Stimulation of cannabinoid CB1 receptors or inhibition of nitric oxide synthase (NOS) in the dorsolateral periaqueductal gray (dlPAG) decreases anxiety-like behavior. Moreover, activation of CB1 receptors attenuates flight responses induced by nitric oxide (NO) donors in the dlPAG, suggesting that endocannabinoids and...
journal_title：Neuropharmacology
pub_type： 杂志文章
doi：10.1016/j.neuropharm.2013.07.008
更新日期：2013-12-01 00:00:00
abstract：:The psychostimulant drug amphetamine increases extracellular monamines in the brain acting on neurotransmitter transporters, especially the dopamine transporter. Mediated by this plasmalemmal pump, amphetamine does not only induce release but also charge transfer which might be involved in the release mechanism. To st...
journal_title：Neuropharmacology
pub_type： 杂志文章
doi：10.1016/j.neuropharm.2003.09.007
更新日期：2004-02-01 00:00:00
abstract：:Midbrain dopamine neurons play a key role in goal-directed behaviour as well as in some psychiatric disorders. Recent studies have provided electrophysiological, anatomical and biochemical evidence that the lateral habenula (LHb) exerts strong inhibitory control over midbrain dopamine neurons. However, the behavioural...
journal_title：Neuropharmacology
pub_type： 杂志文章
doi：10.1016/j.neuropharm.2012.07.032
更新日期：2012-11-01 00:00:00
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journal_title：Neuropharmacology
pub_type： 杂志文章
doi：10.1016/0028-3908(84)90105-9
更新日期：1984-07-01 00:00:00
abstract：:Ginsenoside Rg1 (Rg1) acts as a neuroprotective agent against various insults, however, the underlying mechanism has not been fully elucidated yet. Here, we report that Rg1 protects primary rat cerebrocortical neurons against β-amyloid peptide₂₅₋₃₅ (Aβ₂₅₋₃₅) injury via estrogen receptor α (ERα) and glucocorticoid rece...
journal_title：Neuropharmacology
pub_type： 杂志文章
doi：10.1016/j.neuropharm.2012.04.005
更新日期：2012-09-01 00:00:00
abstract：:The influence of the subunit composition of human GABA(A) receptors upon the GABA-modulatory properties of 5alpha-pregnan-3alpha-ol-20-one (5alpha,3alpha) has been examined using the Xenopus laevis oocyte expression system and the two electrode voltage-clamp technique. Steroid potency (EC(50)) is modestly influenced b...
journal_title：Neuropharmacology
pub_type： 杂志文章
doi：10.1016/s0028-3908(02)00172-7
更新日期：2002-09-01 00:00:00
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journal_title：Neuropharmacology
pub_type： 杂志文章
doi：10.1016/0028-3908(95)00180-8
更新日期：1996-02-01 00:00:00
abstract：:Propofol has been shown to attenuate brain injury in experimental ischemia models, but few studies have focused on the direct effect of propofol on mitochondrial dysfunction. In this study, we observed the effects of propofol on multiple aspects of mitochondrial dysfunction by studying the mitochondria isolated from r...
journal_title：Neuropharmacology
pub_type： 杂志文章
doi：10.1016/j.neuropharm.2013.08.029
更新日期：2014-02-01 00:00:00
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journal_title：Neuropharmacology
pub_type： 杂志文章
doi：10.1016/j.neuropharm.2009.10.002
更新日期：2010-02-01 00:00:00
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journal_title：Neuropharmacology
pub_type： 杂志文章
doi：10.1016/0028-3908(84)90060-1
更新日期：1984-11-01 00:00:00
abstract：:The hypothalamic-pituitary-adrenal (HPA) axis is activated by a wide range of stimuli, including drugs. Here we report that in male rats, a dose of sodium butyrate (NaBu) that is typically used to inhibit histone deacetylation (1200 mg/kg) increased the peripheral levels of HPA hormones and glucose. In a further exper...
journal_title：Neuropharmacology
pub_type： 杂志文章
doi：10.1016/j.neuropharm.2013.10.031
更新日期：2014-04-01 00:00:00
abstract：:Alcohol use disorder (AUD) is a serious public health problem that results in tremendous social, legal and medical costs to society. Unlike other addictive drugs, there is no specific molecular target for ethanol (EtOH). Here, we report a novel molecular target that mediates EtOH effects at concentrations below those ...
journal_title：Neuropharmacology
pub_type： 杂志文章
doi：10.1016/j.neuropharm.2019.01.021
更新日期：2019-05-01 00:00:00
abstract：:It is known that changes in gene expression within the nucleus accumbens (NAc) occur during cocaine dependence development. However, identification of specific genes involved in cocaine conditioning awaits further investigation. We conducted a high throughput gene expression profile analysis of the NAc, during differe...
journal_title：Neuropharmacology
pub_type： 杂志文章
doi：10.1016/j.neuropharm.2009.06.040
更新日期：2010-01-01 00:00:00
abstract：:We have used whole-cell patch clamp electrophysiology to characterise the actions of the P2 antagonist, cibacron blue, on the rat recombinant P2X4 receptor, stably expressed in human embryonic kidney 293 (HEK293) cells. In single cells, adenosine triphosphate (ATP) evoked inward currents, but the response was subject ...
journal_title：Neuropharmacology
pub_type： 杂志文章
doi：10.1016/s0028-3908(98)00153-1
更新日期：1998-12-01 00:00:00
abstract：:Intrapritoneal injection of N-ethoxycarbonyl-2-ethoxy-1,2-dihydroquinoline (EEDQ) to rats significantly reduced the density of alpha 1- and alpha 2-adrenoceptors in the cerebral cortex, without affecting beta-adrenoceptors. A single dose of EEDQ markedly accelerated the development of downregulation of beta-adrenocept...
journal_title：Neuropharmacology
pub_type： 杂志文章
doi：10.1016/0028-3908(90)90169-r
更新日期：1990-05-01 00:00:00
abstract：:The elevation of extracellular 5-HT after systemic administration of 5-HT reuptake inhibiting drugs is strongly potentiated by agents capable of blocking 5-HT1A autoreceptors in the midbrain raphe. The present in vivo microdialysis study was aimed at assessing the relative importance of 5-HT reuptake inhibition versus...
journal_title：Neuropharmacology
pub_type： 杂志文章
doi：10.1016/s0028-3908(97)00050-6
更新日期：1997-04-01 00:00:00
abstract：:The effect of clonidine (0.1 mg/kg, i.p.), as a three-injection course, on behaviour in the forced swimming test was studied in rats injected intracerebroventricularly (i.c.v.) with 150 micrograms 5,7-dihydroxy-tryptamine (5,7-DHT) to destroy serotonin (5-HT) neurones or treated with 100 mg/kg (i.p.) (+/-)-sulpiride o...
journal_title：Neuropharmacology
pub_type： 杂志文章
doi：10.1016/0028-3908(92)90064-v
更新日期：1992-04-01 00:00:00
abstract：:The rat hemisected spinal cord preparation was used to assess the role of different adrenoceptor subtypes on the modulation of nociceptive reflexes. These were elicited by trains of high intensity electrical stimuli delivered to a lumbar dorsal root. Responses were recorded from the corresponding ventral root in AC- a...
journal_title：Neuropharmacology
pub_type： 杂志文章
doi：10.1016/s0028-3908(01)00117-4
更新日期：2001-12-01 00:00:00
abstract：:Behavioral flexibility is in close proximity to dentate gyrus (DG) function and long-term depression (LTD), but the role of DG LTD in behavioral flexibility has hitherto been unexplored. Although the functions of alpha-Ca2+/calmodulin-dependent protein kinase II (CaMKII) have been studied extensively, the role of βCaM...
journal_title：Neuropharmacology
pub_type： 杂志文章
doi：10.1016/j.neuropharm.2016.12.013
更新日期：2017-04-01 00:00:00
