Abstract：
:The effect of KN62 (1-[N,O-bis(5-isoquinolinesulphonyl)-N -methyl-L-tyrosyl]-4-phenylpiperazine), a putative inhibitor of Ca/calmodulin-dependent kinase II (Ca/CaM-K II), on glutamate release from isolated nerve-terminals (synaptosomes) was examined. The drug caused a potent inhibition of KCl- and 4-aminopyridine-evoked glutamate release from isolated nerve-terminals (synaptosomes). Examination of the effect of the inhibitor on Ca(2+)-influx revealed that the diminution of glutamate release could be attributed to a decrease in cytosolic Ca. A direct effect of KN62 on synaptosomal Ca(2+)-channels was confirmed in experiments where Ba, which does not support CaM-dependent processes, was used in place of Ca. Additionally, whole-cell patch-clamping of cerebellar granule neurones directly demonstrated inhibition of Ca-currents by KN62. We therefore suggest that, in cellular systems, conclusions based on the use of KN62 as a Ca/CaM-K II blocker may be ambiguous and should be viewed with caution unless the effect of the drug on Ca-influx has also been quantified. The effect of KN62 on Ca(2+)-influx appears to be specific to slowly-or non-inactivating conductances, and therefore presents KN62 as a potentially useful tool in this context.
journal_name
Neuropharmacologyjournal_title
Neuropharmacologyauthors
Sihra TS,Pearson HAdoi
10.1016/0028-3908(95)00051-7subject
Has Abstractpub_date
1995-07-01 00:00:00pages
731-41issue
7eissn
0028-3908issn
1873-7064pii
0028390895000517journal_volume
34pub_type
杂志文章abstract：:Marijuana use in adolescence, but not adulthood, may permanently impair cognitive functioning and increase the risk of developing schizophrenia. Cortical oscillations are patterns of neural network activity implicated in cognitive processing, and are abnormal in patients with schizophrenia. We have recently reported t...
journal_title：Neuropharmacology
pub_type： 杂志文章
doi：10.1016/j.neuropharm.2014.07.006
更新日期：2014-11-01 00:00:00
abstract：:Suicide is a major global problem, claiming more than 800,000 lives annually. The neurobiological changes that underlie suicidal ideation and behavior are not fully understood. Suicidal patients have been shown to display elevated levels of inflammation both in the central nervous system and the peripheral blood. A gr...
journal_title：Neuropharmacology
pub_type： 杂志文章,评审
doi：10.1016/j.neuropharm.2016.01.034
更新日期：2017-01-01 00:00:00
abstract：:Nicotinic receptors containing the alpha7 gene product are among the most abundant in the nervous system. Because of their widespread distribution and high relative permeability to calcium, the receptors regulate a diverse array of cellular events. On chick ciliary neurons the receptors are concentrated on somatic spi...
journal_title：Neuropharmacology
pub_type： 杂志文章
doi：10.1016/s0028-3908(00)00132-5
更新日期：2000-10-01 00:00:00
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journal_title：Neuropharmacology
pub_type： 杂志文章
doi：10.1016/0028-3908(87)90171-7
更新日期：1987-10-01 00:00:00
abstract：:The acute effects of simvastatin lactone (lipophilic) and simvastatin acid (hydrophilic) on transient focal ischemia were assessed using the isolated guinea pig brain maintained in vitro by arterial perfusion. This new model of cerebral ischemia allows the assessment of the very early phase of the ischemic process, wi...
journal_title：Neuropharmacology
pub_type： 杂志文章
doi：10.1016/j.neuropharm.2011.01.003
更新日期：2011-05-01 00:00:00
abstract：:Based on significant amount of evidence, it is now generally believed, that one underlying cause for neurodegenerative diseases, could be dysregulation in inflammatory processes. The actual mechanisms involved are not yet well understood. Several studies have demonstrated the potent analgesic and anti-inflammatory act...
journal_title：Neuropharmacology
pub_type： 杂志文章
doi：10.1016/j.neuropharm.2010.11.004
更新日期：2011-02-01 00:00:00
abstract：:Opioid drugs such as heroin interact directly with opioid receptors whilst other addictive drugs, including marijuana, alcohol and nicotine indirectly activate endogenous opioid systems to contribute to their rewarding properties. The opioid system therefore plays a key role in addiction neurobiology and continues to ...
journal_title：Neuropharmacology
pub_type： 杂志文章,评审
doi：10.1016/j.neuropharm.2008.07.033
更新日期：2009-01-01 00:00:00
abstract：:The anticonvulsant action and the long-term effects on learning, memory and behavior of the new generation antiepileptic drug gabapentin (GBP) were investigated in immature animals. Kainic acid (KA) was administered to rats on postnatal day (P) 35. Animals were treated with GBP or saline from P36 to P75 and spontaneou...
journal_title：Neuropharmacology
pub_type： 杂志文章
doi：10.1016/s0028-3908(00)00103-9
更新日期：2001-01-01 00:00:00
abstract：:A new in vivo pharmacological method for the quantitative evaluation of alpha 1-adrenoceptor agonists and antagonists has been developed. It consists of recording the myoclonic twitch activity (MTA) of the suprahyoideal muscle of rats anesthetized with urethane. In these animals, the isomers of amphetamine elicited my...
journal_title：Neuropharmacology
pub_type： 杂志文章
doi：10.1016/0028-3908(86)90175-9
更新日期：1986-05-01 00:00:00
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journal_title：Neuropharmacology
pub_type： 杂志文章
doi：10.1016/0028-3908(92)90092-4
更新日期：1992-05-01 00:00:00
abstract：:The cannabinoid receptor CB2 plays a significant role in the regulation of immune function whereas neuronal expression remains a subject of contention. Multiple studies have described CB2 in retina and a recent study showed that CB2 deletion altered retinal visual processing. We revisited CB2 expression using immunohi...
journal_title：Neuropharmacology
pub_type： 杂志文章
doi：10.1016/j.neuropharm.2018.08.007
更新日期：2018-10-01 00:00:00
abstract：:In the present study we have examined the role of presynaptic group I metabotropic glutamate (mGlu) receptors in the control of neuronal glutamate release using rat forebrain slices pre-loaded with [(3)H]D-aspartate. We have also addressed the question of which group I mGlu receptor subtype, mGlu(1) or mGlu(5), mediat...
journal_title：Neuropharmacology
pub_type： 杂志文章
doi：10.1016/s0028-3908(99)00223-3
更新日期：2000-07-10 00:00:00
abstract：:The potential contributions of dysregulation of the brain's histaminergic modulatory system to neuropsychiatric disease, and the potential of histamine-targeting medications as therapeutic agents, are gradually coming into focus. The H3R receptor, which is expressed primarily in the central nervous system, is a promis...
journal_title：Neuropharmacology
pub_type： 杂志文章,评审
doi：10.1016/j.neuropharm.2015.08.019
更新日期：2016-07-01 00:00:00
abstract：:Opioids are thought to increase the excitability of hippocampal pyramidal cells by decreasing release of neurotransmitter from inhibitory interneurons. This study compared the actions of the opioid agonist normorphine, and the GABA receptor antagonist bicuculline, on the responses of CA1 pyramidal cells to afferent st...
journal_title：Neuropharmacology
pub_type： 杂志文章
doi：10.1016/0028-3908(89)90152-4
更新日期：1989-07-01 00:00:00
abstract：:The kynurenine pathway of tryptophan metabolism has been implicated in brain function, immunoregulation, anti-microbial mechanisms and pregnancy. Some of these actions are due to depletion of tryptophan and others to the formation of biologically active metabolites. This review focuses on the roles of the kynurenine p...
journal_title：Neuropharmacology
pub_type： 杂志文章,评审
doi：10.1016/j.neuropharm.2016.02.029
更新日期：2017-01-01 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：:Long-term potentiation (LTP) resembles memory in that it is initially unstable and then, over about 30 min, becomes increasingly resistant to disruption. Here we present an hypothesis to account for this initial consolidation effect and consider implications that follow from it. Anatomical studies indicate that LTP is...
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
abstract：:The objective of this study was to compare nAChR-mediated neurotransmitter release from slices of rat striatum, frontal cortex and hippocampus following chronic (-)-nicotine (Nic) administration (tartrate salt, 2 mg/kg twice daily for 10 days). Binding studies were also conducted to measure changes in receptor density...
journal_title：Neuropharmacology
pub_type： 杂志文章
doi：10.1016/s0028-3908(02)00166-1
更新日期：2002-10-01 00:00:00
abstract：:[3H]Paroxetine is a highly selective ligand for the 5-hydroxytryptamine transporter complex and the specific binding of this ligand to membrane fractions from cerebral cortex or hippocampus was studied in rats treated with specific inhibitors of the uptake of 5-hydroxytryptamine and monoamine oxidase inhibitors. The K...
journal_title：Neuropharmacology
pub_type： 杂志文章
doi：10.1016/0028-3908(87)90252-8
更新日期：1987-08-01 00:00:00
abstract：:Using juvenile rat brain slices, we examined the possibility that strychnine-sensitive receptors for glycine-like amino acids contributed to synaptic inhibition in ventrobasal thalamus, where gamma-aminobutyrate (GABA) is the prevalent inhibitory transmitter. Ventrobasal nuclei showed staining for antibodies against a...
journal_title：Neuropharmacology
pub_type： 杂志文章
doi：10.1016/j.neuropharm.2005.03.013
更新日期：2005-09-01 00:00:00
abstract：:The bed nucleus of the stria terminalis (BNST) is a group of inter-connected subnuclei that play critical roles in stress-reward interactions. An interesting feature of this brain region is the massive noradrenergic input that it receives. Important roles for norepinephrine in this region have been documented in a num...
journal_title：Neuropharmacology
pub_type： 杂志文章,评审
doi：10.1016/j.neuropharm.2013.02.013
更新日期：2013-07-01 00:00:00
abstract：:Mice deficient in the microtubule stabilizing protein STOP (stable tubule only polypeptide) show synaptic plasticity anomalies in hippocampus, dopamine hyper-reactivity in the limbic system and severe behavioral deficits. Some of these disturbances are alleviated by long-term antipsychotic treatment. Therefore, this m...
journal_title：Neuropharmacology
pub_type： 杂志文章
doi：10.1016/j.neuropharm.2007.03.015
更新日期：2007-06-01 00:00:00
abstract：:BMS-763534 is a potent (CRF(1) IC(50) = 0.4 nM) and selective (>1000-fold selectivity vs. all other sites tested) CRF(1) receptor antagonist (pA2 = 9.47 vs. CRF(1)-mediated cAMP production in Y79 cells). BMS-763534 accelerated the dissociation of (125)I-o-CRF from rat frontal cortex membrane CRF(1) receptors consisten...
journal_title：Neuropharmacology
pub_type： 杂志文章
doi：10.1016/j.neuropharm.2012.10.025
更新日期：2013-04-01 00:00:00
abstract：:N-Methyl-D-aspartate (NMDA) receptors are important CNS target sites of alcohols, but the site and mechanism of action of alcohols on NMDA receptors remains unclear. In CHO-K1 cells transfected with NR1/NR2B NMDA receptor subunits, ethanol inhibited NMDA-activated current with an IC(50) of 138 mM. Truncation of the in...
journal_title：Neuropharmacology
pub_type： 杂志文章
doi：10.1016/s0028-3908(00)00067-8
更新日期：2000-07-24 00:00:00
abstract：:The so-called generalized polarization (GP) of the fluorescent probe Laurdan and the steady-state fluorescence anisotropy of the probe diphenylhexatriene (DPH) and its phenylpropionic derivative (PA-DPH) were used to study the effects of several organochlorine insecticides of the chlorophenylethane, chlorinated cycloh...
journal_title：Neuropharmacology
pub_type： 杂志文章
doi：10.1016/s0028-3908(99)00194-x
更新日期：2000-04-03 00:00:00
abstract：:Dural plasma extravasation produced by electrical stimulation of the trigeminal ganglion was measured in rats and the concomitant expression of c-fos mRNA produced in the trigeminal nucleus caudalis (NtV) was measured using in situ hybridization techniques. The non-peptide NK1 receptor selective antagonist CP-99,994 (...
journal_title：Neuropharmacology
pub_type： 杂志文章
doi：10.1016/0028-3908(94)00153-j
更新日期：1995-03-01 00:00:00
abstract：:Recently it has been reported that "I(f) channel blockers", which block the hyperpolarization-activated inward current (I(f)) in heart sino atrial node cells, also block the hyperpolarization-activated inward current (I(h)) in other tissues. Here we compared the effects of one of these agents, ZD7288 [4-(N-ethyl-N-phe...
journal_title：Neuropharmacology
pub_type： 杂志文章
doi：10.1016/s0028-3908(99)00207-5
更新日期：2000-04-27 00:00:00
abstract：:The effects of prostaglandin (PG) E(1) on NO neurotoxicity were examined using rat cultured spinal neurons. Rat cultured spinal neurons exposed to the NO donor, 2,2'-(hydroxynitrosohydrazono) bis-ethanamine (NOC18), showed neurotoxic effects that were accompanied by apoptotic nuclear change, free radical generation, a...
journal_title：Neuropharmacology
pub_type： 杂志文章
doi：10.1016/s0028-3908(02)00020-5
更新日期：2002-04-01 00:00:00
abstract：:Neural sensorimotor gating mechanisms prevent the interruption of ongoing information processing routines by ensuing stimuli to permit mental integration and adaptive behavior. Prepulse inhibition (PPI), an operational measure of sensorimotor gating, is now being investigated using murine models to exploit transgenic ...
journal_title：Neuropharmacology
pub_type： 杂志文章
doi：10.1016/s0028-3908(00)00030-7
更新日期：2000-08-23 00:00:00
abstract：:Rats were trained to recognize a discriminative stimulus (DS) elicited by the dopamine D(2)/D(3) receptor agonist, PD128,907 (0.16 mg/kg, i.p.), which suppressed frontocortical release of dopamine (DA) but not 5-HT. The selective 5-HT1A receptor agonists, 8-OH-DPAT and flesinoxan, dose-dependently generalized to PD128...
journal_title：Neuropharmacology
pub_type： 杂志文章
doi：10.1016/s0028-3908(01)00022-3
更新日期：2001-06-01 00:00:00
