Abstract：
:The kinetics of synaptic currents is largely determined by the postsynaptic receptor gating and the concentration time course of synaptic neurotransmitter. While the analysis of current responses to rapid agonist application provides the means to study the ligand-gated receptor gating, no direct tools are available to measure the neurotransmitter transient at GABAergic and glutamatergic synapses. Several lines of evidence indicate that the synaptic agonist transient is very brief suggesting that the activation of postsynaptic receptors occurs in conditions of extreme non-equilibrium. Such a dynamic pattern of activation has a crucial impact not only on the kinetics of synaptic currents but also on their susceptibility to pharmacological modulation. Thus, changes in the synaptic agonist waveform due to, for example modulation of the release machinery or uptake system may considerably alter both kinetics and pharmacology of synaptic currents. The use of modifiers of GABA(A) receptor gating and low-affinity antagonists provides a tool to estimate the time course of the agonist transient revealing that synaptic neurotransmitter is not saturating and that the agonist clearance occurs at a sub-millisecond time scale. It is proposed that dynamic conditions of synaptic receptor activation assure a broad spectrum of performance rendering the synapse extremely susceptible to a variety of modulatory processes.
journal_name
Neuropharmacologyjournal_title
Neuropharmacologyauthors
Mozrzymas JWdoi
10.1016/j.neuropharm.2004.07.003subject
Has Abstractpub_date
2004-12-01 00:00:00pages
945-60issue
7eissn
0028-3908issn
1873-7064pii
S0028390804001893journal_volume
47pub_type
杂志文章,评审abstract：:How does an agonist activate a receptor? In this article I consider the activation process in muscle nicotinic acetylcholine receptors (AChRs), a prototype for understanding the energetics of binding and gating in other ligand-gated ion channels. Just as movements that generate gating currents activate voltage-gated i...
journal_title：Neuropharmacology
pub_type： 杂志文章,评审
doi：10.1016/j.neuropharm.2014.10.004
更新日期：2015-09-01 00:00:00
abstract：:Gliomas are the leading cause of cancer-related mortality worldwide, and the incidence is increasing. Because gliomas often become resistant to radiation treatment, it is urgent to develop novel therapeutic methods that are more effective and less toxic than current therapies so as to enhance patient survival and qual...
journal_title：Neuropharmacology
pub_type： 杂志文章
doi：10.1016/j.neuropharm.2014.05.009
更新日期：2015-02-01 00:00:00
abstract：:Recent observations from synaptosome preparations have questioned the tetrodotoxin (TTX) insensitivity of nicotine-evoked release in the striatum, a characteristic previously considered diagnostic of presynaptically located nicotinic acetylcholine receptors (nAChRs). Therefore, we have undertaken a comparison of nicot...
journal_title：Neuropharmacology
pub_type： 杂志文章
doi：10.1016/s0028-3908(96)00117-7
更新日期：1996-01-01 00:00:00
abstract：:Nitric oxide modulates pain development. However, there is no evidence on the effect of nitroxyl (HNO/NO⁻) in nociception. Therefore, we addressed whether nitroxyl inhibits inflammatory hyperalgesia and its mechanism using the nitroxyl donor Angeli's salt (AS; Na₂N₂O₃). Mechanical hyperalgesia was evaluated using a mo...
journal_title：Neuropharmacology
pub_type： 杂志文章
doi：10.1016/j.neuropharm.2013.03.009
更新日期：2013-08-01 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：:The effect of various doses of tianeptine on the extracellular concentrations of dopamine was studied in the striatum and nucleus accumbens of the rat. At 5 (but not 2.5) mg/kg intraperitoneally, tianeptine increased the extracellular dopamine only in the nucleus accumbens. At 10 mg/kg, the effect was also seen in the...
journal_title：Neuropharmacology
pub_type： 杂志文章
doi：10.1016/0028-3908(92)90171-k
更新日期：1992-03-01 00:00:00
abstract：:Stem cell research offers enormous potential for treating many diseases of the nervous system. At present, therapeutic strategies in stem cell research segregate into two approaches: cell transplantation or endogenous cell stimulation. Realistically, future cell therapies will most likely involve a combination of thes...
journal_title：Neuropharmacology
pub_type： 杂志文章,评审
doi：10.1016/j.neuropharm.2009.10.005
更新日期：2010-05-01 00:00:00
abstract：:Administration of serotonin-enhancing drugs induces a distinctive behavioral syndrome in rodents. We previously reported that mice with a targeted disruption of the serotonin transporter (SERT) display some of these behaviors spontaneously, in the absence of drug. In the current studies, we assessed the drug-induced s...
journal_title：Neuropharmacology
pub_type： 杂志文章
doi：10.1016/j.neuropharm.2007.07.009
更新日期：2007-10-01 00:00:00
abstract：:Selective central benzodiazepine agonists, such as clonazepam, are known to modify serotonin and 5-hydroxyindoleacetic content in the brain. In order to further study the effect of this benzodiazepine on serotonin turnover rate, rats received clonazepam, 10 mg/kg for 10 days, and the concentrations of serotonin and 5-...
journal_title：Neuropharmacology
pub_type： 杂志文章
doi：10.1016/0028-3908(95)00103-d
更新日期：1995-10-01 00:00:00
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
pub_type： 杂志文章
doi：10.1016/j.neuropharm.2016.10.010
更新日期：2017-02-01 00:00:00
abstract：:Inhibition of calcium-evoked [3H]ACh release by different classes of calcium channel blockers was compared among calcium-naive synaptosomes from chick, frog and rat forebrain tissues. In all three species, [3H]ACh release was insensitive to nifedipine (0.03-3 microM) but was completely inhibited by cadmium (IC50 range...
journal_title：Neuropharmacology
pub_type： 杂志文章
doi：10.1016/0028-3908(92)90181-n
更新日期：1992-03-01 00:00:00
abstract：:The present study used a radiotelemetric method to compare the muscle relaxant, hypothermic and locomotor depressant actions of the imidazopyridine zolpidem, with those of the benzodiazepines lorazepam and diazepam. Rats, n=7 per group, were divided into 3 dose-dependent treatment groups (highest, middle, and lowest)....
journal_title：Neuropharmacology
pub_type： 杂志文章
doi：10.1016/s0028-3908(00)00196-9
更新日期：2001-04-01 00:00:00
abstract：:We studied the effect of YM-39558, orotic acid ethylester, in a focal cerebral ischemia model in anesthetized cats. YM-39558 has good permeability across the blood brain barrier, and in the brain is hydrolyzed to orotic acid, the main active substance. Cats were subjected to permanent occlusion of the middle cerebral ...
journal_title：Neuropharmacology
pub_type： 杂志文章
doi：10.1016/s0028-3908(98)00008-2
更新日期：1998-01-01 00:00:00
abstract：:Brain inosine and hypoxanthine were measured in mice at intervals following the intraperitoneal injection of pentylenetetrazol (PTZ), 100 mg/kg. These purines increased only after myoclonic jerks appeared and were maximal at the time of tonic hindlimb extension. Phenytoin and phenobarbital, which prevent tonic hindlim...
journal_title：Neuropharmacology
pub_type： 杂志文章
doi：10.1016/0028-3908(83)90161-2
更新日期：1983-05-01 00:00:00
abstract：:The hypoactivity in rats induced by small doses of apomorphine, injected bilaterally into the nucleus accumbens area of the brain, could be antagonized by pretreatment with the neuroleptic-like neuropeptide des-enkephalin-gamma-endorphin (DE gamma E, beta-endorphin 6-17) as well as with the neuroleptic drugs haloperid...
journal_title：Neuropharmacology
pub_type： 杂志文章
doi：10.1016/0028-3908(82)90168-x
更新日期：1982-11-01 00:00:00
abstract：:Following its binding to somatodendritic receptors, the neuropeptide neurotensin (NT) internalizes via a clathrin-mediated process. In the present study, we investigated whether NT also internalizes presynaptically using synaptosomes from rat neostriatum, a region in which NT1 receptors are virtually all presynaptic. ...
journal_title：Neuropharmacology
pub_type： 杂志文章
doi：10.1016/s0028-3908(02)00054-0
更新日期：2002-06-01 00:00:00
abstract：:The potential role of N-linked glycosylation of the human type 1alpha metabotropic glutamate (mGlu1alpha) receptor was studied in a recombinant, inducible expression system, where receptor expression was induced in the absence and presence of tunicamycin. In the absence of tunicamycin the mGlu1alpha receptor appeared ...
journal_title：Neuropharmacology
pub_type： 杂志文章
doi：10.1016/s0028-3908(99)00099-4
更新日期：1999-10-01 00:00:00
abstract：:Lesions of the ventral hippocampus (VH) in neonatal rats result in post-pubertal alterations in a number of cognitive, social and motor behaviors that bear some analogy to schizophrenia. Increased sensitivity to stress and psychostimulants and prefrontal functional changes in the lesioned animals suggest an involvemen...
journal_title：Neuropharmacology
pub_type： 杂志文章
doi：10.1016/j.neuropharm.2003.08.001
更新日期：2004-01-01 00:00:00
abstract：:4-Alkylated analogues of homoibotenic acid (HIBO) have previously shown high potency and selectivity at ionotropic and metabotropic glutamic acid receptor (iGluR and mGluR) subtypes. Compounds with different selectivity profiles are valuable pharmacological tools for neuropharmacological studies, and the series of 4-a...
journal_title：Neuropharmacology
pub_type： 杂志文章
doi：10.1016/j.neuropharm.2005.05.007
更新日期：2005-01-01 00:00:00
abstract：:The study investigated the interaction between phencyclidine (PCP) and morphine in affecting the levels of met-enkephalin, dopamine, DOPAC and HVA in mice. Morphine 5 mg/kg alone and PCP 10 mg/kg alone failed to change the levels of met-enkephalin in the midbrain and striatum. However, PCP in combination with morphine...
journal_title：Neuropharmacology
pub_type： 杂志文章
doi：10.1016/0028-3908(85)90016-4
更新日期：1985-08-01 00:00:00
abstract：:Cyclosporine, a calcineurin inhibitor, significantly enhances spontaneous acetylcholine release after a brief tetanus and potentiates the effect of phorbol 12,13-dibutyrate. Both actions are prevented by the protein kinase C inhibitor, bisindolylmaleimide iodide. Protein kinase C and calcineurin thus play important ro...
journal_title：Neuropharmacology
pub_type： 杂志文章
doi：10.1016/s0028-3908(98)00178-6
更新日期：1999-01-01 00:00:00
abstract：:Opioids evoke analgesia through activation of opioid receptors (predominantly the μ opioid receptor) in the central nervous system. Opioid receptors are abundant in multiple regions of the central nervous system and the peripheral nervous system including enteric neurons. Opioid-related adverse effects such as constip...
journal_title：Neuropharmacology
pub_type： 杂志文章,评审
doi：10.1016/j.neuropharm.2017.12.032
更新日期：2018-03-15 00:00:00
abstract：:The effects of intravenously administered mephenesin, tolperisone, baclofen, diazepam and midazolam on reflex activity were studied in unanesthetized spinal cats. Monosynaptic, as well as polysynaptic ventral root reflexes, the dorsal root potential and the dorsal root reflex were recorded simultaneously from L6-S1 se...
journal_title：Neuropharmacology
pub_type： 杂志文章
doi：10.1016/0028-3908(89)90053-1
更新日期：1989-02-01 00:00:00
abstract：:Microglial cells killed neurons damaged following incubation with sub-lethal concentrations of peptides derived from either the human prion protein (HuPrP82-146) or amyloid-beta1-42 (a peptide found in Alzheimer's disease). HuPrP82-146 or amyloid-beta1-42 induced phenotypic changes in neurons that caused them to bind ...
journal_title：Neuropharmacology
pub_type： 杂志文章
doi：10.1016/j.neuropharm.2005.09.008
更新日期：2006-02-01 00:00:00
abstract：:1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP), or 0.9% saline, was administered to a group of common marmosets initially treated with the toxin 12-18 months previously. Initial treatment had consisted of a cumulative dose of 6-22 mg/kg (i.p.) which caused marked parkinsonism. Subsequently, the animals gradually ...
journal_title：Neuropharmacology
pub_type： 杂志文章
doi：10.1016/0028-3908(89)90122-6
更新日期：1989-10-01 00:00:00
abstract：:Bilateral injection of gamma-aminobutyric acid (GABA, 10-300 micrograms) into the substantia nigra (pars reticulata) of rats produced stereotyped sniffing and had an analgesic-like effect on the hot-plate but not on the tail-flick test. These effects of GABA (30 micrograms) were suppressed by simultaneous administrati...
journal_title：Neuropharmacology
pub_type： 杂志文章
doi：10.1016/0028-3908(88)90097-4
更新日期：1988-08-01 00:00:00
abstract：:The GABAA receptor/chloride ionophore (GABAR) is allosterically modulated by several classes of anticonvulsant agents, including benzodiazepines and barbiturates, and some alkyl-substituted butyrolactones. To test the hypothesis that the anticonvulsant butyrolactones act at a distinct positive-modulatory site on the G...
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：: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：:Aggression is a common symptom of several human psychiatric disorders. However, the drugs available to treat aggression are non-specific and can have unwanted side effects. The zebrafish is an ideal model for behavioural pharmacology. They are small, aggression can be measured reliably, and drugs can be applied by imm...
journal_title：Neuropharmacology
pub_type： 杂志文章,评审
doi：10.1016/j.neuropharm.2018.10.023
更新日期：2019-09-15 00:00:00
abstract：:The responses of the guinea-pig ileum myenteric plexus-longitudinal muscle to the food, drug and cosmetic dye erythrosin B (FD & C Red No. 3) were examined in acetylcholine- and electrically-stimulated preparations. Erythrosin B (10(-6)-10(-4)) reduced the amplitude of the mechanical responses produced by both stimuli...
journal_title：Neuropharmacology
pub_type： 杂志文章
doi：10.1016/0028-3908(83)90001-1
更新日期：1983-02-01 00:00:00
