Abstract:
:In this study we investigate the presence, modulation and biological function of P2 receptors and extracellular ATP in cultured cerebellar granule neurons. As we demonstrate by RT-PCR and western blotting, both P2X and P2Y receptor subtypes are expressed and furthermore regulated as a function of neuronal maturation. In early primary cultures, mRNA for most of the P2 receptor subtypes, except P2X(6), are found, while in older cultures only P2X(3), P2Y(1) and P2Y(6) mRNA persist. In contrast, P2 receptor proteins are more prominent in mature neurons, with the exception of P2Y(1). We also report that extracellular ATP acts as a cell death mediator for fully differentiated and mature granule neurons, for dissociated striatal primary cells and hippocampal organotypic cultures, inducing both apoptotic and necrotic features of degeneration. ATP causes cell death with EC(50) in the 20-50 microM range within few minutes of exposure and with a time lapse of at most two hours. Additional agonists for P2 receptors induce toxic effects, whereas selected antagonists are protective. Cellular swelling, lactic dehydrogenase release and nuclei fragmentation are among the features of ATP-evoked cell death, which also include direct P2 receptor modulation. Comparably to P2 receptor antagonists previously shown preventing glutamate-toxicity, here we report that competitive and non-competitive NMDA receptor antagonists inhibit the detrimental consequences of extracellular ATP. Due to the massive extracellular release of purine nucleotides and nucleosides often occurring during a toxic insult, our data indicate that extracellular ATP can now be included among the potential causes of CNS neurodegenerative events.
journal_name
Neuropharmacologyjournal_title
Neuropharmacologyauthors
Amadio S,D'Ambrosi N,Cavaliere F,Murra B,Sancesario G,Bernardi G,Burnstock G,Volonté Cdoi
10.1016/s0028-3908(01)00197-6subject
Has Abstractpub_date
2002-03-01 00:00:00pages
489-501issue
4eissn
0028-3908issn
1873-7064pii
S0028390801001976journal_volume
42pub_type
杂志文章abstract::Elimination of brain cholesterol occurs in the form of 24S-hydroxycholesterol (24S-HCh) that may modulate physiological processes outside the brain. Here, using microelectrode recording of postsynaptic responses (end-plate potentials, EPPs) and fluorescent marker (FM1-43) for endo-exocytosis we studied the effects of ...
journal_title:Neuropharmacology
pub_type: 杂志文章
doi:10.1016/j.neuropharm.2019.03.018
更新日期:2019-05-15 00:00:00
abstract::ɣ-aminobutyric-acid (GABA) functions as the principal inhibitory neurotransmitter in the central nervous system. Imbalances in GABAergic neurotransmission are involved in the pathophysiology of various neurological diseases such as epilepsy, Alzheimer's disease and stroke. GABA transporters (GATs) facilitate the termi...
journal_title:Neuropharmacology
pub_type: 杂志文章,评审
doi:10.1016/j.neuropharm.2019.05.021
更新日期:2019-12-15 00:00:00
abstract::To date, there are no interventions that impede the inexorable progression of Alzheimer's disease (AD), and currently-available drugs cholinesterase (AChE) inhibitors and the N-Methyl-d-Aspartate receptor antagonist, memantine, offer only modest symptomatic benefit. Moreover, a range of mechanistically-diverse agents ...
journal_title:Neuropharmacology
pub_type: 杂志文章,评审
doi:10.1016/j.neuropharm.2020.108099
更新日期:2020-10-15 00:00:00
abstract::Oxytocin (100 ng) injected unilaterally into the ventral subiculum of the hippocampus induces penile erection episodes, which started 30 min after treatment and were abolished by the prior injection of d(CH(2))(5)Tyr(Me)(2)-Orn(8)-vasotocin (2 μg), an oxytocin receptor antagonist, into the ventral subiculum. Oxytocin-...
journal_title:Neuropharmacology
pub_type: 杂志文章
doi:10.1016/j.neuropharm.2011.03.026
更新日期:2011-07-01 00:00:00
abstract::Orexin-A, -B play a crucial role in arousal and feeding by activating two G-protein-coupled receptors: orexin receptor 1 (OX1R) and orexin receptor 2 (OX2R). Orexins, along with orexin receptors, are expressed in retinal neurons, and they have been shown to differentially modulate excitatory AMPA receptors of amacrine...
journal_title:Neuropharmacology
pub_type: 杂志文章
doi:10.1016/j.neuropharm.2018.01.007
更新日期:2018-05-01 00:00:00
abstract::Compound IG20 is a newly synthesised sulphated glycolipid that promotes neuritic outgrowth and myelinisation, at the time it causes the inhibition of glial proliferation and facilitates exocytosis in chromaffin cells. Here we have shown that IG20 at 0.3-10 μM afforded neuroprotection in rat hippocampal slices stressed...
journal_title:Neuropharmacology
pub_type: 杂志文章
doi:10.1016/j.neuropharm.2016.12.016
更新日期:2017-04-01 00:00:00
abstract::To study the effects of maternal alcohol ingestion on brain adenylate cyclase in offspring, rats were given ethanol in the drinking water before, during and after gestation. Fifteen-day-old pups from alcoholic mothers had reduced body and wet brain weight and protein content with normal concentrations of DNA and RNA i...
journal_title:Neuropharmacology
pub_type: 杂志文章
doi:10.1016/0028-3908(83)90201-0
更新日期:1983-11-01 00:00:00
abstract::gamma-Aminobutyric acid (GABA, half-maximal inhibitory concentration, IC50 = 9.9 microM) and (-)-baclofen (IC50 = 4.5 microM) but not 10(-4) M muscimol, exerted a presynaptic inhibitory effect on cholinergic transmission in field-stimulated guinea-pig taenia coli preparations, in vitro. The antagonism by 10(-5) M (1S,...
journal_title:Neuropharmacology
pub_type: 杂志文章
doi:10.1016/0028-3908(87)90012-8
更新日期:1987-11-01 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...
journal_title:Neuropharmacology
pub_type: 杂志文章
doi:10.1016/0028-3908(94)00151-h
更新日期:1995-02-01 00:00:00
abstract::The alpha7 and alpha4beta2 nicotinic acetylcholine receptor (nAchR) subtypes have been shown to be involved in memory. It is also known that losses of frontal cortical nAchRs are correlated to declining memory function in Alzheimer's disease, but the subtype-specific role of frontal cortical nAchRs in memory has not b...
journal_title:Neuropharmacology
pub_type: 杂志文章
doi:10.1016/j.neuropharm.2007.03.008
更新日期:2007-06-01 00:00:00
abstract::Intrathecal (IT) injection of neostigmine (a cholinesterase inhibitor) has been reported to produce a significant anti-nociceptive effect in a number of inflammatory pain models. However, a potential anti-inflammatory effect of IT neostigmine in these models has not been investigated. In the present study, we have exa...
journal_title:Neuropharmacology
pub_type: 杂志文章
doi:10.1016/j.neuropharm.2004.12.024
更新日期:2005-09-01 00:00:00
abstract::Gastrin-releasing peptide (GRP) receptor-expressing (GRPR)+ neurons have a central role in the spinal transmission of itch. Because their fundamental regulatory mechanisms are not yet understood, it is important to determine how such neurons are excited and integrate itch sensation. In this study, we investigated the ...
journal_title:Neuropharmacology
pub_type: 杂志文章
doi:10.1016/j.neuropharm.2020.108025
更新日期:2020-06-15 00:00:00
abstract::Identification of synthetic agonists and antagonists at orphan receptors represents an important step for understanding their physiological function and therapeutic potential. Accordingly, we have recently described a non-peptide agonist at the opioid receptor like (ORL1) receptor (1S,3aS)-8-(2,3,3a,4,5,6-hexahydro-1H...
journal_title:Neuropharmacology
pub_type: 杂志文章
doi:10.1016/s0028-3908(01)00048-x
更新日期:2001-07-01 00:00:00
abstract::Exposure to abused drugs and stressful experience, two factors that promote the development of addiction, also modify synaptic function in the mesolimbic dopamine system. Here, we show that exposure to a novel environment produces functional synaptic adaptations in the nucleus accumbens (NAc) that mirror the effect of...
journal_title:Neuropharmacology
pub_type: 杂志文章
doi:10.1016/j.neuropharm.2011.01.038
更新日期:2011-12-01 00:00:00
abstract::The exact role of opioid receptor signaling in mediating voluntary wheel running is unclear. To provide additional understanding, female rats selectively bred for motivation of low (LVR) versus high voluntary running (HVR) behaviors were used. Aims of this study were 1) to identify intrinsic differences in nucleus acc...
journal_title:Neuropharmacology
pub_type: 杂志文章
doi:10.1016/j.neuropharm.2015.05.022
更新日期:2015-10-01 00:00:00
abstract::Presynaptic nicotinic acetylcholine receptors on striatal nerve terminals modulate the release of dopamine. Using rat striatal synaptosomes loaded with [3H]dopamine, we have characterized the action of the selective nicotinic agonist, (+/-)anatoxin-a, with respect to [3H]dopamine release, in order to explore the mecha...
journal_title:Neuropharmacology
pub_type: 杂志文章
doi:10.1016/0028-3908(95)00122-m
更新日期:1995-11-01 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::N-Ethyl-maleimide (NEM, 2.5 x 10(-5) M) inhibited the compound action potential of the phrenic nerve and increased the spontaneous release of transmitter from the nerve terminals, recorded as miniature endplate potentials. The first effect was the cause of a blockade of the phrenic nerve diaphragm preparation, during ...
journal_title:Neuropharmacology
pub_type: 杂志文章
doi:10.1016/0028-3908(89)90165-2
更新日期:1989-08-01 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
abstract::The serotonergic system is known to modulate and mediate many of the central nervous system effects of stress. Here we investigated the ability of serotonergic agents to reverse the inhibition of the induction of hippocampal long-term potentiation (LTP) caused by prior exposure to inescapable stress. Elevated platform...
journal_title:Neuropharmacology
pub_type: 杂志文章
doi:10.1016/j.neuropharm.2008.05.006
更新日期:2008-08-01 00:00:00
abstract::Under conditions in which NG-nitro-L-arginine (NOArg) treatment prevents morphine tolerance, NOArg induces a slow progressive inhibition of nitric oxide synthase (NOS), starting at approx. 20% after a single treatment and increasing to approx. 65% after 10 days. Studies designed to examine potential changes in NOS lev...
journal_title:Neuropharmacology
pub_type: 杂志文章
doi:10.1016/0028-3908(94)90050-7
更新日期:1994-11-01 00:00:00
abstract::The loci coeruleus of freely moving cats were perfused bilaterally with acetylcholine at a dose of 0.001 microgram/microliter per min, while the animals were recorded polygraphically. The controls consisted of experiments in which no perfusions were done, and experiments in which the loci coeruleus were perfused bilat...
journal_title:Neuropharmacology
pub_type: 杂志文章
doi:10.1016/0028-3908(82)90174-5
更新日期:1982-11-01 00:00:00
abstract::Potentiation of the 5-HT3 receptor-mediated ion current in mouse N1E-115 neuroblastoma cells by 5-hydroxyindole (5-OHi) and three analogues (5-aminoindole, catechol and indole) was examined using whole-cell voltage clamp and single channel patch clamp techniques. The substances tested enhanced the amplitude of the max...
journal_title:Neuropharmacology
pub_type: 杂志文章
doi:10.1016/s0028-3908(97)00045-2
更新日期:1997-04-01 00:00:00
abstract::The aim of this study was to investigate the pharmacological characteristics of the 5-hydroxytryptamine-(5-HT)-induced electrical response in cultured neuroblastoma N1E-115 cells of the mouse. In these cells 5-HT induces a transient membrane depolarization, which is associated with a transient inward current, that has...
journal_title:Neuropharmacology
pub_type: 杂志文章
doi:10.1016/0028-3908(88)90048-2
更新日期:1988-03-01 00:00:00
abstract::Groups of hypophysectomised rats were given either an electroconvulsive shock (ECS; 125V, 1 sec) once daily for 10 days or a sham-shock. Twenty-four hours after the final treatment both groups were tested for their responses to the dopamine agonist, apomorphine, the 5-hydroxytryptamine agonist, quipazine, and the alph...
journal_title:Neuropharmacology
pub_type: 杂志文章
doi:10.1016/0028-3908(82)90079-x
更新日期:1982-09-01 00:00:00
abstract::The lateral habenula (LHb) is critical for modulation of negative reinforcement, punishment and aversive responses. In light of the success of deep-brain-stimulation (DBS) in the treatment of neurological disorders, we explored the use of LHb DBS as a method of intervention in cocaine self-administration, extinction, ...
journal_title:Neuropharmacology
pub_type: 杂志文章
doi:10.1016/j.neuropharm.2010.06.008
更新日期:2010-11-01 00:00:00
abstract::Recent studies indicated that epigenetic modification, especially DNA methylation, play an important role in the persistence of addiction-related memory. 5-aza-2-deoxycytidine (5-aza), an inhibitor of DNA methyltransferases, was approved for clinical treatment. However, it is not clear whether 5-aza is involved in opi...
journal_title:Neuropharmacology
pub_type: 杂志文章
doi:10.1016/j.neuropharm.2014.08.005
更新日期:2014-11-01 00:00:00
abstract::Granule cell axon terminals of rat cerebellum possess benzodiazepine-insensitive GABA(A) receptors mediating glutamate release. We have investigated the ability of benzodiazepines, ethanol and furosemide to modulate the function of these receptors in the cerebellum of alcohol-tolerant (AT) and alcohol-nontolerant (ANT...
journal_title:Neuropharmacology
pub_type: 杂志文章
doi:10.1016/s0028-3908(99)00025-8
更新日期:1999-09-01 00:00:00
abstract::Nitronyl nitroxides (NN) effectively decompose free radicals (. As brain endothelium, forming the blood-brain barrier (BBB), is both the main source and the target of reactive species during cerebral oxidative stress, we studied the effect of NN on brain endothelial cells injured by the mediator of oxidative stress H(...
journal_title:Neuropharmacology
pub_type: 杂志文章
doi:10.1016/s0028-3908(02)00180-6
更新日期:2002-11-01 00:00:00
abstract::Maternal aggression is highly expressed during lactation and serves to protect the developing young from intruders that may injure the offspring. One neurochemical modulator of maternal aggression appears to be arginine vasopressin (AVP). Earlier research supports a role for AVP in maternal aggression in rats as treat...
journal_title:Neuropharmacology
pub_type: 杂志文章
doi:10.1016/j.neuropharm.2009.06.032
更新日期:2010-01-01 00:00:00