Abstract：
:The overexpression of Kir3.2, a subunit of the G protein-gated inwardly rectifying K(+) channel, is implicated in some of the neurological phenotypes of Down syndrome (DS). Chemical compounds that block Kir3.2 are expected to improve the symptoms of DS. The purpose of this study is to develop a cell-based screening system to identify Kir3.2 blockers and then investigate the mode of action of the blocker. Chemical screening was carried out using a K(+) transporter-deficient yeast strain that expressed a constitutively active Kir3.2 mutant. The mode of action of an effective blocker was electrophysiologically analyzed using Kir channels expressed in Xenopus oocytes. Proflavine was identified to inhibit the growth of Kir3.2-transformant cells and Kir3.2 activity in a concentration-dependent manner. The current inhibition was strong when membrane potentials (Vm) was above equilibrium potential of K(+) (EK). When Vm was below EK, the blockage apparently depended on the difference between Vm and [K(+)]. Furthermore, the inhibition became stronger by lowering extracellular [K(+)]. These results indicated that the yeast strain serves as a screening system to isolate Kir3.2 blockers and proflavine is a prototype of a pore blocker of Kir3.2.
journal_name
Neuropharmacologyjournal_title
Neuropharmacologyauthors
Kawada H,Inanobe A,Kurachi Ydoi
10.1016/j.neuropharm.2016.05.016subject
Has Abstractpub_date
2016-10-01 00:00:00pages
18-28eissn
0028-3908issn
1873-7064pii
S0028-3908(16)30214-3journal_volume
109pub_type
杂志文章abstract：:Agonists and antagonists of gamma-aminobutyric acid, i.e. GABAergic drugs, such as muscimol, baclofen or bicuculline, alone or in combination, exhibited analgesic effects per se and enhanced the analgesia induced by morphine. The analgesic effects of GABAergic drugs were unaffected by administration of naloxone in a d...
journal_title：Neuropharmacology
pub_type： 杂志文章
doi：10.1016/0028-3908(83)90101-6
更新日期：1983-06-01 00:00:00
abstract：:Withdrawal from chronic ethanol intoxication is associated with a reduction of dopamine neurotransmission. However, the mechanisms of dopamine depletion, a putative neurochemical correlate of the dysphoric symptomatology, are not yet understood. To assess the role of L-type calcium channels in the inhibition of the do...
journal_title：Neuropharmacology
pub_type： 杂志文章
doi：10.1016/s0028-3908(99)00039-8
更新日期：1999-09-01 00:00:00
abstract：:The bed nucleus of the stria terminalis was first described nearly a century ago and has since emerged as a region central to motivated behavior and affective states. The last several decades have firmly established a role for the BNST in drug-associated behavior and implicated this region in addiction-related process...
journal_title：Neuropharmacology
pub_type： 杂志文章,评审
doi：10.1016/j.neuropharm.2017.03.028
更新日期：2017-08-01 00:00:00
abstract：:Phosphodiesterases (PDE) are the only enzymes that degrade cAMP and cGMP which are second messengers crucial to memory consolidation. Different PDE inhibitors have been developed and tested for their memory-enhancing potential, but the occurrence of side effects has hampered clinical progression. As separate inhibitio...
journal_title：Neuropharmacology
pub_type： 杂志文章
doi：10.1016/j.neuropharm.2020.108414
更新日期：2021-02-15 00:00:00
abstract：:Clinical studies have shown that the major psychoactive ingredient of Cannabis sativa Δ9-tetrahydrocannabinol (THC) has some analgesic efficacy in neuropathic pain states. However, THC has a significant side effect profile. We examined whether the profile of THC could be improved by co-administering it with the first-...
journal_title：Neuropharmacology
pub_type： 杂志文章
doi：10.1016/j.neuropharm.2018.10.006
更新日期：2019-01-01 00:00:00
abstract：:Palatability driven feeding and voluntary physical activity are mediated by and influence similar neural mechanisms, notably through the actions of opioids within the nucleus accumbens. Recent studies suggest that access to a voluntary running wheel results in sex dependent behavioral and physiological adaptations rel...
journal_title：Neuropharmacology
pub_type： 杂志文章
doi：10.1016/j.neuropharm.2019.05.017
更新日期：2019-09-01 00:00:00
abstract：:The endocannabinoid system (ECS) comprises the cannabinoid receptors CB1 and CB2 and their endogenous arachidonic acid-derived agonists 2-arachidonoyl glycerol and anandamide, which play important neuromodulatory roles. Recently, a novel class of negative allosteric CB1 receptor peptide ligands, hemopressin-like pepti...
journal_title：Neuropharmacology
pub_type： 杂志文章
doi：10.1016/j.neuropharm.2015.03.021
更新日期：2015-11-01 00:00:00
abstract：:Fluorescence based probes provide a novel way to study the dynamic internalization process of G protein-coupled receptors (GPCRs). Recent advances in the rational design of fluorescent ligands for GPCRs have been used here to generate new fluorescent agonists containing tripeptide linkers for the adenosine A3 receptor...
journal_title：Neuropharmacology
pub_type： 杂志文章
doi：10.1016/j.neuropharm.2015.04.013
更新日期：2015-11-01 00:00:00
abstract：:The dopaminergic receptors of planaria have been studied with pharmacological and biochemical criteria. Dopamine D1 selective agonists (CY 208243 (10 micrograms/ml) and SKF 38393 (10 micrograms/ml] induced in planaria typical screw-like hyperkinesias, that were inhibited by a D1 antagonist (SCH 23390 (10 micrograms/ml...
journal_title：Neuropharmacology
pub_type： 杂志文章
doi：10.1016/0028-3908(89)90013-0
更新日期：1989-12-01 00:00:00
abstract：:Recently, the presence of two high affinity binding sites for phencyclidine were described in guinea pig brain, with one site coupled to the glutamate excitatory amino acid receptor, specifically activated by N-methyl-D-aspartate (NMDA) (site 1) and the other site associated with the dopamine (DA) reuptake carrier (si...
journal_title：Neuropharmacology
pub_type： 杂志文章
doi：10.1016/0028-3908(90)90154-j
更新日期：1990-09-01 00:00:00
abstract：:2-[p-(2-carboxyethyl)-phenylethylamino]-5'-N-ethylcarboxamidoadeno sine (CGS 21680) is considered a selective ligand for adenosine A2A receptors, which are known to be enriched in striatum and olfactory tubercle. We have investigated the characteristics of [3H]CGS 21680 binding in several brain regions using quantitat...
journal_title：Neuropharmacology
pub_type： 杂志文章
doi：10.1016/0028-3908(95)00009-u
更新日期：1995-04-01 00:00:00
abstract：:An infusion of dopamine for 13 days into the nucleus accumbens of rat caused biphasic peaks of hyperactivity responding during infusion and an enhanced locomotor responsiveness to the dopamine agonist (-)N-n-propylnorapomorphine [(-)NPA] after the infusion when rats where initially preselected as low activity responde...
journal_title：Neuropharmacology
pub_type： 杂志文章
doi：10.1016/0028-3908(85)90073-5
更新日期：1985-03-01 00:00:00
abstract：:Radioligand binding studies were performed in membranes of human cerebellum using [125I][Tyr3]octreotide also known as [125I]204-090, [125I]LTT-SRIF-28 ([Leu8, D-Trp22, 125I-Tyr25]SRIF-28) and [125I]CGP 23996 ([125I]c[Asu-Lys-Asn-Phe-Trp-Lys-Thr-Tyr-Thr-Ser]) to characterize the nature of cerebellar somatostatin recep...
journal_title：Neuropharmacology
pub_type： 杂志文章
doi：10.1016/0028-3908(96)84643-0
更新日期：1996-06-01 00:00:00
abstract：:The effects of the dopamine antagonists haloperidol and sultopride were investigated on the twitch response, evoked by 0.1 Hz stimulation of guinea-pig isolated ileal longitudinal muscle, and on the inhibition of the twitch response induced by 10 Hz stimulation (post-tetanic twitch inhibition) and by application of op...
journal_title：Neuropharmacology
pub_type： 杂志文章
doi：10.1016/0028-3908(94)00166-p
更新日期：1995-05-01 00:00:00
abstract：:We investigated block of voltage-dependent Ca channels in freshly dissociated rat central and peripheral neurons by the synthetic peptide omega-Aga-IVA. Synthetic omega-Aga-IVA blocked approximately 90% of the high-threshold Ca current in cerebellar Purkinje neurons with an estimated Kd of approximately 1.5 nM, slight...
journal_title：Neuropharmacology
pub_type： 杂志文章
doi：10.1016/0028-3908(93)90010-z
更新日期：1993-11-01 00:00:00
abstract：:Vortioxetine is a multimodal drug that blocks serotonin (5-HT) reuptake and directly modulates 5-HT receptors. The effects of subacute and long-term administration of vortioxetine on various aspects of catecholamine and glutamate systems were investigated using single-unit extracellular recordings and microiontophores...
journal_title：Neuropharmacology
pub_type： 杂志文章
doi：10.1016/j.neuropharm.2017.10.036
更新日期：2018-01-01 00:00:00
abstract：:Cyclic nucleotide-gated (CNG) channels, which are directly activated by cAMP and cGMP, have long been known to play a key role in retinal and olfactory signal transduction. Emerging evidence indicates that CNG channels are also involved in signaling pathways important for pain processing. Here, we found that the expre...
journal_title：Neuropharmacology
pub_type： 杂志文章
doi：10.1016/j.neuropharm.2020.108087
更新日期：2020-07-01 00:00:00
abstract：:Up to 80% of cancer patients are affected by the cancer anorexia-cachexia syndrome (CACS), which leads to excessive body weight loss, reduced treatment success and increased lethality. The area postrema/nucleus of the solitary tract (AP/NTS) region emerged as a central nervous key structure in this multi-factorial pro...
journal_title：Neuropharmacology
pub_type： 杂志文章
doi：10.1016/j.neuropharm.2020.108289
更新日期：2020-12-01 00:00:00
abstract：:The effects of several stress procedures on the release of 5-HT in the dorsal and median raphe nuclei (DRN and MRN, respectively) and in forebrain structures of the rat brain innervated by both nuclei have been studied using intracerebral microdialysis. Handling for 30 sec, a saline injection and forced swimming for 5...
journal_title：Neuropharmacology
pub_type： 杂志文章
doi：10.1016/s0028-3908(97)00048-8
更新日期：1997-04-01 00:00:00
abstract：:The secreted glycoprotein Dickkopf-1 (Dkk1), an antagonist of the Wnt/β-catenin pathway, has been implicated in many neurodegenerative diseases. However, it is unknown whether Dkk1 is involved in the pathogenesis of Parkinson's disease (PD). In this study, we discovered that Dkk1 was induced in MPP(+)-treated PC12 cel...
journal_title：Neuropharmacology
pub_type： 杂志文章
doi：10.1016/j.neuropharm.2012.10.031
更新日期：2013-04-01 00:00:00
abstract：:The effects of haloperidol, chlorpromazine and clozapine on transmitter release have been studied by measuring the simultaneous release of dopamine and acetylcholine from tissue slices of nucleus accumbens and striatum in vitro following in vivo drug application, either a single dose or daily for periods of up to 25 d...
journal_title：Neuropharmacology
pub_type： 杂志文章
doi：10.1016/0028-3908(82)90043-0
更新日期：1982-06-01 00:00:00
abstract：:The effects of the putative, selective dopamine autoreceptor antagonist (+)-AJ 76 on yawning, penile grooming and mouth movements induced by small doses of apomorphine in male rats were examined. Yawning induced by 0.05mg/kg apomorphine was dose dependently blocked by (+)-AJ-76, significant decreases being observed at...
journal_title：Neuropharmacology
pub_type： 杂志文章
doi：10.1016/0028-3908(89)90021-x
更新日期：1989-12-01 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：:We have used a focal stimulation method to study neurotransmission at synapses onto hippocampal pyramidal neurons in cultures derived from neonatal rats. Single functional boutons were visualized by activity-dependent preloading with the fluorescent dye FM1-43, then focally stimulated by localized application of eleva...
journal_title：Neuropharmacology
pub_type： 杂志文章
doi：10.1016/0028-3908(95)00143-t
更新日期：1995-11-01 00:00:00
abstract：:The influence of naloxone (a narcotic antagonist), bicuculline (a GABA antagonist), phentolamine (an alpha-blocking agent), propranolol (a beta-adrenergic blocking agent), haloperidol (a dopaminergic blocking agent), methysergide (a serotonergic blocking agent) and atropine (a muscarinic blocking agent), on the antino...
journal_title：Neuropharmacology
pub_type： 杂志文章
doi：10.1016/0028-3908(84)90143-6
更新日期：1984-06-01 00:00:00
abstract：:Deficits in social memory, cognition, and aberrant responses to stimulants are common among persons affected by schizophrenia and other conditions with a presumed developmental etiology. We previously found that expression changes in the adenosine metabolizing enzyme adenosine kinase (ADK) in the adult brain are assoc...
journal_title：Neuropharmacology
pub_type： 杂志文章
doi：10.1016/j.neuropharm.2018.08.025
更新日期：2018-10-01 00:00:00
abstract：:Excessive glutamate-mediated synaptic transmission and secondary excitotoxicity have been proposed as key determinants of neurodegeneration in many neurological diseases. Soluble mediators of inflammation have recently gained attention owing to their ability to enhance glutamate transmission and affect synaptic sensit...
journal_title：Neuropharmacology
pub_type： 杂志文章,评审
doi：10.1016/j.neuropharm.2014.09.022
更新日期：2015-09-01 00:00:00
abstract：:The 15q25 gene cluster contains genes that code for the α5, α3, and β4 nicotinic acetylcholine receptor (nAChRs) subunits, and in human genetic studies, has shown the most robust association with smoking behavior and nicotine dependence to date. The limited available animal studies implicate a role for the α5 and β4 n...
journal_title：Neuropharmacology
pub_type： 杂志文章
doi：10.1016/j.neuropharm.2013.01.017
更新日期：2013-07-01 00:00:00
abstract：:A subgroup of anticonvulsant and neuroleptic drugs acts through the potentiation of GABA pathways. The regulatory role of GABA in neuronal circuit formation is related to its depolarizing action that supports activity-dependent synaptogenesis. We hypothesized that elevated levels of GABA in the immature brain modify s...
journal_title：Neuropharmacology
pub_type： 杂志文章
doi：10.1016/j.neuropharm.2013.12.015
更新日期：2014-04-01 00:00:00
abstract：:Efflux of exogenous [3H]taurine from superfused slices of cerebral cortex of rat was enhanced by the calcium chelators EDTA and EGTA and by large concentrations of unlabelled taurine and histidine. The enhancement by EDTA and EGTA could be totally blocked by excess calcium, but that by the amino acids only partially. ...
journal_title：Neuropharmacology
pub_type： 杂志文章
doi：10.1016/0028-3908(84)90202-8
更新日期：1984-03-01 00:00:00
