Allosteric modulation of GluN2C/GluN2D-containing NMDA receptors bidirectionally modulates dopamine release: implication for Parkinson's disease.


BACKGROUND AND PURPOSE:Allosteric modulators of ionotropic receptors and GPCRs might constitute valuable therapeutic tools for intervention in several diseases, including Parkinson's disease (PD). However, the possibility that some of these compounds could alter neurotransmission in health and disease has not been thoroughly examined. Hence, we determined whether CIQ, a positive allosteric modulator of NMDA receptors that contain the GluN2C or GluN2D subunits, modulates dopamine release in the striatum of control mice and of a mouse model of presymptomatic Parkinsonism. EXPERIMENTAL APPROACH:We used amperometry to measure, in mouse brain slices containing the dorsal striatum, dopamine release evoked by stimulations that mimicked tonic (single pulses) or phasic (trains) activity. We used control mice and mice with a partial, 6-hydroxydopamine-induced, degeneration of dopaminergic neurons in the substantia nigra. KEY RESULTS:In control mice, CIQ inhibited tonic dopamine release and induced an initial inhibition followed by a long-lasting increase in phasic release. Pirenzepine, a muscarinic receptor antagonist, blocked the depression of release induced by CIQ, but not the long-lasting potentiation. CIQ also increased action potential firing in striatal cholinergic interneurons. In the partially dopamine-depleted striatum, CIQ induced an inhibition followed by a potentiation of both tonic and phasic release, but did not significantly increase the firing of cholinergic interneurons. CONCLUSIONS AND IMPLICATIONS:CIQ has bidirectional, activity- and ACh-dependent, modulatory effects on dopamine release in the striatum. This study suggests a potentially valuable means to enhance dopamine release in presymptomatic Parkinsonism.


Br J Pharmacol


Zhang X,Feng ZJ,Chergui K




Has Abstract


2014-08-01 00:00:00












  • Physiological antagonism between ventricular beta 1-adrenoceptors and alpha 1-adrenoceptors but no evidence for beta 2- and beta 3-adrenoceptor function in murine heart.

    abstract::1. Murine left atrium lacks inotropic beta(2)-adrenoceptor function. We investigated whether beta(2)-adrenoceptors are involved in the cardiostimulant effects of (-)-adrenaline on spontaneously beating right atria and paced right ventricular myocardium of C57BL6 mice. We also studied a negative inotropic effect of (-)...

    journal_title:British journal of pharmacology

    pub_type: 杂志文章


    authors: Heubach JF,Rau T,Eschenhagen T,Ravens U,Kaumann AJ

    更新日期:2002-05-01 00:00:00

  • Protease-activated receptor 1 inhibition protects mice against thrombin-dependent respiratory syncytial virus and human metapneumovirus infections.

    abstract:BACKGROUND AND PURPOSE:Protease-activated receptor 1 (PAR1) has been demonstrated to be involved in the pathogenesis of viral diseases. However, its role remains controversial. The goal of our study was to investigate the contribution of PAR1 to respiratory syncytial virus (RSV) and human metapneumovirus (hMPV) infecti...

    journal_title:British journal of pharmacology

    pub_type: 杂志文章


    authors: Lê VB,Riteau B,Alessi MC,Couture C,Jandrot-Perrus M,Rhéaume C,Hamelin MÈ,Boivin G

    更新日期:2018-01-01 00:00:00

  • The control of the contraction of myocytes from guinea-pig heart by the resting membrane potential.

    abstract::1. The influence of different holding potentials (-120 to -70 mV) on the contraction of enzymatically dispersed myocytes from guinea-pig hearts was evaluated. Contractions were elicited by repetitive depolarizations to 0 mV at 0.5 Hz. 2. While ineffective at 140 and 5 mmol l-1 [Na+]o and pipette Na+, respectively, dep...

    journal_title:British journal of pharmacology

    pub_type: 杂志文章


    authors: Mermi J,Yajima M,Ebner F

    更新日期:1991-11-01 00:00:00

  • Preclinical evaluation of [18 F]MA3: a CB2 receptor agonist radiotracer for PET.

    abstract:BACKGROUND AND PURPOSE:Non-invasive in vivo imaging of cannabinoid CB2 receptors using PET is pursued to study neuroinflammation. The purpose of this study is to evaluate the in vivo binding specificity of [18 F]MA3, a CB2 receptor agonist, in a rat model with local overexpression of human (h) CB2 receptors. METHODS:[...

    journal_title:British journal of pharmacology

    pub_type: 杂志文章


    authors: Attili B,Celen S,Ahamed M,Koole M,Haute CVD,Vanduffel W,Bormans G

    更新日期:2019-05-01 00:00:00

  • Modulation of visceral pain and inflammation by protease-activated receptors.

    abstract::The gastrointestinal (GI) tract is exposed to a large array of proteases, under both physiological and pathophysiological conditions. The discovery of G protein-coupled receptors activated by proteases, the protease-activated receptors (PARs), has highlighted new signaling functions for proteases in the GI tract, part...

    journal_title:British journal of pharmacology

    pub_type: 杂志文章,评审


    authors: Vergnolle N

    更新日期:2004-04-01 00:00:00

  • An examination of 5-hydroxytryptamine receptors in human saphenous vein.

    abstract::We have examined the effects of antagonists on the isometric contraction of the human saphenous vein produced by 5-hydroxytryptamine (5-HT). The 5-HT2-antagonist ketanserin (1 microM) had little effect on the lower part of the concentration-response curve to 5-HT, but markedly shifted the upper part of the curve. Yohi...

    journal_title:British journal of pharmacology

    pub_type: 杂志文章


    authors: Docherty JR,Hyland L

    更新日期:1986-09-01 00:00:00

  • Oestradiol-induced relaxation of rabbit basilar artery by inhibition of voltage-dependent Ca channels through GTP-binding protein.

    abstract::1. Effects of oestradiol on the electrical and mechanical properties of the rabbit basilar artery were investigated by use of microelectrode, patch-clamp and isometric tension recording methods. 2. Oestradiol (10 nM-100 microM) relaxed arterial tissue pre-contracted by excess [K]o solution (30 mM) in a concentration-d...

    journal_title:British journal of pharmacology

    pub_type: 杂志文章


    authors: Ogata R,Inoue Y,Nakano H,Ito Y,Kitamura K

    更新日期:1996-01-01 00:00:00

  • Pharmacological and certain chemical properties of AH 10407, an unusually short-acting, competitive neuromuscular blocking drug, and some related compounds.

    abstract::1,1-Azobis[3-methyl-2-phenylbenzimidazolinium]dimethanesulphonate (AH 10407) has an ultrashort, competitive neuromuscular blocking action in the mouse, cat, dog, Cynamolgus monkey and cotton-eared marmoset. 2 AH 10407 is chemically unstable in bicarbonate-containing solutions and is degraded to inactive products. The ...

    journal_title:British journal of pharmacology

    pub_type: 杂志文章


    authors: Brittain RT,Jack D,Tyers MB

    更新日期:1977-09-01 00:00:00

  • The ABCG family of membrane-associated transporters: you don't have to be big to be mighty.

    abstract::Along with many other mammalian ATP-binding cassette (ABC) transporters, members of the ABCG group are involved in the regulated transport of hydrophobic compounds across cellular membranes. In humans, five ABCG family members have been identified, encoding proteins ranging from 638 to 678 amino acids in length. All f...

    journal_title:British journal of pharmacology

    pub_type: 杂志文章,评审


    authors: Kerr ID,Haider AJ,Gelissen IC

    更新日期:2011-12-01 00:00:00

  • The role of histamine receptors in the release of renin.

    abstract::1 The effect of intrarenal histamine, dimaprit (H2-agonist) and 2-(2-pyridyl) ethylamine (H1-agonist) on renin release was examined in anaesthetized dogs. 2 In dogs with intact kidneys, histamine and dimaprit administration resulted in renal vasodilatation, a two fold increase in urinary sodium excretion, and no chang...

    journal_title:British journal of pharmacology

    pub_type: 杂志文章


    authors: Gerber JG,Nies AS

    更新日期:1983-05-01 00:00:00

  • Response of the rat ileum, uterus and vas deferens to carbachol and acetylcholine following repeated daily administration of a cholinesterase inhibitor.

    abstract::1. Daily i.p. administration, for eight days, of the cholinesterase inhibitor disulfoton to rats produced mild to moderate signs of intoxication (tremors, incontinence and diarrhoea) but no deaths.2. Segments of ileum taken from the treated rats were subsensitive to carbachol but the vas deferens and the uterus did no...

    journal_title:British journal of pharmacology

    pub_type: 杂志文章


    authors: Foley DJ,McPhillips JJ

    更新日期:1973-07-01 00:00:00

  • Role of oxidative stress and nitric oxide in regulation of spontaneous tone in aorta of DOCA-salt hypertensive rats.

    abstract::1. The roles of nitric oxide (NO), superoxide anion (O(2)(-)), and hydrogen peroxide (H(2)O(2)) in the modulation of spontaneous tone were investigated in isolated aorta from deoxycorticosterone acetate (DOCA)-salt hypertensive rats. 2. Increases in preload from 1 to 5 g were accompanied by increases in spontaneous to...

    journal_title:British journal of pharmacology

    pub_type: 杂志文章


    authors: Ghosh M,Wang HD,McNeill JR

    更新日期:2004-02-01 00:00:00

  • The calcium ionophore A23187 induces endothelium-dependent contractions in femoral arteries from rats with streptozotocin-induced diabetes.

    abstract:BACKGROUND AND PURPOSE:To study the importance of endothelium-derived contracting factors (EDCFs) in arteries of rats with type I diabetes. EXPERIMENTAL APPROACH:Rat femoral arteries were collected four or twelve weeks after induction of diabetes with streptozotocin. Rings, with or without endothelium, were suspended ...

    journal_title:British journal of pharmacology

    pub_type: 杂志文章


    authors: Shi Y,Feletou M,Ku DD,Man RY,Vanhoutte PM

    更新日期:2007-03-01 00:00:00

  • The compound BTB06584 is an IF1 -dependent selective inhibitor of the mitochondrial F1 Fo-ATPase.

    abstract:BACKGROUND AND PURPOSE:Ischaemia compromises mitochondrial respiration. Consequently, the mitochondrial F1 Fo-ATPsynthase reverses and acts as a proton-pumping ATPase, so maintaining the mitochondrial membrane potential (ΔΨm ), while accelerating ATP depletion and cell death. Here we have looked for a molecule that can...

    journal_title:British journal of pharmacology

    pub_type: 杂志文章


    authors: Ivanes F,Faccenda D,Gatliff J,Ahmed AA,Cocco S,Cheng CH,Allan E,Russell C,Duchen MR,Campanella M

    更新日期:2014-09-01 00:00:00

  • Effect of salmeterol on human nasal epithelial cell ciliary beating: inhibition of the ciliotoxin, pyocyanin.

    abstract::1. Patients with airway infection by Pseudomonas aeruginosa have impaired mucociliary clearance. Pyocyanin is a phenazine pigment produced by P. aeruginosa which is present in the sputum of colonized patients, slows human ciliary beat frequency (CBF) in vitro and slows mucociliary transport in vivo in the guinea-pig. ...

    journal_title:British journal of pharmacology

    pub_type: 杂志文章


    authors: Kanthakumar K,Cundell DR,Johnson M,Wills PJ,Taylor GW,Cole PJ,Wilson R

    更新日期:1994-06-01 00:00:00

  • The partial purification and bioassay of a toxin present in extracts of the sea anemone, Tealia felina (L.).

    abstract::1. Column chromatography with Agarose A50m followed by Sephadex G100 was used to separate a fraction (extract II) in the molecular weight range 12,000 to 14,000 daltons from saline extracts of the sea anemone, Tealia felina. 2. Extract II inhibited histamine-induced contractions of the guinea-pig ileum and produced ha...

    journal_title:British journal of pharmacology

    pub_type: 杂志文章


    authors: Aldeen SI,Elliott RC,Sheardown M

    更新日期:1981-02-01 00:00:00

  • Hepatocyte growth factor regulates human trophoblast motility and invasion: a role for nitric oxide.

    abstract::1. The expression of hepatocyte growth factor (HGF) is essential for normal placental development although its function is unknown. In this study we examined the effect of HGF on trophoblast cell motility and invasion of fibrin gels and investigated the possible role of nitric oxide (NO) in this process. 2. The human ...

    journal_title:British journal of pharmacology

    pub_type: 杂志文章


    authors: Cartwright JE,Holden DP,Whitley GS

    更新日期:1999-09-01 00:00:00

  • Effects of endothelin receptor antagonism with bosentan on peripheral nerve function in experimental diabetes.

    abstract::1. The effects of the non-selective endothelin (ET) receptor (ETA/ETB) antagonist, bosentan, on sciatic nerve dysfunction in experimental diabetes were investigated. 2. Rats with 5-6 weeks untreated streptozotocin-diabetes exhibited characteristic slowed motor nerve conduction velocity (mean +/- s.d., 36.6 +/- 3.4 m s...

    journal_title:British journal of pharmacology

    pub_type: 杂志文章


    authors: Stevens EJ,Tomlinson DR

    更新日期:1995-05-01 00:00:00

  • Modulation by prednisolone of calcium handling in skeletal muscle cells.

    abstract::1. Increased calcium (Ca2+) influx has been incriminated as a potential pathological mechanism in the chronic skeletal muscle degeneration exhibited by Duchenne muscular dystrophy (DMD) patients. We have studied the influence of the glucocorticoid alpha-methylprednisolone (PDN), the only drug known to have a beneficia...

    journal_title:British journal of pharmacology

    pub_type: 杂志文章


    authors: Metzinger L,Passaquin AC,Leijendekker WJ,Poindron P,Rüegg UT

    更新日期:1995-12-01 00:00:00

  • Cannabinoids inhibit cholinergic contraction in human airways through prejunctional CB1 receptors.

    abstract:BACKGROUND AND PURPOSE:Marijuana smoking is widespread in many countries, and the use of smoked synthetic cannabinoids is increasing. Smoking a marijuana joint leads to bronchodilation in both healthy subjects and asthmatics. The effects of Δ(9) -tetrahydrocannabinol and synthetic cannabinoids on human bronchus reactiv...

    journal_title:British journal of pharmacology

    pub_type: 杂志文章


    authors: Grassin-Delyle S,Naline E,Buenestado A,Faisy C,Alvarez JC,Salvator H,Abrial C,Advenier C,Zemoura L,Devillier P

    更新日期:2014-06-01 00:00:00

  • The influence of psychotropic drugs on aldole, mitochondrial malic dehydrogenase and Mg++na+K+ adenosine triphosphatase.

    abstract::1. The experiment investigated the effects of psychotropic drugs on enzymes in vitro.2. Chlorpromazine inhibits mitochondrial malate dehydrogenase in concentrations of 1.4x10(-4)M and above. No effect was observed below this concentration.3. A sharp inflection in the [unk]/drug plot was also seen with chlorpromazine (...

    journal_title:British journal of pharmacology

    pub_type: 杂志文章


    authors: Chowdhury AK,Rogers H,Skinner A,Spector RG,Watts DC

    更新日期:1969-10-01 00:00:00

  • Human alpha-calcitonin gene-related peptide stimulates adenylate cyclase and guanylate cyclase and relaxes rat thoracic aorta by releasing nitric oxide.

    abstract::1. The signal transduction pathway for vasorelaxation induced by human alpha-calcitonin gene-related peptide (human alpha-CGRP) was studied in rat thoracic aortic rings preconstricted with noradrenaline (10(-7) M). 2. Vasorelaxation by human alpha-CGRP was inhibited by haemoglobin (10(-6) M) and methylene blue (10(-5)...

    journal_title:British journal of pharmacology

    pub_type: 杂志文章


    authors: Gray DW,Marshall I

    更新日期:1992-11-01 00:00:00

  • Characterization of a rat model of bortezomib-induced painful neuropathy.

    abstract:BACKGROUND AND PURPOSE:Bortezomib (Velcade®) is a breakthrough treatment for multiple myeloma, significantly improving patient survival. However, its use is limited by painful neuropathy often resulting in dose reduction/cessation of first-line treatment due to lack of treatment. The aim of this study was to characteri...

    journal_title:British journal of pharmacology

    pub_type: 杂志文章


    authors: Duggett NA,Flatters SJL

    更新日期:2017-12-01 00:00:00

  • Allosteric and orthosteric pharmacology of cannabidiol and cannabidiol-dimethylheptyl at the type 1 and type 2 cannabinoid receptors.

    abstract:BACKGROUND AND PURPOSE:We sought to understand why (-)-cannabidiol (CBD) and (-)-cannabidiol-dimethylheptyl (CBD-DMH) exhibit distinct pharmacology, despite near identical structures. EXPERIMENTAL APPROACH:HEK293A cells expressing either human type 1 cannabinoid (CB1 ) receptors or CB2 receptors were treated with CBD ...

    journal_title:British journal of pharmacology

    pub_type: 杂志文章


    authors: Tham M,Yilmaz O,Alaverdashvili M,Kelly MEM,Denovan-Wright EM,Laprairie RB

    更新日期:2019-05-01 00:00:00

  • Extracellular ATP and UTP activation of phospholipase D is mediated by protein kinase C-epsilon in rat renal mesangial cells.

    abstract::1. We have studied whether a nucleotide receptor mediates the effects of extracellular ATP and UTP on phosphatidylcholine metabolism in rat cultured glomerular mesangial cells. 2. ATP and UTP stimulated a biphasic 1,2-diacylglycerol (DAG) formation in [3H]-arachidonic acid-labelled mesangial cells. In contrast, in cel...

    journal_title:British journal of pharmacology

    pub_type: 杂志文章


    authors: Pfeilschifter J,Merriweather C

    更新日期:1993-10-01 00:00:00

  • Pinacidil opens K+-selective channels causing hyperpolarization and relaxation of noradrenaline contractions in rat mesenteric resistance vessels.

    abstract::1. The effects of pinacidil on noradrenaline-induced tone, smooth muscle membrane potential and 42K- and 86Rb-efflux from isolated mesenteric resistance vessels (internal diameter 200 microns) of the rat have been studied. 2. Pinacidil (0.3-10 microM) produced concentration-dependent suppression of noradrenaline-induc...

    journal_title:British journal of pharmacology

    pub_type: 杂志文章


    authors: Videbaek LM,Aalkjaer C,Mulvany MJ

    更新日期:1988-09-01 00:00:00

  • The effect of -adrenoceptor blockade on human sweating.

    abstract::1. Changes in cutaneous water loss were followed by continuously monitoring total body weight loss.2. Sweating was induced in normal subjects by raising the environmental temperature or by subjecting them to the emotional stress of mental arithmetic.3. Propranolol in a dosage of 0.15 mg/kg body weight intravenously ha...

    journal_title:British journal of pharmacology

    pub_type: 杂志文章


    authors: Allen JA,Jenkinson DJ,Roddie IC

    更新日期:1973-03-01 00:00:00

  • The effects of acute and chronic lithium treatment on pilocarpine-stimulated phosphoinositide hydrolysis in mouse brain in vivo.

    abstract::1. Measurements were made of the in vivo formation of inositol phosphates in the brains of C57/B1/601a mice treated acutely or chronically with lithium chloride (LiCl). 2. A single injection of LiCl (10 mEquiv kg-1, s.c.) 18 h before death increased the accumulation of [3H]-inositol phosphates ([3H]-Ins P's) in the br...

    journal_title:British journal of pharmacology

    pub_type: 杂志文章


    authors: Whitworth P,Heal DJ,Kendall DA

    更新日期:1990-09-01 00:00:00

  • NCX4016 (NO-aspirin) reduces infarct size and suppresses arrhythmias following myocardial ischaemia/reperfusion in pigs.

    abstract::1. The effect of the nitro-derivative of aspirin, NCX4016, was assessed on ischaemic ventricular arrhythmias and myocardial infarct size in anaesthetized pigs in comparison to native aspirin. 2. Pigs were given aspirin (10 mg kg(-1); n=6), low dose NCX4016 (18.4 mg kg(-1); n=6) or high dose NCX4016 (60 mg kg(-1); n=7)...

    journal_title:British journal of pharmacology

    pub_type: 杂志文章


    authors: Wainwright CL,Miller AM,Work LM,Del Soldato P

    更新日期:2002-04-01 00:00:00

  • Moxifloxacin modifies corneal fibroblast-to-myofibroblast differentiation.

    abstract:BACKGROUND AND PURPOSE:Fibroblast-to-myofibroblast differentiation is associated with scarring, an important issue in corneal surgery. Moxifloxacin (MOX), commonly applied to prevent post-operative infection, would benefit more if it modifies fibroblast-to-myofibroblast differentiation other than antimicrobial activity...

    journal_title:British journal of pharmacology

    pub_type: 杂志文章


    authors: Chen TC,Chang SW,Wang TY

    更新日期:2013-03-01 00:00:00