n-methyl-d-aspartate-evoked striatal acetylcholine: Topics by WorldWideScience.org

Striatal dysfunction in attention deficit and hyperkinetic disorder

Recent studies have reported that cognitive inflexibility associated with impairments in a frontal-striatal circuit and parietal region is a core cognitive deficit of obsessive-compulsive disorder (OCD)....Full Text Available

2011-05-01

Organophosphate acetylcholine esterase inhibitor poisoning from a home-made shampoo

We have previously reported that periventricular structures are hypoperfused in attention deficit and hyperactivity disorder (ADHD). This study has expanded the number of patients, who were divided into two groups: six patients with pure ADHD, and 13 patients with ADHD in combination with other neurologic symptoms. By using xenon 133 inhalation and emission tomography, the regional cerebral blood flow distribution was determined and compared with a control group. Striatal regions were found to be hypoperfused and, by inference, hypofunctional in both groups. This hypoperfusion was statistically significant in the right striatum in ADHD, and in both striatal regions in ADHD with other neuropsychologic and neurologic symptoms. The primary sensory and sensorimotor cortical regions were highly perfused. Methylphenidate increased flow to striatal and posterior periventricular regions, and tended to decrease flow to primary ...

1989-01-01

Acetylcholine receptor kinetics. A description from single-channel currents at snake neuromuscular junctions.

Organophosphate acetylcholine esterase inhibitor poisoning is a major health problem in children. We report an unusual cause of organophosphate acetylcholine esterase inhibitor poisoning. Two children...Full Text Available

2011-07-01

Structure and function of an acetylcholine receptor.

Single-channel currents from acetylcholine receptor channels of garter snake neuromuscular junctions were recorded using the patch-clamp technique. Low concentrations of acetylcholine or carbamylcholine...Full Text Available

1982-09-01

Drug-induced changes in brain acetylcholine

Structural analysis of an acetylcholine receptor from Torpedo californica leads to a three-dimensional model in which a "monomeric" receptor is shown to contain subunits arranged around a central ionophoretic...Full Text Available

1982-01-01

Cholinergic modulation of multivesicular release regulates striatal synaptic potency and integration

In rats, drug-induced depression of the central nervous system has been shown generally to be associated with an elevation in level of total acetylcholine in the brain. This generalization held true...Full Text Available

1962-10-01

Relative potencies for barbiturate binding to the Torpedo acetylcholine receptor.

The pleiotropic actions of neuromodulators on pre- and postsynaptic targets present challenges to disentangling the mechanisms underlying regulation of synaptic transmission. Within the striatum,...Full Text Available

2009-09-01

In vitro selection of RNA molecules that displace cocaine from the membrane-bound nicotinic acetylcholine receptor

1. The structural requirements of an allosteric barbiturate binding site on acetylcholine receptor-rich membranes isolated from Torpedo electroplaques have been characterized by the ability of fourteen...Full Text Available

1990-11-01

Evidence for the Regulation of Phytochrome-mediated Processes in Bean Roots by the Neurohumor, Acetylcholine ¹

The nicotinic acetylcholine receptor (AChR) controls signal transmission between cells in the nervous system. Abused drugs such as cocaine inhibit this receptor. Transient kinetic investigations indicate...Full Text Available

1998-11-24

An analysis by low-angle neutron scattering of the structure of the acetylcholine receptor from Torpedo californica in detergent solution.

Using pharmacological and chromatographic techniques, it was shown that acetylcholine was present in all organs of both light- and dark-grown mung bean seedings (Phaseolus aureus)....Full Text Available

1970-12-01

Src Kinase Inhibition Decreases Thrombin Induced Injury and Cell Cycle Re-Entry in Striatal Neurons

The acetylcholine receptor from the electric tissue of Torpedo californica is a large, integral membrane protein containing four different types of polypeptide chains. The structure of the purified...Full Text Available

1979-12-01

Probing Compulsive and Impulsive Behaviors, from Animal Models to Endophenotypes: A Narrative Review

Since Src kinase inhibitors decrease brain injury produced by intracerebral hemorrhage (ICH) and thrombin is activated following ICH, this study determined whether Src kinase inhibitors decrease...Full Text Available

2008-05-01

Association of Protein Phosphatase 1?₁ with Spinophilin Suppresses Phosphatase Activity in a Parkinson Disease Model*

Failures in cortical control of fronto-striatal neural circuits may underpin impulsive and compulsive acts. In this narrative review, we explore these behaviors from the perspective of neural processes...Full Text Available

2010-02-01

A Kinetic Model of Dopamine- and Calcium-Dependent Striatal Synaptic Plasticity

Sustained nigrostriatal dopamine depletion increases the serine/threonine phosphorylation of multiple striatal proteins that play a role in corticostriatal synaptic plasticity, including Thr²⁸⁶...Full Text Available

2008-05-23

Structure and Characterization of Nicotinic Acetylcholine ...

Corticostriatal synapse plasticity of medium spiny neurons is regulated by glutamate input from the cortex and dopamine input from the substantia nigra. While cortical stimulation alone results in long-term...Full Text Available

2010-02-01

Acetylcholine Receptor Binding Characteristics of Snake and ...

... the ct-neurotoxin from Dendroaspis viridis venom (a-DTX) , which binds to four sites on the AcChR molecule (Conti-Tronconi & Raftery 1986). ...

1991-11-07

Separation of recycling and reserve synaptic vesicles from cholinergic nerve terminals of the myenteric plexus of guinea pig ileum.

... Naja oxiana neurotoxin 1, Bungarus multicinctus or-bungarotoxin) and short-chain group (Naja naja atra cobrotoxin, Naja oxiana neurotoxin 11. ...

2011-05-13

Rapid Respiratory Changes Due to Red Light or Acetylcholine during the Early Events of Phytochrome-mediated Photomorphogenesis ¹

Acetylcholine-rich synaptic vesicles were isolated from myenteric plexus-longitudinal muscle strips derived from the guinea pig ileum by the method of Dowe, Kilbinger, and Whittaker [J. Neurochem. 35, 993-1003 (1980)] using either unstimulated preparations or preparations field-stimulated at 1 Hz for 10 min using pulses of 1 ms duration and 10 V . cm-1 intensity. The organ bath contained either tetradeuterated (d4) choline (50 microM) or [3H]acetate (2 muCi . ml-1); d4 acetylcholine was measured by gas chromatography-mass spectrometry. As with Torpedo electromotor cholinergic vesicle preparations made under similar conditions the distribution of newly synthesized (d4 or [3H]) acetylcholine in the zonal gradient from stimulated preparations was not identical with that of endogenous (d0, [1H]) acetylcholine, but corresponded to a subpopulation of denser vesicles (equivalent to the VP2 fraction from ...

1985-01-01

Tone-Specific and Nonspecific Plasticity of the Auditory Cortex Elicited by Pseudoconditioning: Role of Acetylcholine Receptors and the Somatosensory Cortex

Two millimeter long secondary root tips of etiolated mung bean (Phaseolus aureus) plants were given 4 minute consecutive treatments of darkness, red light, far red light, and acetylcholine...Full Text Available

1972-01-01

Parallel helix bundles and ion channels: molecular modeling via simulated annealing and restrained molecular dynamics.

Experience-dependent plastic changes in the central sensory systems are due to activation of both the sensory and neuromodulatory systems. Nonspecific changes of cortical auditory neurons elicited by...Full Text Available

2008-09-01

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New insights into purinergic receptor signaling in neuronal differentiation, neuroprotection, and brain disorders

A parallel bundle of transmembrane (TM) alpha-helices surrounding a central pore is present in several classes of ion channel, including the nicotinic acetylcholine receptor (nAChR). We have modeled...Full Text Available

1994-10-01

Long-term cortical plasticity evoked by electric stimulation and acetylcholine applied to the auditory cortex

Ionotropic P2X and metabotropic P2Y purinergic receptors are expressed in the central nervous system and participate in the synaptic process particularly associated with acetylcholine, GABA, and glutamate...Full Text Available

2007-09-01

In silico modeling of the specific inhibitory potential of thiophene-2,3-dihydro-1,5-benzothiazepine against BChE in the formation of ?-amyloid plaques associated with Alzheimer's disease

Auditory fear conditioning with tone bursts followed by electric leg stimulation activates neurons not only in the auditory and somatosensory systems but also in many other regions of the brain and...Full Text Available

2005-06-28

Immunoglobulins in myasthenia gravis. Kinetic properties of the acetylcholine-receptor antibody studied during lymph drainage.

BackgroundAlzheimer's disease, known to be associated with the gradual loss of memory, is characterized by low concentration of acetylcholine in the hippocampus and cortex part of...Full Text Available

Continuous monitoring of receptor-mediated changes in the metabolic rates of living cells.

A specific immunoglobulin, the receptor antibody, can be found in most patients with myasthenia gravis. In order to study the kinetic properties of this antibody, serial determinations of receptor antibody,...Full Text Available

1978-10-01

Attenuation of Cocaine's Reinforcing and Discriminative Stimulus Effects via Muscarinic M₁ Acetylcholine Receptor StimulationS?

Activation of beta-adrenergic or muscarinic acetylcholine receptors expressed in transfected cells or epidermal growth factor receptors in human keratinocytes produces 15% to 200% changes in cellular...Full Text Available

1990-05-01

Muscarinic and nicotinic activities of the novel acetylcholine analog acetylselenonium choline.

Muscarinic cholinergic receptors modulate dopaminergic function in brain pathways thought to mediate cocaine's abuse-related effects. Here, we sought to confirm and ...Full Text Available

2010-01-01

Botulinum toxin—Beyond wrinkles

The present paper further characterizes the cholinergic properties of acetylselenonium choline (ASeCh, (CH3)2Se+CH2CH2OCOCH3). The data demonstrate that ASeCh possesses muscarinic receptor agonist properties as evidenced by vasodepressor and smooth muscle contractile activities which are enhanced by physostigmine and antagonized by atropine. ASeCh also possessed nicotinic agonist activity on frog rectus abdominis tissue which was potentiated by physostigmine, and blocked by d-tubocurarine. The relative potencies of ASeCh ranged from approximately 1% to approximately 6% of the potency of acetylcholine in the three types of preparations examined. PMID:1435078

1992-01-01

British Library Electronic Table of Contents (United Kingdom)

Botulinum neurotoxin is produced by the bacterium, Clostridium botulinum. The neurotoxin inhibits acetylcholine at the neuromuscular junction, thus interfering with overall muscular contraction. Botulinum neurotoxin is commonly used for the following medical conditions: cervical dystonia, upper limb spasticity, blepharospasm, strabismus, and hyperhydrosis. However, the use of botulinum neurotoxin was recently approved for the prophylaxis of headaches in adults with chronic migraines. The proposed mechanism of botulinum neurotoxin is no longer solely limited to the inhibition of acetylcholine. There are new mechanisms emerging that involve inhibition of proinflammatory agents and neuropeptides involved in chronic pain. Consequently, there is a disruption of the overall sensory feedback loop...

2011-01-01

Cholinergic systems in brain development and disruption by neurotoxicants: nicotine, environmental tobacco smoke, organophosphates

Targeting the nicotinic alpha7 acetylcholine receptor to enhance cognition in disease

Acetylcholine and other neurotransmitters play unique trophic roles in brain development. Accordingly, drugs and environmental toxicants that promote or interfere with neurotransmitter function evoke neurodevelopmental abnormalities by disrupting the timing or intensity of neurotrophic actions. The current review discusses three exposure scenarios involving acetylcholine systems: nicotine from maternal smoking during pregnancy, exposure to environmental tobacco smoke (ETS), and exposure to the organophosphate insecticide, chlorpyrifos (CPF). All three have long-term, adverse effects on specific processes involved in brain cell replication and differentiation, synaptic development and function, and ultimately behavioral performance. Many of these effects can be traced to the sequence of cellular events surrounding the trophic role of acetylcholine acting on its specific cellular receptors and associated signaling cascades. ...

2004-07-15

British Library Electronic Table of Contents (United Kingdom)

A promising drug target currently under investigation to improve cognitive deficits in neuropsychiatric and neurological disorders is the neuronal nicotinic alpha7 acetylcholine receptor (a7nAChR). Improving cognitive impairments in diseases such as Alzheimer's (AD) and schizophrenia remains a large unmet medical need, and the a7nAChR has many properties that make it an attractive therapeutic target. The a7nAChR is a ligand gated ion channel that has particularly high permeability to Ca^2^+ and is expressed in key brain regions involved in cognitive processes (e.g., hippocampus). The a7nAChRs are localized both pre-synaptically, where they can regulate neurotransmitter release, and post-synaptically where they can activate intracellular signaling cascades and influence downstream processes...

2011-01-01

Research update: Alpha7 nicotinic acetylcholine receptor mechanisms in Alzheimer's disease

British Library Electronic Table of Contents (United Kingdom)

Aberrant amyloid-b peptide (Ab) accumulation along with altered expression and function of nicotinic acetylcholine receptors (nAChRs) stand prominently in the etiology of Alzheimer's disease (AD). Since the discovery that Ab is bound to a7 nAChRs under many experimental settings, including post-mortem AD brain, much effort has been expended to understand the implications of this interaction in the disease milieu. This research update will review the current literature on the a7 nAChR-Ab interaction in vitro and in vivo, the functional consequences of this interaction from sub-cellular to cognitive levels, and discuss the implications these relationships might have for AD therapies.

2011-01-01

Single Particle Tracking of ?7 Nicotinic AChR in Hippocampal Neurons Reveals Regulated Confinement at Glutamatergic and GABAergic Perisynaptic Sites

Cloning and mapping of the mouse {alpha}7-neuronal nicotinic acetylcholine receptor

α7 neuronal nicotinic acetylcholine receptors (α7-nAChR) form Ca²⁺-permeable homopentameric channels modulating cortical network activity and cognitive processing....Full Text Available

Radiolabelling of. cap alpha. -bungarotoxin to high specific radioactivity with complete retention of biological activity

We report the isolation of cDNA clones for the mouse {alpha}7 neuronal nicotinic acetylcholine receptor subunit (gene symbol Acra7), the only nicotinic receptor subunit known to bind a-bungarotoxin in mammalian brain. This gene may have relevance to nicotine sensitivity and to some electrophysiologic findings in schizophrenia. The mouse {alpha}7 subunit gene encodes a protein of 502 amino acids with substantial identity to the rat (99.6%), human (92.8%), and chicken (87.5%) amino acid sequences. The {alpha}7 gene was mapped to mouse chromosome 7 near the p locus with the following gene order from proximal to distal: Myod1-3.5 {+-}1.7 cM-Gas2-0.9 cM {+-} 0.9 cM-D7Mit70-1.8 {+-} 1.2 cM- Acra7-4.4 {+-}1.0 cM-Hras1-ps11/Igf1r/Snrp2a. The human gene was confirmed to map to the homologous region of human chromosome 15q13-q14. 26 refs., 3 figs.

1995-03-20

Acute low-level microwave exposure and central cholinergic activity: studies on irradiation parameters

Radioiodinated ..cap alpha..-bungarotoxin, the venom of Bungarus multicinctus, is commonly used for the detection and quantification of nicotinic acetylcholine receptors (nAChR) and anti-nAChR antibodies. A radioiodination method is described which is simple and yields a fully active product which, after fractionation, has a specific activity tenfold higher (900 Ci/mmol) than those routinely used, resulting in enhanced sensitivity of assays and conservation of material, especially muscle extracts.

1984-10-01

The effect of the venom of the yellow Iranian scorpion Odontobuthus doriae on skeletal muscle preparations in vitro

Sodium-dependent high-affinity choline uptake was measured in the striatum, frontal cortex, hippocampus, and hypothalamus of rats after acute exposure (45 min) to pulsed (2 microseconds, 500 pps) or continuous-wave 2,450-MHz microwaves in cylindrical waveguides or miniature anechoic chambers. In all exposure conditions, the average whole-body specific absorption rate was at 0.6 W/kg. Decrease in choline uptake was observed in the frontal cortex after microwave exposure in all of the above irradiation conditions. Regardless of the exposure system used, hippocampal choline uptake was decreased after exposure to pulsed but not continuous-wave microwaves. Striatal choline uptake was decreased after exposure to either pulsed or continuous-wave microwaves in the miniature anechoic chamber. No significant change in hypothalamic choline uptake was observed under any of the exposure conditions studied. We conclude that depending on the parameters of the radiation, ...

1988-01-01

British Library Electronic Table of Contents (United Kingdom)

The yellow Iranian scorpion Odontobuthus doriae can cause fatal envenoming, but its mechanism of action is unclear. One of the reported manifestations of envenoming is moderate to severe involuntary tremor of skeletal muscle. In order to understand better the mechanism of action of this venom on skeletal muscle function, we examined the effects of the venom in vitro on chick biventer cervicis (CBC) and mouse hemidiaphragm (MHD) nerve muscle preparations. O. doriae venom (0.3-10mg/ml) initially increased and then decreased twitch height. The venom also caused contracture in both preparations. In mouse triangularis sterni preparations, used for all intracellular recording techniques, the venom enhanced the release of acetylcholine and induced repetitive firing of nerve action potentials and ...

2007-01-01

Synthesis of novel tellurium containing analogues of choline and acetylcholine and their quantitation by pyrolysis-gas chromatography-mass spectrometry.

The neuronal nicotinic acetylcholine receptor {alpha}7 subunit gene: Cloning, mapping, structure, and targeting in mouse

Methods for the synthesis and quantitation of the novel choline analogues, telluronium choline and acetyltelluronium choline, are described. An assay procedure utilizing pyrolysis-gas chromatography-mass spectrometry (Py-GC-MS) with cold trapping was developed with [2H4]telluronium choline and [2H4]acetyltelluronium choline as internal standards. The telluronium compounds were ion-pair extracted from tissue with dipicrylamine, washed with 2-butanone, and pyrolyzed prior to GC-MS analysis. The compounds were monitored using selected ion monitoring at m/z 232 and m/z 190 for acetyltelluronium and telluronium choline, respectively, and at m/z 236 and m/z 194 for the analogous deuterated internal standards. The assay was linear over a range of 20 pmol-20 nmol of compound taken through the assay. PMID:8130881

1993-12-31

Structural determinants of alpha-bungarotoxin binding to the sequence segment 181-200 of the muscle nicotinic acetylcholine receptor #alpha# subunit: Effects of cysteine/cystine modification and species-specific amino acid substitution

The neuronal nicotinic acetylcholine receptor {alpha}7 subunit is a member of a family of ligand-gated ion channels, and is the only subunit know to bind {alpha}-bungarotoxin in mammalian brain. {alpha}-Bungarotoxin binding sites are known to be more abundant in the hippocampus of mouse strains that are particularly sensitive to nicotine-induced seizures. The {alpha}7 receptor is highly permeable to calcium, which could suggest a role in synaptic plasticity in the nervous system. Auditory gating deficiency, an abnormal response to a second auditory stimulus, is characteristic of schizophrenia. Mouse strains that exhibit a similar gating deficit have reduced hippocampal expression of the {alpha}7 subunit. We have cloned and sequenced the full length cDNA for the mouse {alpha}7 gene (Acra-7) and characterized its gene structure. The murine {alpha}7 shares amino acid identity of 99% and 93% with the rat and human {alpha}7 subunits, respectively. Using an interspecies ...

1994-09-01

Kainate-enhanced release of D-(3H)aspartate from cerebral cortex and striatum: reversal by baclofen and pentobarbital

The sequence segment 181-200 of the Torpedo nicotinic acetylcholine receptor (nAChR) #alpha#subunit forms a binding site for #alpha#-bungarotoxin (#alpha#-BTX). Synthetic peptides corresponding to the homologous sequences of human, calf, mouse, chicken, frog, and cobra muscle nAChR #alpha#1 subunits were tested for their ability to bind "1"2"5I-#alpha#-BTX, and differences in #alpha#-BTX affinity were determined by using solution (IC_5_0s) and solid-phase (K_ds) assays. Panels of overlapping peptides corresponding to the complete #alpha#1 subunit of mouse and human were also tested for #alpha#-BTX binding, but other sequence segments forming the #alpha#-BTX site were not consistently detectable. The role of a putative vicinal disulfide bound between Cys-192 and -193, relative to the Torpedo sequence, was determined by modifying the peptides with sulfhydryl reagents. Reduction and alkylation of the peptides decreased #alpha#-BTX binding, whereas oxidation of the ...

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[Molecular cloning and expression of an isotoxin gene, alpha-bungarotoxin, from Bungarus multicinctus].

A study was made of the actions of the excitant neurotoxin, kainic acid, on the uptake and the release of D-(2,3-3H)aspartate (D-ASP) in slices of guinea pig cerebral neocortex and striatum. The slices took up D-ASP, reaching concentrations of the amino acid in the tissue which were 14-23 times that in the medium. Subsequently, electrical stimulation of the slices evoked a Ca2+-dependent release of a portion of the D-ASP. Kainic acid (10(-5)-10(-3) M) produced a dose-dependent inhibition of D-ASP uptake. The electrically evoked release of D-ASP was increased 1.6-2.0 fold by 10(-5) and 10(-4)M kainic acid. The kainate-enlarged release was Ca2+-dependent. Dihydrokainic acid, an analogue of kainic acid with little excitatory or toxic action, did not increase D-ASP release but depressed D-ASP uptake. Attempts were made to block the action of kainic acid with baclofen and pentobarbital, compounds which depress the electrically evoked release of L-glutamate (L-GLU) and L-aspartate (L-ASP). ...

1983-06-01

Short-term regulation of muscarinic acetylcholine receptors: An assessment utilizing mouse brain and mouse neuroblastoma cells

Abstract: Snake venom contains a number of small proteins,enzymes and other components,which displays a broad spectrum of biological activities. With the ability of specifically binding on acetylcholine acceptor, alpha-bungarotoxins are not only useful molecular probes in investigating the mechanism of neural signal transmission, but also potential pharmic preparations for neural disease treatment. In current research,cDNAs of Bungarus multicinutus venom gland were synthesized using SMART cDNA amplification kit and then, alpha-bungarotoxin genes were cloned and sequenced. Total of 20 clones were sequenced representing 14 isotoxin mRNAs of alpha-bungarotoxins. Among those clones, a novel isotoxin gene was subcloned into two expression plasmids, alpha-BgTX/pQE30a and alpha-BgTX/pGEX-4T-1, and transformed into E. coli. After inducing with IPTG, fused protein of GST-alpha-BgTX was successfully expressed at level of 30% gross proteins of bacteria. More than 25% of fused ...

2005-07-01

Plasma membrane as the target site of cholic acid analogs.

The effects of muscarinic agonists and diisopropylfluorophosphate (DFP) on muscarinic receptor density and muscarinic receptor-mediated responses was assessed in mouse brain and mouse neuroblastoma cells (clone N1E-115). Utilizing the antagonist ({sup 3}H)quinuclidinyl benzilate (({sup 3}H)QNB), there was no difference in the maximal binding capacity (B{sub max}) or equilibrium dissociation constant (K{sub d}) between untreated and 24 hour DFP-treated mice. However, one administration of DFP produced a 24% and 33% decrease in B{sub max} measured by ({sup 3}H)N-methylscopolamine (({sup 3}H)NMS) after 18 and 24 hours which was rapidly reversible within 36 hours after DFP treatment. The loss of ({sup 3}H)NMS binding sites following acute DFP treatment was not accompanied by a change in a particular muscarinic receptor binding conformation. Furthermore, the magnitude of muscarinic receptor-mediated phosphoinositide hydrolysis was unchanged following short-term DFP treatment.

1988-01-01

Effects of chronic treatment with honokiol in spontaneously hypertensive rats.

Although the mechanism is unknown, Calculus Bovis and its active components, cholic acid analogs (CAAs), have been used in China to treat a wide range of diseases. Based on the previous finding that the potency of CAA is strongly dependent on the intrinsic surface activity, this paper aimed to investigate the role of the plasma membrane in the pharmacological activity of CAAs. First, CAAs (0.1 mM) caused a surface activity-dependent depression on ATPase activity in the cell membrane extract, but it had no effects on other cellular extracts, suggesting an indispensable role of the membrane environment for pharmacological activity. Second, CAAs lowered the membrane fluidity of cultured Caco-2 cells with the same rank-order of potency sequence. Third, the hypothesis that any functional protein located on the membrane is influenced by changes in cellular membrane fluidity was supported by: ileal contraction that was induced by acetylcholine and mediated by the ...

2011-08-03

Conditions for the selective labelling of the 66 000 dalton chain of the acetylcholine receptor by the covalent non-competitive blocker 5-azido-["3H]trimethisoquin

The present study was performed to evaluate the antihypertensive effects of honokiol in vivo in spontaneously hypertensive rats (SHR). The effects of honokiol were investigated by determination of the blood pressure, vascular reactivity, oxidative parameters, and histologic change in the aorta. Long-term administration of honokiol (400 mg/kg/d) to SHR decreased systolic blood pressure significantly. Honokiol (200, 400 mg/kg/d) enhanced the aortic relaxation in response to acetylcholine after 49-d treatment, but had no significant effects on the relaxation to sodium nitroprusside. The oral administration of honokiol significantly increased the plasma level of NO(2(-))/NO(3(-)), but decreased the level of malondialdehyde in liver of SHR compared with the control vehicle. In addition, SHR administered honokiol showed significant reductions in the elastin bands and media thickness in the aorta. These results suggest that chronic treatment with honokiol exerts an ...

2010-01-01

CHRNA5 as negative regulator of nicotine signaling in normal and cancer bronchial cells: effects on motility, migration and p63 expression

A photoaffinity derivative of the local anesthetic trimethisoquin, 5-azido-["3H]trimethisoquin (5-A["3H]T) labelled bands of app. mol. wt 50 k and 66 k. To explain the rather paradoxical labelling by 5-A["3H]T of two polypeptide chains instead of one, three possibilities were considered: (i) The site for non-competititve blockers is not carried by the 50 k or 66 k chain; however, these chains lie in the vicinity of the binding site and become preferentially labelled since they present chemical groups with which the nitrene group of 5-A["3H]T reacts. (ii) The 50 k and 66 k chains are different but carry binding sites for non-competitive blockers with similar reactivities. (iii) The 50 k chain labelled by 5-A["3H]T derives from the 66 k chain by proteolysis. These results show that the third alternative is the correct one. Under conditions which limit proteolysis, 5-A["3H]T selectively labels the 66 k polypeptide chain. (Auth.).

British Library Electronic Table of Contents (United Kingdom)

Genome-wide association studies have linked lung cancer risk with a region of chromosome 15q25.1 containing CHRNA3, CHRNA5 and CHRNB4 encoding a3, a5 and b4 subunits of nicotinic acetylcholine receptors (nAChR), respectively. One of the strongest associations was observed for a non-silent single-nucleotide polymorphism at codon 398 in CHRNA5. Here, we have used pharmacological (antagonists) or genetic (RNA interference) interventions to modulate the activity of CHRNA5 in non-transformed bronchial cells and in lung cancer cell lines. In both cell types, silencing CHRNA5 or inhibiting receptors containing nAChR a5 with a-conotoxin MII exerted a nicotine-like effect, with increased motility and invasiveness in vitro and increasing calcium influx. The effects on motility were enhanced by addit...

2011-01-01

Uptake of radiolabeled ions in normal and ischemia-damaged brain

Radioiodination of 3-quinuclidinyl benzilate using a no-carrier-added concentration of iodine-125/sodium-iodine

The regional concentrations of nine radiochemicals were measured in rat brain after induction of cerebral ischemia to identify tracers concentrated by brain undergoing selective neuronal necrosis. Transient (30 minute) forebrain ischemia was produced in the rat; 24 hours after cerebral recirculation the radiochemicals were injected intravenously and allowed to circulate for 5 hours. The brain concentrations of the radiochemicals in dissected regions were determined by scintillation counting. Forebrain ischemia of this nature will produce extensive injury to striatal neurons but will spare the great majority of neocortical neurons at 24 hours. The regional concentrations of these radiochemicals varied considerably in both control and ischemic animals. In postischemic animals, 4 radionuclides (/sup 63/Ni, /sup 99/TcO/sub 4/, /sup 22/Na, and (/sup 3/H)tetracycline) were concentrated in the irreversibly damaged striatum in amounts ranging from 1.4 to 2.4 times greater ...

1986-05-01

Prevention of physostigmine-, DFP-, and diazinon-induced acute toxicity by monoethylcholine and N-aminodeanol.

3-Quinuclidinyl benzilate (QNB) is a potent muscarinic antagonist that binds to muscarinic acetylcholine receptors. Iodination of QNB is difficult because it contains rings that are deactivated, while phenol rings are activated. The purpose of this research is to develop an appropriate method for the iodination of QNB at no-carrier-added concentrations of /sup 125/I/NaI. Phenol was chose as the test compound for direct iodination by adding chloramine T and nonradioactive sodium iodide to the phenol in a phosphate buffer and methanol system. A simple method to radioiodinate QNB at several concentrations was developed in situ in the presence of QNB, thallic trifluoroacetate /sup 125/I/NaI, /sup 127/I/NaI, and aluminium chloride. Using milligram amounts of QNB (7.12 x 10/sup -6/ moles), three reaction steps were involved: QNB was reacted with thallic trifluoroacetate at 60/sup 0/C for 24 hours, then radioactive /sup 125/I/NaI and aluminium chloride were added to the ...

1986-01-01

Neuromuscular effects of candoxin, a novel toxin from the venom of the Malayan krait (Bungarus candidus).

1. Choline, and the choline analogues monoethylcholine (MEC) and N-aminodeanol (NAD) were examined for prophylactic activity in acute acetylcholinesterase inhibitor toxicity in mice. The rank order of potency of the compounds was MEC greater than NAD greater than choline. 2. Simultaneous administration of MEC (60 mg kg-1) or NAD (200 mg kg-1) with physostigmine reduced lethality to 17 and 13% respectively. MEC (60 mg kg-1) completely protected against disopropylfluorophosphate (DFP) and diazinon toxicity, and NAD reduced lethality to 17% for both agents. Choline (200 mg kg-1) exhibited only negligible antidotal activity against the inhibitors. 3. In vitro concentrations of choline, MEC, and NAD, similar to the estimated concentration obtained in vivo in the acute toxicity study, produced mixed inhibition of mouse brain acetylcholinesterase. The inhibition was dose-related and was additive to the inhibition produced by the cholinesterase inhibitors. 4. All three analogues reduced ligand ...

1989-06-01

Cold pressor test myocardial perfusion SPECT as a predictor of the development of ischemia at exercise in the follow up of asymptomatic patients with moderate cardiovascular risk

1 Candoxin (MW 7334.6), a novel toxin isolated from the venom of the Malayan krait Bungarus candidus, belongs to the poorly characterized subfamily of nonconventional three-finger toxins present in Elapid venoms. The current study details the pharmacological effects of candoxin at the neuromuscular junction. 2 Candoxin produces a novel pattern of neuromuscular blockade in isolated nerve-muscle preparations and the tibialis anterior muscle of anaesthetized rats. In contrast to the virtually irreversible postsynaptic neuromuscular blockade produced by curaremimetic alpha-neurotoxins, the neuromuscular blockade produced by candoxin was rapidly and completely reversed by washing or by the addition of the anticholinesterase neostigmine. 3 Candoxin also produced significant train-of-four fade during the onset of and recovery from neuromuscular blockade, both, in vitro and in vivo. The fade phenomenon has been attributed to a blockade of putative presynaptic nicotinic ...

2003-06-01

Ophidian envenomation strategies and the role of purines.

Introduction: Previous studies have published the correlation between myocardial perfusion SPECT (MP) during cold pressor test (CPT) and intracoronary acetylcholine and its usefulness as independent marker of endothelial dysfunction (ED). Objective: To analyze the incidence of positivization of MP exercise studies in the follow up of asymptomatic patients with moderate cardiovascular risk (CV) and ED detected by PF. Material and Methods: Of 301 patients of the PARADIGMA Registry (normal exercise MP SPECT and clinical probability < 20% of events at 10 years [moderate risk by Framingham index]) 55 had positive PF (+) (18.3%). Prospectively and consecutively, 15 asymptomatic patients with PF (+), and a control group (CG) of 15 patients with negative PF, with paired sex, age and coronary risk factors (CRF), that accomplished a 12 #+-# 2 months follow up, and that underwent a new exercise and resting MP SPECT were analyzed. An MP extension score was used in a model ...