a7 nicotinic acetylcholine: Topics by WorldWideScience.org

Structure and Characterization of Nicotinic Acetylcholine ...

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

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

... 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

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

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

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

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

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

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

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

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

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 ...

2004-07-15

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

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

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

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

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 ...

1994-09-01

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

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 ...

Variation in Nicotine Consumption in Inbred Mice Is Not Linked to Orosensory Ability

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

The effects of nicotine, hexamethonium and ethanol on the secretion of the antidiuretic and oxytocic hormones of the rat

Genetic studies of nicotine addiction in mice have utilized the oral self-administration model. However, it is unclear if strain differences in nicotine consumption are influenced by variation in bitter...Full Text Available

2009-01-01

Organophosphate acetylcholine esterase inhibitor poisoning from a home-made shampoo

The actions of nicotine, hexamethonium, and ethanol on the hypothalamo-hypophysial system have been investigated in the rat. The antidiuretic action of nicotine was not inhibited by ethanol, nor by...Full Text Available

1957-12-01

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

Naltrexone Inhibits Catecholamine Secretion Evoked by Nicotinic Receptor Stimulation in the Perfused Rat Adrenal Medulla

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

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KoreaScience (Korea)

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2005-08-01

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

Prosocial effects of nicotine and ethanol in adolescent rats through partially dissociable neurobehavioral mechanisms

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

Noradrenergic ?₁ Receptors as a Novel Target for the Treatment of Nicotine Addiction

2009-11-01

Female rats display dose-dependent differences to the rewarding and aversive effects of nicotine in an age-, hormone-, and sex-dependent manner

Nicotine is the main psychoactive ingredient in tobacco and its rewarding effects are considered primarily responsible for persistent tobacco smoking and relapse. Although dopamine has been extensively...Full Text Available

2010-07-01

Relative potencies for barbiturate binding to the Torpedo acetylcholine receptor.

IntroductionThe objective of this study was to examine age-, hormone-, and sex-dependent differences to the behavioral effects of nicotine using place-conditioning...Full Text Available

2009-10-01

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

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

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

Prosocial effects of nicotine and ethanol in adolescent rats through partially dissociable neurobehavioral mechanisms

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

Environmental tobacco smoke and sudden infant death syndrome: a review

The widespread use of tobacco and alcohol among adolescents might be related to the ability of nicotine and ethanol to facilitate social interactions. To investigate the neurobehavioral mechanisms underlying the prosocial effects of nicotine and ethanol, we focused on social play behavior, the most characteristic social activity in adolescent rats. Social play behavior is rewarding, and it is modulated through opioid, cannabinoid and dopaminergic neurotransmission, which are also involved in the reinforcing properties of nicotine and ethanol. We found that nicotine and ethanol increased social play, without affecting locomotion or social exploration. Their effects depended on the level of social activity of the partner, and were comparable in familiar and unfamiliar environments. At doses that increased social play, nicotine and ethanol had no anxiolytic effects in the elevated ...

2009-08-05

British Library Electronic Table of Contents (United Kingdom)

Environmental tobacco smoke (ETS), containing the developmental neurotoxicant, nicotine, is a prevalent component of indoor air pollution. Despite a strong association with active maternal smoking and sudden infant death syndrome (SIDS), information on the risk of SIDS due to prenatal and postnatal ETS exposure is relatively inconsistent. This literature review begins with a discussion and critique of existing epidemiologic data pertaining to ETS and SIDS. It then explores the biologic plausibility of this association, with comparison of the known association between active maternal smoking and SIDS, by examining metabolic and placental transfer issues associated with nicotine, and the biologic responses and mechanisms that may follow exposure to nicotine. Evidence indicates that prenatal ...

2006-01-01

Nicotine and periodontal tissues

Acetylcholine Receptor Binding Characteristics of Snake and ...

Tobacco use has been recognized to be a significant risk factor for the development and progression of periodontal disease. Its use is associated with increased pocket depths, loss of periodontal attachment,...Full Text Available

2010-01-01

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

Correspondence of interactive voice response (IVR) reports of nicotine withdrawal, craving, and negative mood with questionnaire ratings

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

British Library Electronic Table of Contents (United Kingdom)

This study focuses on comparing reports of nicotine withdrawal, craving, and depressive symptoms obtained using an Interactive Voice Response (IVR) system and several questionnaires. As part of a smoking cessation trial, daily reports of withdrawal, craving, and negative mood were collected using an IVR system for 7 days after participants attempted to quit smoking, and several pencil and paper questionnaires (i.e., the Minnesota Nicotine Withdrawal Scale, the Questionnaire on Smoking Urges, and the Center for Epidemiological Studies-Depression) were completed a week after the target quit date. The sample was composed of 378 daily smokers. Moderate to high correlations were found between the research questionnaires obtained at the end of the week and the corresponding daily IVR reports of ...

2008-01-01

Temporal Stability of Urinary and Plasma Biomarkers of Tobacco Smoke Exposure among Cigarette Smokers

Stable Isotope-Coded Quaternization for Comparative Quantification of Estrogen Metabolites by High-Performance Liquid Chromatography-Electrospray Ionization Mass Spectrometry

Intraindividual variability of measurements of 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanol (NNAL), nicotine, cotinine, and r-1,t-2,3,c-4-tetrahydroxy-1,2,3,4-tetrahydrophenanthrene...Full Text Available

2010-06-01

Smoking and Illicit Drug Use Associations With Early Versus Delayed Reproduction: Findings in a Young Adult Cohort of Australian Twins*

A fast and sensitive LC-ESI-MS method is described for the comparative quantification of 16 estrogen metabolites based on the derivatization of estrogens with a novel derivatizing reagent, N-methyl-nicotinic...Full Text Available

2008-07-15

Mouse model predicts effects of smoking and varenicline on event-related potentials in humans

Objective:This article examines relationships between reproductive onset and lifetime history of smoking, regular smoking, and nicotine dependence, and cannabis and other illicit...Full Text Available

2009-09-01

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

Background:Nicotine alters auditory event-related potentials (ERPs) in rodents and humans and is an effective treatment for smoking cessation. Less is known about the effects of...Full Text Available

2010-06-01

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

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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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

Botulinum toxin—Beyond wrinkles

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

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

Genetic analysis of the psychostimulant effects of nicotine in chromosome substitution strains and F2 crosses derived from A/J and C57BL/6J progenitors

British Library Electronic Table of Contents (United Kingdom)

Previous research utilizing the AcB/BcA recombinant congenic strains (RCS) of mice mapped provisional quantitative trait loci (QTLs) for the psychostimulant effects of nicotine to multiple regions on chromosomes 7, 11, 12, 14, 16, and 17. The current study was designed to confirm these QTLs in an A/J (A)??C57Bl/6J (B6) F2 cross and a panel of B6.A chromosome substitution strains (CSS). The panel of B6.A CSS consists of 21 strains, each carrying a different A/J chromosome on a B6 background. The A??B6 F2, CSS, A, and B6 mice were tested for sensitivity to the effects of nicotine on locomotor activity using a computerized open-field apparatus. In A??B6 F2 mice two QTLs were identified which confirm those previously observed in the AcB/BcA RCS. Significant differences in the expression of ...

2009-01-01

An open-label study of naltrexone and bupropion combination therapy for smoking cessation in overweight and obese subjects

British Library Electronic Table of Contents (United Kingdom)

A combination of sustained release (SR) naltrexone (32mg/day) and bupropion SR (360mg/day) plus behavioral counseling was evaluated for the treatment of smoking cessation and mitigation of nicotine withdrawal and weight gain. Thirty overweight or obese nicotine-dependent subjects were enrolled in a 24-week, open-label study; 85% and 63% completed 12 and 24weeks, respectively. The target quit date was Week 4. Week 4-12 continuous abstinence rate was 48%, 78% of subjects achieved CO 10ppm, serum cotinine decreased from 185 to 48mg/L, and tobacco use decreased from 129 to 14 cigarettes/week. Similar results were seen at Week 24. Body weight was essentially unchanged (Week 12: -0.1%; Week 24: +0.4%). Except for a transient significant increase 1week after the target quit date (p<0.05), nicotin...

2010-01-01

Nicotine Fast Dissolving Films Made of Maltodextrins: A Feasibility Study

British Library Electronic Table of Contents (United Kingdom)

This work aimed to develop a fast-dissolving film made of low dextrose equivalent maltodextrins (MDX) containing nicotine hydrogen tartrate salt (NHT). Particular attention was given to the selection of the suitable taste-masking agent (TMA) and the characterisation of the ductility and flexibility under different mechanical stresses. MDX with two different dextrose equivalents (DEs), namely DE 6 and DE 12, were selected in order to evaluate the effect of polymer molecular weight on film tensile properties. The bitterness and astringency intensity of NHT and the suppression effect of several TMA were evaluated by a Taste-Sensing System. The films were characterised in term of NHT content, tensile properties, disintegration time and drug dissolution test. As expected, placebo films made of ...

2010-01-01

Comparison of Plasma Antioxidant Levels and Related Metabolic Parameters Between Smokers and Non-smokers

British Library Electronic Table of Contents (United Kingdom)

The relationship between cigarette smoking and cell damage is complicated, particularly considering the role of oxidative stress. The aim of this study was to identify the relationships among plasma nicotine metabolites, lipophilic antioxidants, and metabolic parameters in smokers and non-smokers. This cross-sectional study recruited 100 subjects who visited the Department of Family Medicine at Kaohsiung Medical University Hospital. Excluding 14 ineligible cases, 46 smokers and 40 non-smokers were enrolled. Plasma nicotine metabolites, lipophilic antioxidants (including retinol, lycopene, a-carotene, b-carotene, d-tocopherol, g-tocopherol and a-tocopherol), related metabolic parameters, and body composition (including height, weight, body mass index, body fat, and waist circumference) were...

2009-01-01

N-acetylaspartylglutamate (NAAG) Inhibits Intravenous Cocaine Self-Administration and Cocaine-Enhanced Brain-Stimulation Reward in Rats

Targeting the kynurenine pathway as a potential strategy to prevent and treat Alzheimer's disease

Pharmacological activation of group II metabotropic glutamate (mGlu2 and mGlu3) receptors inhibits reward-seeking behavior and/or rewarding efficacy induced by drugs (cocaine, nicotine) or natural...Full Text Available

2010-01-01

British Library Electronic Table of Contents (United Kingdom)

Alzheimer's disease (AD) is a progressive neurodegenerative disorder of the elderly accounting for the vast majority of dementia. Recently, many studies have implicated the role of inflammatory response, especially neuroinflammatory response in the development and progression of AD. However, the underlying mechanism of how inflammatory response induces AD is unknown. Kynurenine pathway is a major route of the amino acid tryptophan catabolism, resulting in the production of nicotine adenine dinucleotide and other neuroactive intermediates: quinolinic acid (QA) and kynurenic acid (KA). QA exerts different toxic effects, including over-activation of N-methyl-d-aspartate (NMDA) receptor and excitotoxicity, synaptic dysfunction and neuronal death. On the other hand, KA is identified as the only...

2011-01-01

Exogenous nicotine normalises sensory gating in schizophrenia; therapeutic implications

British Library Electronic Table of Contents (United Kingdom)

Summary There is a current popular recognition that cigarette smoking is deleterious to health. Although this is very clearly the case for physical health, the situation regarding mental health is, however, rather more complicated. This piece concentrates on the role of smoking in schizophrenia: it is important to consider why schizophrenia, exceptionally amongst the severe and enduring mental illnesses, is associated with increased cigarette consumption. People who suffer from schizophrenia consequently have a greater risk of the complications to physical health caused by this addiction and clearly, it is important to understand why this occurs. Numerous investigators have found that both neuroleptic-naive, first-onset schizophrenics, together with chronic sufferers of the illness, consum...

2009-01-01

Empirically defined subtypes of alcohol dependence in an Irish family sample

British Library Electronic Table of Contents (United Kingdom)

Alcohol dependence (AD) is clinically and etiologically heterogeneous. The goal of this study was to explore AD subtypes among a sample of 1221 participants in the Irish Affected Sib Pair Study of Alcohol Dependence, all of whom met DSM-IV criteria for AD. Variables used to identify the subtypes included major depressive disorder, antisocial personality disorder, illicit drug dependence (cannabis, sedatives, stimulants, cocaine, opioids, and hallucinogens), nicotine dependence, the personality traits of neuroticism and novelty seeking, and early alcohol use. Using latent class analysis, a 3-class solution was identified as the most parsimonious description of the data. Individuals in a Mild class were least likely to have comorbid psychopathology, whereas a severe class had highest probabi...

2010-01-01

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

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.

Design, synthesis and evaluation of redox radiopharmaceuticals: a potential new approach for the development of brain imaging agents

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

Benzyl carbamyl analogue of lignocaine: vasodepressor mechanism of action.

The fabrication and complete evaluation are described of a dihydropyridine in equilibrium pyridinium salt type redox system for the delivery of radioiodinated agents to the brain. The pivotal intermediate, N-succinimidyl (1-methylpyridinium iodide)-3-carboxylate was prepared by condensation of nicotinic acid and N-hydroxysuccinimide in the presence of dicyclohexylcarbodimide, followed by quaternization of III with methyl iodide. Tissue distribution studies of "1"2"5I-labeled 4-iodoaniline and the redox agents were performed in rats. ["1"2"5I]Iodoaniline initially showed moderate (0.58% dose/gm) brain uptake with subsequent release of the radioactivity from the brain. ["1"2"5I]Iodoaniline, when coupled to a dihydropyridine carrier showed higher uptake and retention in the brain. The ["1"2"5I]iodophenylethyl analogue showed uptake and retention in the brain to be very similar. Apparently the lipophilic agents cross the blood-brain barrier and are oxidized ...

Structures and luminescent properties of new uranyl-based hybrid materials

1. The benzyl carbamyl analogue of lignocaine [2-(diethylaminoacetamido)-3-carbamyl-4-methyl-5-benzylpyrrole] at an intravenous dose of 4 mg/kg caused a blood pressure decrease of 54 mmHg. 2. A greater hypotensive effect was observed in hypertensive compared to normotensive animals. Anaesthesia magnified the vasodepressor effect in both groups. 3. The analogue did not possess centrally-mediated effects on blood pressure but exerted its hypotensive effect via a peripheral mechanism. 4. The analogue produced a relaxant effect on intestinal and vascular smooth muscle while exerting minimal effects on muscarinic, sympathetic, or ganglionic nicotinic receptors. 5. The analogue exhibited less cardiac depressant action on left ventricular rate (dp/dt) and force of contraction than lignocaine. 6. Lethal effects for the analogue were first observed at 16 mg/kg following intravenous administration and at 500 mg/kg following intraperitoneal administration. 7. In conclusion, ...

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

Six uranyl coordination compounds, UO_2(OH)(PYCA) (1), UO_2(PYCA)_2(H_2O).2H_2O (2), UO_2(PIC)_2 (3), UO_2(H_2O)_2(NIC)_2 (4), UO_2(OH)(HINIC)(INIC) (5), and UO_2(PYTAC)_2(H_2O)_2 (6) were grown as single crystals via hydrothermal synthesis (PYCA - pyrazine-2-carboxylate, PIC - picolinate, NIC - nicotinate, INIC - iso-nicotinate, and PYTAC - 2-(pyridin-4-yl)thiazole-5-carboxylate) to study their optical properties. All six compounds have been identified via single crystal X-ray diffraction and fully characterized via powder X-ray diffraction, infrared spectroscopy, UV-Vis spectroscopy, and fluorescence spectroscopy. Three of the complexes, 1, 3, and 6, represent new structures, and their synthesis and structural characterization is detailed within. The structures of 2, 4, and 5 have previously been reported in the literature. Coordination polymer 1 crystallizes in the orthorhombic space group Pca21 (a = 13.5476(5) Angstroms, b = 6.6047(2) ...

2011-06-01

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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

Production of atomic negative ion beams of the Group IA elements

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.).

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

A method has been developed which enables the direct sputter generation of atomic negative ion beams of all members of the Group IA elements (Li, Na, K, Rb, and Cs). The method consists of the use of sputter samples formed by pressing mixtures of the carbonates of the Group IA elements and 10% (atomic) Cu, Ag, or other metal powder. The following intensities are typical of those observed from carbonate samples subjected to /approximately/3 KeV cesium ion bombardment: Li/sup -/: greater than or equal to0.5 ..mu..A; Na/sup -/: greater than or equal to0.5 ..mu..A; K/sup -/: greater than or equal to0.5 ..mu..A; Rb/sup -/: greater than or equal to0.5 ..mu..A; Cs/sup -/: greater than or equal to0.2 ..mu..A. 7 refs., 2 figs., 1 tab.

1988-01-01

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

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

Health and social impacts of biomass gasification for household energy in rural China: Assessment from three perspectives and emergent insights from their synthesis

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 ...

Ophidian envenomation strategies and the role of purines.

Solid fuels such as coal, wood, and crop straw supply some fraction of household cooking and heating fuel for more than one billion people in China. As these fuels do not generally combust cleanly in household stoves, their use levies large health and environmental burdens, particularly in rural regions. Production of clean-burning fuels from agricultural residue offers one prospect for mitigating health and social burdens imposed by household use of solid fuels. This dissertation explores the question: how might production of clean-burning household fuels from agricultural residues affect human health and social conditions in rural China? I approach this question from three perspectives. First, a technically plausible but currently unproven village-scale energy technology is explored in a scenario bounded by natural resources and substantiated by engineering specifications, estimates of indoor exposures to air pollution, and epidemiological analyses. This analysis asks at the national ...

2005-01-01

Genetic analysis of carbon isotope discrimination and its relation to yield in a wheat doubled haploid population.

Snake envenomation employs three well integrated strategies: prey immobilization via hypotension, prey immobilization via paralysis, and prey digestion. Purines (adenosine, guanosine and inosine) evidently play a central role in the envenomation strategies of most advanced snakes. Purines constitute the perfect multifunctional toxins, participating simultaneously in all three envenomation strategies. Because they are endogenous regulatory compounds in all vertebrates, it is impossible for any prey organism to develop resistance to them. Purine generation from endogenous precursors in the prey explains the presence of many hitherto unexplained enzyme activities in snake venoms: 5'-nucleotidase, endonucleases (including ribonuclease), phosphodiesterase, ATPase, ADPase, phosphomonoesterase, and NADase. Phospholipases A(2), cytotoxins, myotoxins, and heparinase also participate in purine liberation, in addition to their better known functions. Adenosine contributes to prey immobilization ...

2002-04-01