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Acetylcholine
Kinds of Acetylcholine Terms modified by Acetylcholine Selected AbstractsEndothelin attenuates endothelium-dependent platelet inhibition in manACTA PHYSIOLOGICA, Issue 4 2010R. E. Malmström Abstract Aim:, The vascular endothelium produces several substances, including nitric oxide (NO) and endothelin-1 (ET-1), which participate in the regulation of vascular tone in humans. Both these substances may exert other actions of importance for cardiovascular disease, e.g. effects on vascular smooth muscle cell proliferation and inflammation, and NO inhibits platelet function. Experiments were designed to investigate the effect of ET-1 on endothelium-dependent vasodilatation and attenuation of platelet activation. Methods:, In 25 healthy male subjects (25 ± 1 years), forearm blood flow was measured by venous occlusion plethysmography, and platelet activity was assessed by whole blood flow cytometry (platelet fibrinogen binding and P-selectin expression) in unstimulated and adenosine diphosphate (ADP)-stimulated samples during administration of ET-1, the endothelium-dependent vasodilator acetylcholine and the NO synthase inhibitor l -NMMA. Results:, Acetylcholine increased forearm blood flow and significantly inhibited platelet activation in both unstimulated and ADP-stimulated samples. In samples stimulated with 0.3 ,m ADP, fibrinogen binding decreased from 41 ± 4% to 31 ± 3% (P < 0.01, n = 11) after acetylcholine administration. The vasodilator response to acetylcholine was significantly impaired during infusions of ET-1 and l -NMMA. ET-1 did not affect platelet activity per se, whereas l -NMMA increased platelet P-selectin expression. Both ET-1 and l -NMMA attenuated the acetylcholine-induced inhibition of platelet activity. Conclusions:, Our study indicates that, further to inhibiting endothelium-dependent vasodilatation, ET-1 may also attenuate endothelium-dependent inhibition of platelet activation induced by acetylcholine. An enhanced ET-1 activity, as suggested in endothelial dysfunction, may affect endothelium-dependent platelet modulation and thereby have pathophysiological implications. [source] Modulation of rabbit sinoatrial node activation sequence by acetylcholine and isoproterenol investigated with optical mapping techniqueACTA PHYSIOLOGICA, Issue 4 2009D. V. Abramochkin Abstract Aims:, Changes in the rabbit sinoatrial node (SAN) activation sequence with the cholinergic and adrenergic factors were studied. The correlation between the sinus rhythm rate and the leading pacemaker site shift was determined. The hypothesis concerning the cholinergic suppression of nodal cell excitability as one of the mechanisms associated with pacemaker shift was tested. Methods:, A high-resolution optical mapping technique was used to register beat-to-beat changes in the SAN activation pattern under the influence of the cholinergic and adrenergic factors. Results:, Acetylcholine (10 ,m) and strong intramural parasympathetic nerve stimulation caused a pacemaker shift as well as rhythmic slowing and the formation of an inexcitable region in the central part of SAN. In this region the generation of action potentials was suppressed. The slowing of the sinus rhythm (which exceeded 12.8 ± 3.1% of the rhythm control rate) always accompanied the pacemaker shift. Isoproterenol (10, 100 nm, 1 ,m) and sympathetic postganglionic nerve stimulation also evoked a pacemaker shift but without formation of an inexcitable zone. The acceleration of the sinus rhythm, which exceeded 10.5 ± 1.3% of the control rate of the rhythm, always accompanied the shift. Conclusions:, Both cholinergic and adrenergic factors cause pacemaker shifts in the rabbit SAN. While modest changes in the sinus rhythm do not coincide with the pacemaker shift, greater changes always accompany the shift and may be caused by it, according to one hypothesis. The formation of an inexcitable zone at the place where the leading pacemaker is situated is one of the mechanisms associated with pacemaker shift. [source] Signal-On Electrochemiluminescence Biosensors Based on CdS,Carbon Nanotube Nanocomposite for the Sensitive Detection of Choline and AcetylcholineADVANCED FUNCTIONAL MATERIALS, Issue 9 2009Xiao-Fei Wang Abstract This work describes for the first time signal-on electrochemiluminescence (ECL) enzyme biosensors based on cadmium sulfide nanocrystals (CdS NCs) formed in situ on the surface of multi-walled carbon nanotubes (MWCNTs). The MWCNT,CdS can react with H2O2 to generate strong and stable ECL emission in neutral solution. Compared with pure CdS NCs, the MWCNT,CdS can enhance the ECL intensity by 5.3-fold and move the onset ECL potential more positively for about 400,mV, which reduces H2O2 decomposition at the electrode surface and increases detection sensitivity of H2O2. Furthermore, the ECL intensity is less influenced by the presence of oxygen in solution. Benefiting from these properties, signal-on enzyme-based biosensors are fabricated by cross-linking choline oxidase and/or acetylcholine esterase with glutaraldehyde on MWCNT,CdS modified electrodes for detection of choline and acetylcholine. The resulting ECL biosensors show wide linear ranges from 1.7 to 332,µM and 3.3 to 216,µM with lower detection limit of 0.8 and 1.7,µM for choline and acetylcholine, respectively. The common interferents such as ascorbic acid and uric acid in electrochemical enzyme-based biosensors do not interfere with the ECL detection of choline and acetylcholine. Furthermore, both ECL biosensors possess satisfying reproducibility and acceptable stability. [source] Muscarinic receptor blockade in ventral hippocampus and prelimbic cortex impairs memory for socially transmitted food preferenceHIPPOCAMPUS, Issue 5 2009Anna Carballo-Mįrquez Abstract Acetylcholine is involved in learning and memory and, particularly, in olfactory tasks, but reports on its specific role in consolidation processes are somewhat controversial. The present experiment sought to determine the effects of blocking muscarinic cholinergic receptors in the ventral hippocampus (vHPC) and the prelimbic cortex (PLC) on the consolidation of social transmission of food preference, an odor-guided relational task that depends on such brain areas. Adult male Wistar rats were bilaterally infused with scopolamine (20 ,g/site) immediately after social training and showed impairment, relative to vehicle-injected controls, in the expression of the task measured 24 h after learning. Results indicated that scopolamine in the PLC completely abolished memory, suggesting that muscarinic transmission in this cortical region is crucial for consolidation of recent socially acquired information. Muscarinic receptors in the vHPC contribute in some way to task consolidation, as the rats injected with scopolamine in the vHPC showed significantly lower trained food preference than control rats, but higher than both chance level and that of the PLC-injected rats. Behavioral measures such as social interaction, motivation to eat, neophobia, or exploration did not differ between rats infused with scopolamine or vehicle. Such data suggest a possible differential role of muscarinic receptors in the PLC and the vHPC in the initial consolidation of a naturalistic form of nonspatial relational memory. © 2008 Wiley-Liss, Inc. [source] Translating Electronic Currents to Precise Acetylcholine,Induced Neuronal Signaling Using an Organic Electrophoretic Delivery DeviceADVANCED MATERIALS, Issue 44 2009Klas Tybrandt A miniaturized organic electronic ion pump (OEIP) based on conjugated polymers is developed for delivery of positively charged biomolecules. Characterization shows that applied voltage can precisely modulate the delivery rate of the neurotransmitter acetylcholine. The capability of the device is demonstrated by convection-free, spatiotemporally resolved delivery of acetylcholine via a 10 µm channel for dynamic stimulation of single neuronal cells. [source] Administration of acetylcholine to the spermatic nerve plexus inhibits testosterone secretion in an in vitro isolated rat testis,nerve plexus systemINTERNATIONAL JOURNAL OF ANDROLOGY, Issue 3 2002C. Zhu Strong evidence indicated that spermatic nerves are involved in the regulation of testosterone secretion. Our previous work showed that the inferior spermatic nerves play a more significant role than the superior ones in the regulation of testosterone secretion. However, it is unknown whether traditional neurotransmitters are involved in this regulation. In order to evaluate this point, the present experiments were carried out in an in vitro system where an isolated testis,spermatic nerve plexus preparation was incubated in two separate containers, one for the testis and the other for the nerve plexus and both interconnected by the inferior spermatic nerves. Both tissues were maintained in the same environmental conditions except for the neurotransmitter treatment, applied only to the nerve plexus. Acetylcholine can significantly inhibit the secretion of testosterone until the end of incubation. The present experiments suggest that the secretion of testosterone could be regulated, at least in part, by acetylcholine through the inferior spermatic nerves. [source] Role of Repolarization Restitution in the Development of Coarse and Fine Atrial Fibrillation in the Isolated Canine Right AtriaJOURNAL OF CARDIOVASCULAR ELECTROPHYSIOLOGY, Issue 6 2005ALEXANDER BURASHNIKOV Ph.D. Introduction: Although the role of action potential duration restitution (APD-R) in the initiation and maintenance of ventricular fibrillation (VF) has been the subject of numerous investigations, its role in the generation of atrial fibrillation (AF) is less well studied. The cellular and ionic basis for coarse versus fine AF is not well delineated. Methods and Results: We measured APD-R during acetylcholine-mediated AF as well as during pacing (standard and dynamic protocols) in crista teriminalis, pectinate muscle, superior vena cava, and appendage of isolated canine arterially perfused right atria (n = 15). Transmembrane action potential (TAP), pseudo-ECG, and isometric tension development were simultaneously recorded. Acetylcholine flattened APD-R measured by both standard and dynamic protocols, but promoted induction of AF. AF was initially coarse, converting to fine within 3,15 minutes of AF. Coarse, but not fine AF was associated with dramatic fluctuations in tension development, reflecting wide variations in intracellular calcium activity ([Ca2+]i). During coarse AF, APD-R data displayed a cloud-like distribution pattern, with a wide range of maximum APD-R slope (from 1.21 to 0.35). A maximum APD-R slope >1 was observed only in crista terminalis (3/10). The APD-R relationship was relatively linear and flat during fine AF. Reduction of [Ca2+]i was associated with fine AF whereas augmentation of [Ca2+]i with coarse AF. Conclusions: Our data indicate that while APD-R may have a limited role in the maintenance of coarse AF, it is unlikely to contribute to the maintenance of fine AF and that [Ca2+]i dynamics determine the degree to which AF is coarse or fine. [source] Adrenergic-Cholinergic Interaction that Modulates Repolarization in the Atrium is Altered with AgingJOURNAL OF CARDIOVASCULAR ELECTROPHYSIOLOGY, Issue 4 2002EUGENE A. SOSUNOV Ph.D. Autonomic Modulation of Atrial Repolarization.Introduction: Aging is associated with involution of both limbs of the autonomic nervous system, and the prejunctional and postjunctional effects of adrenergic and cholinergic stimulation are altered with senescence. Hence, postjunctional age-related changes in adrenergic-cholinergic interaction are a likely occurrence and may contribute to an altered substrate for arrhythmias. Methods and Results: Microelectrode techniques were used to record action potentials from epicardial slices of Bachmann's bundles of dogs aged 3 to 5 years (adult) and 8 to 12 years (old) in the absence or presence of acetylcholine and isoproterenol (separately and in combination). In control, action potential duration to 90% repolarization (APD) was longer in old atria. Acetylcholine (10,8 to 10,5 mol/L) in a concentration-dependent manner hyperpolarized and shortened APD in both tissues, with more prominent effects in the old. The effects of isoproterenol (10,9 to 10,6 mol/L) to elevate the plateau and shorten APD were about the same in both adult and old tissues. In adults, low concentrations of isoproterenol (10,9 and 10,8 mol/L) significantly prolonged APD, which had been first shortened by acetylcholine. This effect of isoproterenol was decreased in old atrial tissue, resulting in shorter APD in old than adult atria in the combined presence of beta-adrenergic and muscarinic agonists. Conclusion: In adult Bachmann's bundle, beta-adrenergic stimulation effectively operates as a "brake" to decrease the extent of cholinergic-induced APD shortening. The action of beta-adrenergic stimulation to antagonize acetylcholine-induced acceleration of repolarization declines with age, which may contribute to an altered arrhythmogenic substrate. [source] Acetylcholine and Alcohol Sensitivity of Neuronal Nicotinic Acetylcholine Receptors: Mutations in Transmembrane DomainsALCOHOLISM, Issue 12 2002Cecilia M. Borghese Background The effect of n-alcohols on glycine and ,-aminobutyric acid type A receptors depends on two specific amino acids (AAs) located in the transmembrane domains (TM) 2 and 3. Our aim was to assess whether the corresponding AAs in the neuronal nicotinic acetylcholine receptor (nAChR) also formed a binding pocket for alcohols. Methods We made single AA substitutions in the homologous sites in rat neuronal nAChR ,2 and ,4 (,L261 and ,L283) and expressed them in Xenopus laevis oocytes in combination with ,4 wild type. The effect of different n-alcohols was studied in ,4(L261A),4 and ,4(L283A),4 nAChRs. The effect of ethanol, propanol, and octanol on acetylcholine (ACh) responses was studied in ,2(L261X),4 and ,2(L283X),4 nAChRs. Results Most of the mutations in the ,2 subunit, in either the 261 or the 283 position, induced changes in ACh sensitivity and increased alcohol action, but none was able to reduce ethanol potentiation. In ,4(L283A),4, enhancement of potentiation by short-chain alcohols was observed, as well as a change from inhibition to potentiation for long-chain alcohols. The exposure of the AAs was assessed through the action of a charged thiol-specific reagent on ,2(L261C),4 and ,2(L283C),4, and these experiments suggest that the AA in TM2 is located in a water-accessible position, whereas the AA in TM3 is inaccessible. However, a noncharged thiol-specific reagent did not affect either ACh responses or ethanol effect on ,2(L261C),4. Conclusions The AAs located at positions 261 and 283 of the ,2 and ,4 nAChR subunits do not seem to form a binding pocket for alcohols. Additional studies are required to determine whether alcohols act on a site near these AAs or on sites unrelated to the TM2-TM3 site found in glycine and ,-aminobutyric acid type A receptors. [source] Inhibition of NAD(P)H Oxidase Alleviates Impaired NOS-dependent Responses of Pial Arterioles in Type 1 Diabetes MellitusMICROCIRCULATION, Issue 7 2006WILLIAM G. MAYHAN ABSTRACT Objective: The goal was to identify the role of NAD(P)H oxidase in cerebrovascular dysfunction in type 1 diabetes mellitus (T1D). Methods: In a first series of studies, rats were assigned to nondiabetic, diabetic (streptozotocin; 50 mg/kg IP), nondiabetic-apocynin (40 mg/kg/day in drinking water)-treated and diabetic-apocynin-treated groups. Two to three months later, the authors examined in vivo responses of pial arterioles to nitric oxide synthase (NOS)-dependent (acetylcholine and adenosine diphosphate (ADP)) and -independent (nitroglycerin) agonists. Next, they used Western blot analysis to examine protein levels for subunits of NAD(P)H oxidase in cerebral microvessels and parietal cortex tissue of nondiabetic and diabetic rats. Finally, they measured superoxide production by parietal cortex tissue in nondiabetic and diabetic rats. Results: Acetylcholine- and ADP-induced dilatation of pial arterioles was impaired in diabetic compared to nondiabetic rats. In addition, while apocynin did not alter responses in nondiabetic rats, apocynin alleviated T1D-induced impairment of NOS-dependent vasodilatation. In addition, p47phox and gp91phox proteins were elevated in cerebral microvessels and parietal cortex tissue, respectively, of diabetic compared to nondiabetic rats. Further, basal production of superoxide was increased in diabetic compared to nondiabetic rats and apocynin decreased this basal production. Conclusions: The findings suggest that T1D impairs NOS-dependent reactivity of cerebral arterioles by a mechanism related to the formation of superoxide via activation of NAD(P)H oxidase. [source] Acetylcholine-Induced Vasodilation and Reactive Hyperemia Are Not Affected by Acute Cyclo-Oxygenase Inhibition in Human SkinMICROCIRCULATION, Issue 4 2004Anne Dalle-Ave Objective: To examine whether prostaglandins are involved in endothelium-dependent vasodilatory responses of the skin microcirculation. Methods: Twenty-three young male volunteers were studied on 2 different days 1,3 weeks apart. On each experimental day the forearm skin blood flow response to iontophoretically applied acetylcholine (Ach, an endothelium-dependent vasodilator) was determined with laser Doppler imaging following the intravenous administration of either the cyclo-oxygenase inhibitor lysine acetylsalicylate (L-AS), 900 mg, or the oral intake of indomethacin, 75 mg. Acetylcholine was iontophoresed both in presence and in absence of surface anesthesia. In some subjects, the effects of L-AS on skin reactive hyperemia were also assessed. Results: Acute cyclo-oxygenase inhibition with either drug influenced neither the skin blood flow response to 4 different doses of Ach (0.28, 1.4, 7, and 14 mC/cm2) nor reactive hyperemia. The peak vasodilatory response to Ach was significantly increased by skin anesthesia, regardless of whether the subjects received the cyclo-oxygenase inhibitor or not. For example, the mean response (± SD) to the largest dose of Ach (tested in 6 subjects, expressed in perfusion units) were as follows: in absence of anesthesia: L-AS 339 ± 105, placebo 344 ± 68; with anesthesia: L-AS 453 ± 76, placebo 452 ± 65 (p < .01 for effect of anesthesia). Conclusions: These data give no support for a contribution of prostaglandins to acetylcholine-induced vasodilation or to reactive hyperemia in the skin microcirculation. In this vascular bed, local anesthesia seems to amplify acetylcholine-induced vasodilation via a prostaglandin-independent mechanism. [source] Neurotransmitters and neuropeptides in the brain of the locustMICROSCOPY RESEARCH AND TECHNIQUE, Issue 3 2002Uwe Homberg Abstract As part of continuous research on the neurobiology of the locust, the distribution and functions of neurotransmitter candidates in the nervous system have been analyzed particularly well. In the locust brain, acetylcholine, glutamate, ,-aminobutyric acid (GABA), and the biogenic amines serotonin, dopamine, octopamine, and histamine most likely serve a transmitter function. Increasing evidence, furthermore, supports a signalling function for the gaseous molecule nitric oxide, but a role for neuroptides is so far suggested only by immunocytochemistry. Acetylcholine, glutamate, and GABA appear to be present in large numbers of interneurons. As in other insects, antennal sensory afferents might be cholinergic, while glutamate is the transmitter candidate of antennal motoneurons. GABA is regarded as the principle inhibitory transmitter of the brain, which is supported by physiological studies in the antennal lobe. The cellular distribution of biogenic amines has been analyzed particularly well, in some cases down to physiologically characterized neurons. Amines are present in small numbers of interneurons, often with large branching patterns, suggesting neuromodulatory roles. Histamine, furthermore, is the transmitter of photoreceptor neurons. In addition to these "classical transmitter substances," more than 60 neuropeptides were identified in the locust. Many antisera against locust neuropeptides label characteristic patterns of neurosecretory neurons and interneurons, suggesting that these peptides have neuroactive functions in addition to hormonal roles. Physiological studies supporting a neuroactive role, however, are still lacking. Nitric oxide, the latest addition to the list of neurotransmitter candidates, appears to be involved in early stages of sensory processing in the visual and olfactory systems. Microsc. Res. Tech. 56:189,209, 2002. © 2002 Wiley-Liss, Inc. [source] Effect of a dysmenorrhea Chinese medicinal prescription on uterus contractility in vitroPHYTOTHERAPY RESEARCH, Issue 7 2003Chun-Sen Hsu Abstract Dysmenorrhea is a common gynecologic complaint. After their ,rst menstrual period, 30%,60% of American women suffer from some level of discomfort. It is estimated that 6 billion work hours are lost in this manner every year in the United States which equals an economic loss of nearly US$200 million. Dysmenorrhea is not only a problem for women but also one which affects quality of life and even reduces productivity in general. Dysmenorrhea is directly related to elevated levels of PGF2, (prostaglandins F2,) and is treated using nonsteroid anti-in,ammatory drugs in Western medicine. Though ef,cacy of the latter is rapid, there are many side effects to the liver, kidney, and digestive system. The anti-in,ammatory effect is temporary, and such drugs are unable to provide a long-term cure. Because of this, Chinese medicinal therapy is being considered as a feasible alternative medicine. In this study, Wen-Jing Tang (one of the dysmenorrhea Chinese medicinal prescriptions) was selected. A 50% alcoholic solution was used to extract active ingredients and create a freeze-dried product. At ,rst, Wen-Jing Tang was used to suppress spontaneous contractions and prostaglandins F2, -induced contractions of rat uterine smooth muscle in vitro. Then, an assessment was performed to determine the mechanism of the prescription. Acetylcholine, ergonovine, propranolol, oxytocin, and KCl were used to analyze the physiological mechanisms of WJT. The results show that antagonism of both PGF2, and ACh are the major mechanisms for treating dysmenorrhea by Wen-Jing Tang. Furthermore, the antagonistic effect of KCl-depolarization contractions may be an auxiliary mechanism of the curative effect. Copyright © 2003 John Wiley & Sons, Ltd. [source] Smooth muscle contraction induced by Indigofera dendroides leaf extracts may involve calcium mobilization via potential sensitive channelsPHYTOTHERAPY RESEARCH, Issue 7 2003S. Amos Abstract The contractile effects of the aqueous extract of the leaves of Indigofera dendroides (ID) were studied on the gastrointestinal motility in mice and isolated smooth muscle preparations obtained from rats and guinea pigs. The contractile effects of 10,6 M acetylcholine, 80 mM KCl and 1.6 mg/ml ID were measured on the rat ileal smooth muscle exposed to calcium-free buffer or physiological solution, to determine the calcium pools mobilized by extract for activation of contraction. Acute toxicity test (LD50) was also carried out in mice. The result showed that ID (0.05,3.2 mg/ml) produced a concentration-dependent contraction of the guinea pig and rat ileum. These responses were not blocked by mepyramine (2.49 × 10,9 M), verapamil (8.14 × 10,9 M), or pirenzepine (4.7 × 10,7 M), but were blocked completely by atropine (2.92 × 10,9 M). A signi.cant increase in propulsion of gastrointestinal motility was observed. Acetylcholine, KCl and ID produced contractions in Ca2+ free media. The phasic components of the contractile responses to Ach as well as the tonic component of K+ and ID-induced contractions were relatively resistant to short periods of calcium-free exposure. Ach, K+ and ID still caused contractions in the presence of verapamil. The data revealed that ID-induced contractions were not mediated by histaminergic receptors, calcium channels, M1 muscarinic receptors. It also suggests that Ach mobilize Ca from some tightly bound or intracellular pool, whereas high K+ and ID may mobilize Ca from some superficial or loosely-bound pool. Copyright © 2003 John Wiley & Sons, Ltd. [source] The neurochemistry of waking and sleeping mental activity: The disinhibition-dopamine hypothesisPSYCHIATRY AND CLINICAL NEUROSCIENCES, Issue 4 2002CLAUDE GOTTESMANN Abstract This paper describes a hypothesis related to the neurochemical background of sleep-waking mental activity which, although associated with subcortical structures, is principally generated in the cerebral cortex. Acetylcholine, which mainly activates cortical neurons, is released at the maximal rate during waking and rapid eye movement (REM) sleep dreaming stage. Its importance in mental functioning is well-known. However, brainstem-generated monoamines, which mainly inhibit cortical neurons, are released during waking. Both kinds of influences contribute to the organized mentation of waking. During slow wave sleep, these two types of influence decrease in intensity but maintain a sufficiently high level to allow mental activity involving fairly abstract pseudo-thoughts, a mode of activity modelled on the diurnal pattern of which it is a poor reply. During REM sleep, the monoaminergic neurons become silent except for the dopaminergic ones. This results in a large disinhibition and the maintained dopamine influence may be involved in the familiar psychotic-like mental activity of dreaming. Indeed, in this original activation,disinhibition state, the increase of dopamine influence at the prefrontal cortex level could explain the almost total absence of negative symptoms of schizophrenia during dreaming, while an increase in the nucleus accumbens is possibly responsible for hallucinations and delusions, which are regular features of mentation during this sleep stage. [source] Quantification of acetylcholine, an essential neurotransmitter, in brain microdialysis samples by liquid chromatography mass spectrometryBIOMEDICAL CHROMATOGRAPHY, Issue 1 2010Ramakrishna Nirogi Abstract Chemical neurotransmission has been the subject of intensive investigations in recent years. Acetylcholine is an essential neurotransmitter in the central nervous system as it has an effect on alertness, memory and learning. Enzymatic hydrolysis of acetylcholine in the synaptic cleft is fast and quickly metabolizes to choline and acetate by acetylcholinesterase. Hence the concentration in the extracellular fluid of the brain is low (0.1,6,nm). Techniques such as microdialysis are routinely employed to measure acetylcholine levels in living brain systems and the microdialysis sample volumes are usually less than 50,µL. In order to develop medicine for the diseases associated with cognitive dysfunction like mild cognitive impairment, Alzheimer's disease, schizophrenia and Parkinson's disease, or to study the mechanism of the illness, it is important to measure the concentration of acetylcholine in the extracellular fluid of the brain. Recently considerable attention has been focused on the development of chromatographic,mass spectrometric techniques to provide more sensitive and accurate quantification of acetylcholine collected from in-vivo brain microdialysis experiments. This review will provide a brief overview of acetylcholine biosynthesis, microdialysis technique and liquid chromatography mass spectrometry, which is being used to quantitate extracellular levels of acetylcholine. Copyright © 2009 John Wiley & Sons, Ltd. [source] Solvent-Free Synthesis of Arylamides and Arylimides, Analogues of Acetylcholine.CHEMINFORM, Issue 50 2005J. Trujillo-Ferrara Abstract For Abstract see ChemInform Abstract in Full Text. [source] Four Generations of Water-Soluble Dendrimers with 9 to 243 Benzoate Tethers: Synthesis and Dendritic Effects on Their Ion Pairing with Acetylcholine, Benzyltriethylammonium, and Dopamine in WaterCHEMISTRY - A EUROPEAN JOURNAL, Issue 18 2008Elodie Boisselier Abstract Water-soluble benzoate-terminated dendrimers of four generations (from G0 with 9 branches to G3 with 243 branches) were synthesized and fully characterized. They form water-soluble assemblies by ion-pairing interactions with three cations of medicinal interest (acetylcoline, benzyltriethylammonium, and dopamine), which were characterized and investigated by 1H,NMR spectroscopy, whereas such interactions do not provoke any significant shift of 1H,NMR signals with the monomeric benzoate anion. The calculated association constants confirm that the dendritic carboxylate termini reversibly form ion pairs and aggregates. Diffusion coefficients and hydrodynamic diameters of the dendrimers, as well as changes thereof on interaction with the cations, were evaluated by DOSY experiments. The lack of increase of dendrimer size on addition of the cations and the upfield shifts of the 1H,NMR signals of the cation indicate encapsulation within the hydrophobic dendrimer interiors together with probable backfolding of the benzoate termini. [source] Atrial Tachyarrhythmias Induced By Acetylcholine In Tilapia (Oreochromis SP.) Isolated AtriaCLINICAL AND EXPERIMENTAL PHARMACOLOGY AND PHYSIOLOGY, Issue 5-6 2000Tsai-Chu Lin SUMMARY 1. Effects of the parasympathetic neuromediator acetylcholine (ACh) on atrial tissues vary greatly depending on the species, the type of atrial cells and experimental conditions. The aim of the present study was to investigate, with microelectrode techniques, the arrhythmogenic effects of ACh in tilapia (Oreochromis sp.) isolated atria at room (22,25°C) and high temperature (37°C). 2. Acetylcholine (1,10 ,mol/L) shortened action potential duration (APD), depressed action potential plateau and decreased twitch force in tilapia atria, as it did in human atrial fibres. In addition, ACh induced premature responses and re-entrant tachyarrhythmias (TA; frequency range from 7 to 25 Hz) in five of 19 and 14 of 22 tilapia atria tested at room and high temperature, respectively. The higher incidence of ACh-induced TA at 37°C compared with room temperature was statistically significant. 3. The ACh-induced TA consisted of high-frequency and uniform action potentials accompanied by tension oscillation and elevation of diastolic force (flutter). Acetylcholine-induced TA could be readily abolished by atropine (1 ,mol/L) and prevented by treatment with agents with local anaesthetic properties, such as 0.1 ,mol/L tetrodotoxin or 3 ,mol/L quinidine. The antagonistic action of quinidine occurred without significant prolongation of APD. 4. The present findings suggest that pharmacological concentrations of the cholinergic muscarinic agonist ACh readily induce TA (mainly atrial flutter) in tilapia atria, presumably via sodium channel-dependent re-entrant excitation. The poikilothermic tilapia appears to be an appropriate animal model for the study of atrial TA. [source] Acetylcholine- and ergonovine-induced coronary microvascular spasm reflected by increased coronary vascular resistance and myocardial lactate productionCLINICAL CARDIOLOGY, Issue 3 2000Masashi Horimoto M.D. Abstract Diagnosis of coronary microvascular spasm remains largely speculative because it has been mostly based on chest pain and electrocardiographic ST-segment shift with slow filling of contrast medium into the coronary artery. A patient with resting chest pain and normal coronary angiograms underwent provocative tests with intracoronary acetylcholine (ACh) and ergonovine. During the tests, coronary diameter and flow velocity in the left anterior descending (LAD) coronary artery were measured with quantitative coronary angiography and intracoronary Doppler guide wire, respectively. Vascular resistance of the LAD and lactate production were determined separately. With injections of 100 ,g of ACh and 20 ,g of ergonovine, chest pain occurred with ST-segment elevation in the precordial leads in the absence of epicardial coronary spasm. Coronary vascular resistance increased by 2.2- and 1.6-fold of the baseline value with ACh and ergonovine, respectively. Myocardial lactate production was noted during the ST-segment elevation. Coronary microvascular spasm was verified by the increment in coronary vascular resistance and myocardial lactate production with concomitant ST-segment elevation in the presence of normal coronary angiograms. [source] Adenosine A1 receptors and vascular reactivityACTA PHYSIOLOGICA, Issue 2 2010Y. Wang Abstract Aim:, Blood pressure is higher in A1 receptor knock-out (A1R,/,) mice than in wild type litter mates (A1R+/+) and we have examined if this could be related to altered vascular functions. Methods:, Contraction of aortic rings and mesenteric arteries were examined. To examine if the adenosine A1 receptor-mediated contraction of aortic muscle was functionally important we examined pulse pressure (PP) and augmentation index (AIX) using a sensor that allows measurements of rapid pressure transients. Results:, Contraction of aortic rings to phenylephrine and relaxation to acetylcholine were similar between genotypes. The non-selective adenosine receptor agonist N -ethyl carboxamido adenosine (NECA) enhanced the contractile response, and this was eliminated in aortas from A1R,/, mice. However, in mesenteric arteries no contractile response was seen and adenosine-mediated relaxation was identical between studied genotypes. A2B adenosine receptors, rather than A2A receptors, may be mainly responsible for the vasorelaxation induced by adenosine analogues in the examined mouse vessels. PP was higher in A1R,/, mice, but variability was unaltered. AIX was not different between genotypes, but the NECA-induced fall was larger in A1R,/, mice. Conclusions:, The role of adenosine A1 receptors in regulating vessel tone differs between blood vessels. Furthermore, contractile effects on isolated vessels cannot explain the blood pressure in A1 knock-out mice. The A1 receptor modulation of blood pressure is therefore mainly related to extravascular factors. [source] Endothelin attenuates endothelium-dependent platelet inhibition in manACTA PHYSIOLOGICA, Issue 4 2010R. E. Malmström Abstract Aim:, The vascular endothelium produces several substances, including nitric oxide (NO) and endothelin-1 (ET-1), which participate in the regulation of vascular tone in humans. Both these substances may exert other actions of importance for cardiovascular disease, e.g. effects on vascular smooth muscle cell proliferation and inflammation, and NO inhibits platelet function. Experiments were designed to investigate the effect of ET-1 on endothelium-dependent vasodilatation and attenuation of platelet activation. Methods:, In 25 healthy male subjects (25 ± 1 years), forearm blood flow was measured by venous occlusion plethysmography, and platelet activity was assessed by whole blood flow cytometry (platelet fibrinogen binding and P-selectin expression) in unstimulated and adenosine diphosphate (ADP)-stimulated samples during administration of ET-1, the endothelium-dependent vasodilator acetylcholine and the NO synthase inhibitor l -NMMA. Results:, Acetylcholine increased forearm blood flow and significantly inhibited platelet activation in both unstimulated and ADP-stimulated samples. In samples stimulated with 0.3 ,m ADP, fibrinogen binding decreased from 41 ± 4% to 31 ± 3% (P < 0.01, n = 11) after acetylcholine administration. The vasodilator response to acetylcholine was significantly impaired during infusions of ET-1 and l -NMMA. ET-1 did not affect platelet activity per se, whereas l -NMMA increased platelet P-selectin expression. Both ET-1 and l -NMMA attenuated the acetylcholine-induced inhibition of platelet activity. Conclusions:, Our study indicates that, further to inhibiting endothelium-dependent vasodilatation, ET-1 may also attenuate endothelium-dependent inhibition of platelet activation induced by acetylcholine. An enhanced ET-1 activity, as suggested in endothelial dysfunction, may affect endothelium-dependent platelet modulation and thereby have pathophysiological implications. [source] Activation of the basal forebrain by the orexin/hypocretin neuronesACTA PHYSIOLOGICA, Issue 3 2010E. Arrigoni Abstract The orexin neurones play an essential role in driving arousal and in maintaining normal wakefulness. Lack of orexin neurotransmission produces a chronic state of hypoarousal characterized by excessive sleepiness, frequent transitions between wake and sleep, and episodes of cataplexy. A growing body of research now suggests that the basal forebrain (BF) may be a key site through which the orexin-producing neurones promote arousal. Here we review anatomical, pharmacological and electrophysiological studies on how the orexin neurones may promote arousal by exciting cortically projecting neurones of the BF. Orexin fibres synapse on BF cholinergic neurones and orexin-A is released in the BF during waking. Local application of orexins excites BF cholinergic neurones, induces cortical release of acetylcholine and promotes wakefulness. The orexin neurones also contain and probably co-release the inhibitory neuropeptide dynorphin. We found that orexin-A and dynorphin have specific effects on different classes of BF neurones that project to the cortex. Cholinergic neurones were directly excited by orexin-A, but did not respond to dynorphin. Non-cholinergic BF neurones that project to the cortex seem to comprise at least two populations with some directly excited by orexin-A that may represent wake-active, GABAergic neurones, whereas others did not respond to orexin-A but were inhibited by dynorphin and may be sleep-active, GABAergic neurones. This evidence suggests that the BF is a key site through which orexins activate the cortex and promote behavioural arousal. In addition, orexins and dynorphin may act synergistically in the BF to promote arousal and improve cognitive performance. [source] Enhanced pulmonary expression of the TrkB neurotrophin receptor in hypoxic rats is associated with increased acetylcholine-induced airway contractilityACTA PHYSIOLOGICA, Issue 3 2009L. K. Sciesielski Abstract Aim:, We have recently reported that hypoxia stimulates transcription of the TrkB neurotrophin receptor in cultured cells via stabilization of hypoxia-inducible factor-1,. Here we investigated whether the expression of TrkB and other neurotrophin receptors is oxygen-sensitive also in vivo, and explored the functional consequences of an oxygen-regulated TrkB expression. Methods:, Rats were exposed either to 21% O2 or 8% O2 for 6 h and TrkB was analysed by reverse transcription real-time PCR, in situ mRNA hybridization, and immunological techniques. The importance of the brain-derived neurotrophic factor (BDNF)-TrkB pathway in the control of mechanical airway function was assessed on isolated tracheal segments from normoxic and hypoxic rats. Results:,TrkB transcripts were increased approx. 15-fold in the lungs of hypoxic rats, and the respiratory epithelium was identified as the site of enhanced TrkB expression in hypoxia. The TrkB ligand, BDNF, significantly increased the contractile response to acetylcholine (ACh) of isolated tracheal segments from hypoxic but not from normoxic rats. This effect of BDNF was prevented by pre-incubation of the tissue specimens with the tyrosine kinase inhibitor K252a and by mechanical removal of the TrkB containing airway epithelium. Likewise, the nitric oxide (NO) synthase inhibitor l -NAME abrogated the influence of BDNF on ACh-induced contractions of isolated tracheal segments from hypoxic rats. Conclusion:, These results demonstrate that systemic hypoxia stimulates expression of the TrkB neurotrophin receptor in the airway epithelium. Furthermore, activation of TrkB signalling by BDNF in hypoxia enhances mechanical airway contractility to ACh through a mechanism that requires NO. [source] Modulation of rabbit sinoatrial node activation sequence by acetylcholine and isoproterenol investigated with optical mapping techniqueACTA PHYSIOLOGICA, Issue 4 2009D. V. Abramochkin Abstract Aims:, Changes in the rabbit sinoatrial node (SAN) activation sequence with the cholinergic and adrenergic factors were studied. The correlation between the sinus rhythm rate and the leading pacemaker site shift was determined. The hypothesis concerning the cholinergic suppression of nodal cell excitability as one of the mechanisms associated with pacemaker shift was tested. Methods:, A high-resolution optical mapping technique was used to register beat-to-beat changes in the SAN activation pattern under the influence of the cholinergic and adrenergic factors. Results:, Acetylcholine (10 ,m) and strong intramural parasympathetic nerve stimulation caused a pacemaker shift as well as rhythmic slowing and the formation of an inexcitable region in the central part of SAN. In this region the generation of action potentials was suppressed. The slowing of the sinus rhythm (which exceeded 12.8 ± 3.1% of the rhythm control rate) always accompanied the pacemaker shift. Isoproterenol (10, 100 nm, 1 ,m) and sympathetic postganglionic nerve stimulation also evoked a pacemaker shift but without formation of an inexcitable zone. The acceleration of the sinus rhythm, which exceeded 10.5 ± 1.3% of the control rate of the rhythm, always accompanied the shift. Conclusions:, Both cholinergic and adrenergic factors cause pacemaker shifts in the rabbit SAN. While modest changes in the sinus rhythm do not coincide with the pacemaker shift, greater changes always accompany the shift and may be caused by it, according to one hypothesis. The formation of an inexcitable zone at the place where the leading pacemaker is situated is one of the mechanisms associated with pacemaker shift. [source] Exposure of rats to hyperoxia enhances relaxation of isolated aortic rings and reduces infarct size of isolated heartsACTA PHYSIOLOGICA, Issue 4 2002P. Tähepõld ABSTRACT Exposure of rats to hyperoxia before organ harvesting protected their isolated hearts against global ischaemia,reperfusion injury in a previous study. The present study investigates whether hyperoxia influences vasomotor function and regional ischaemia of the heart. Isolated rings of the thoracic aorta were obtained from rats immediately or 24 h after in vivo exposure to 60 min of hyperoxia (>95% O2), and the in vitro dose,response to phenylephrine (PHE), prostaglandin F2, (PGF2,) and endothelin-1 (ET-1), acetylcholine (Ach) and sodium nitroprusside (SNP) was assessed. Hyperoxia in vivo increased the relaxation of aortic rings to Ach and SNP, while it delayed contraction to PHE. The effect was more evident when the vessels were harvested immediately rather than 24 h after hyperoxic exposure. In separate experiments rat hearts were isolated immediately after hyperoxia, buffer-perfused, and subjected to 30 min of regional ischaemia and reperfused for 120 min. Infarct size was determined by triphenyl tetrazolium chloride staining. Hyperoxia significantly reduced infarct size. In normoxic controls 23.0 ± 8.3% of the area at risk was infarcted, while in hyperoxic animals infarct size was 14.8 ± 5.6% of the area at risk (P = 0.012). Exposure of rats to hyperoxia modifies the vasomotor response of isolated aortic rings, and reduces the infarct size of isolated rat heart. These novel aspects of hyperoxic treatment require further studies to explore the potential of its clinical application. [source] Effects of right and left vagal stimulation on left ventricular acetylcholine levels in the catACTA PHYSIOLOGICA, Issue 1 2001T. Akiyama To test the effectiveness of, and the interactions between, right and left vagal stimulation on left ventricular acetylcholine (ACh) levels, we applied the dialysis technique to the heart of anaesthetized cats. Dialysis probes were implanted in the left ventricular myocardium and perfused with Krebs,Henseleit buffer containing eserine. Dialysate ACh content was measured as an index of ACh release from post-ganglionic vagal nerve terminals in the left ventricular myocardium. We electrically stimulated the right and left cervical vagal nerves separately or together and investigated the dialysate ACh response. In two different regions of the left ventricle, substantial dialysate ACh responses were observed by the stimulation (20 Hz) of both right and left cervical vagal nerves. At stimulation frequencies of both 10 and 20 Hz, the dialysate ACh response to the bilateral vagal stimulation was almost algebraically the calculated sum of the individual dialysate ACh responses to unilateral vagal stimulation. In conclusion, ACh levels in the left ventricle are affected by both right and left vagal nerves and show little evidence of interactions between right and left vagal nerves at the level of the cardiac ganglia. [source] Activity of nAChRs containing ,9 subunits modulates synapse stabilization via bidirectional signaling programsDEVELOPMENTAL NEUROBIOLOGY, Issue 14 2009Vidya Murthy Abstract Although the synaptogenic program for cholinergic synapses of the neuromuscular junction is well known, little is known of the identity or dynamic expression patterns of proteins involved in non-neuromuscular nicotinic synapse development. We have previously demonstrated abnormal presynaptic terminal morphology following loss of nicotinic acetylcholine receptor (nAChR) ,9 subunit expression in adult cochleae. However, the molecular mechanisms underlying these changes have remained obscure. To better understand synapse formation and the role of cholinergic activity in the synaptogenesis of the inner ear, we exploit the nAChR ,9 subunit null mouse. In this mouse, functional acetylcholine (ACh) neurotransmission to the hair cells is completely silenced. Results demonstrate a premature, effusive innervation to the synaptic pole of the outer hair cells in ,9 null mice coinciding with delayed expression of cell adhesion proteins during the period of effusive contact. Collapse of the ectopic innervation coincides with an age-related hyperexpression pattern in the null mice. In addition, we document changes in expression of presynaptic vesicle recycling/trafficking machinery in the ,9 null mice that suggests a bidirectional information flow between the target of the neural innervation (the hair cells) and the presynaptic terminal that is modified by hair cell nAChR activity. Loss of nAChR activity may alter transcriptional activity, as CREB binding protein expression is decreased coincident with the increased expression of N-Cadherin in the adult ,9 null mice. Finally, by using mice expressing the nondesensitizing ,9 L9,T point mutant nAChR subunit, we show that increased nAChR activity drives synaptic hyperinnervation. © 2009 Wiley Periodicals, Inc. Develop Neurobiol, 2009 [source] Dopamine modulation of the In vivo acetylcholine response in the Drosophila mushroom bodyDEVELOPMENTAL NEUROBIOLOGY, Issue 11 2009Vitold Tsydzik Abstract Olfactory sensory information in Drosophila is transmitted through antennal lobe projections to Mushroom Body neurons (Kenyon cells) by means of cholinergic synapses. Application of acetylcholine (ACh) and odors produce significant increases in intracellular calcium ([Ca2+]i) in these neurons. Behavioral studies show that Kenyon cell activity is modulated by dopaminergic inputs and this modulation is thought to be the basis for an olfactory conditioned response. However, quantitative assessment of the synaptic inputs to Kenyon cells is currently lacking. To assess neuronal activity under in vivo conditions, we have used the endogenously-expressed camgaroo reporter to measure [Ca2+]i in these neurons. We report here the dose-response relationship of Kenyon cells for ACh and dopamine (DA). Importantly, we also show that simultaneous application of ACh and DA results in a significant decrease in the response to ACh alone. In addition, we show inhibition of the ACh response by cyclic adenosine monophosphate. This is the first quantitative assessment of the effects of these two important transmitters in this system, and it provides an important basis for future analysis of the cellular mechanisms of this well established model for associative olfactory learning. © 2009 Wiley Periodicals, Inc. Develop Neurobiol, 2009 [source] Diet-induced obesity in Sprague,Dawley rats causes microvascular and neural dysfunctionDIABETES/METABOLISM: RESEARCH AND REVIEWS, Issue 4 2010Eric P. Davidson Abstract Background The objective of this study was to determine the effect of diet-induced obesity (DIO) on microvascular and neural function. Methods Rats were fed a standard or high fat diet for up to 32 weeks. The following measurements were carried out: vasodilation in epineurial arterioles using videomicroscopy, endoneurial blood flow using hydrogen clearance, nerve conduction velocity using electrical stimulation, size,frequency distribution of myelinated fibres of the sciatic nerve, intraepidermal nerve fibre density using confocal microscopy and thermal nociception using the Hargreaves method. Results Rats fed a high fat diet for 32 weeks developed sensory neuropathy, as indicated by slowing of sensory nerve conduction velocity and thermal hypoalgesia. Motor nerve conduction velocity and endoneurial blood flow were not impaired. Mean axonal diameter of myelinated fibres of the sciatic nerve was unchanged in high fat-fed rats compared with that in control. Intraepidermal nerve fibre density was significantly reduced in high fat-fed rats. Vascular relaxation to acetylcholine and calcitonin gene-related peptide was decreased and expression of neutral endopeptidase (NEP) increased in epineurial arterioles of rats fed a high fat diet. In contrast, insulin-mediated vascular relaxation was increased in epineurial arterioles. NEP activity was significantly increased in the skin of the hindpaw. Markers of oxidative stress were increased in the aorta and serum of high fat-fed rats but not in epineurial arterioles. Conclusion Chronic obesity causes microvascular and neural dysfunction. This is associated with increased expression of NEP but not oxidative stress in epineurial arterioles. NEP degrades vasoactive peptides, which may explain the decrease in microvascular function. Copyright © 2010 John Wiley & Sons, Ltd. [source] | ||||||||||||||||||||||||||||||||||||||||