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Muscarinic receptors

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https://www.readbyqxmd.com/read/28724783/intra-and-intersegmental-influences-among-central-pattern-generating-networks-in-the-walking-system-of-the-stick-insect
#1
Charalampos Mantziaris, Till Bockemühl, Philip Holmes, Anke Borgmann, Silvia Daun, Ansgar Bueschges
In order to efficiently move around, animals need to coordinate their limbs. Proper, context-dependent coupling among the neural networks underlying leg movement is necessary for generating intersegmental coordination. In the slow-walking stick insect local sensory information is very important for shaping coordination. However, central coupling mechanisms among segmental central pattern generators (CPGs) may also contribute to this. Here, we analyzed the interactions between contralateral networks that drive the depressor trochanteris muscle of the legs in both isolated and interconnected deafferented thoracic ganglia of the stick insect upon application of pilocarpine, a muscarinic acetylcholine receptor agonist...
July 19, 2017: Journal of Neurophysiology
https://www.readbyqxmd.com/read/28722769/promoter-iv-bdnf-deficiency-disturbs-cholinergic-gene-expression-of-chrna5-chrm2-and-chrm5-effects-of-drug-and-environmental-treatments
#2
Kazuko Sakata, Abigail E Overacre
Brain-derived neurotrophic factor (BDNF) promotes maturation of cholinergic neurons. However, how activity-dependent BDNF expression affects specific cholinergic gene expression remains unclear. This study addressed this question by determining mRNA levels of 22 acetylcholine receptor subunits, the choline transporter (CHT), and the choline acetyltransferase (ChAT) in mice deficient in activity-dependent BDNF via promoter IV (KIV) and control wild-type mice. Quantitative RT-PCR revealed significant reductions in nicotinic acetylcholine receptor alpha 5 (CHRNA5) in the frontal cortex and hippocampus and M5 muscarinic acetylcholine receptor (CHRM5) in the hippocampus, but significant increases in M2 muscarinic acetylcholine receptor (CHRM2) in the frontal cortex of KIV mice compared to wild-type mice...
July 19, 2017: Journal of Neurochemistry
https://www.readbyqxmd.com/read/28722259/l-ornithine-and-l-lysine-stimulate-gastrointestinal-motility-via-transient-receptor-potential-vanilloid-1
#3
Junya Nakato, Yee Yin Ho, Ryo Omae, Takafumi Mizushige, Kunitoshi Uchida, Makoto Tominaga, Minji Kim, Tsuyoshi Goto, Nobuyuki Takahashi, Teruo Kawada, Saori Akiduki, Ryuhei Kanamoto, Kousaku Ohinata
SCOPE: The gastrointestinal (GI) tract senses and responds to intraluminal nutrients and these interactions often affect GI functions. We found that, among basic amino acids, L-ornithine (Orn) and L-lysine (Lys) stimulated but L-arginine (Arg) suppressed GI motility after oral administration (24 mmol/kg) in mice (Orn and Lys, 14.3 and 26.4% promotion; Arg, 7.7% suppression). We investigated the mechanism of the action of Orn and Lys on GI motility. METHODS AND RESULTS: Orn-induced promotion of small intestinal transit was significantly inhibited (P<0...
July 18, 2017: Molecular Nutrition & Food Research
https://www.readbyqxmd.com/read/28721035/intracellular-interactions-of-umeclidinium-and-vilanterol-in-human-airway-smooth-muscle
#4
Nooreen Shaikh, Malcolm Johnson, David A Hall, Kian Fan Chung, John H Riley, Sally Worsley, Pankaj K Bhavsar
BACKGROUND: Intracellular mechanisms of action of umeclidinium (UMEC), a long-acting muscarinic receptor antagonist, and vilanterol (VI), a long-acting β2-adrenoceptor (β2R) agonist, were investigated in target cells: human airway smooth-muscle cells (ASMCs). MATERIALS AND METHODS: ASMCs from tracheas of healthy lung-transplant donors were treated with VI, UMEC, UMEC and VI combined, or control compounds (salmeterol, propranolol, ICI 118.551, or methacholine [MCh])...
2017: International Journal of Chronic Obstructive Pulmonary Disease
https://www.readbyqxmd.com/read/28720796/eeg-machine-learning-for-accurate-detection-of-cholinergic-intervention-and-alzheimer-s-disease
#5
Sonja Simpraga, Ricardo Alvarez-Jimenez, Huibert D Mansvelder, Joop M A van Gerven, Geert Jan Groeneveld, Simon-Shlomo Poil, Klaus Linkenkaer-Hansen
Monitoring effects of disease or therapeutic intervention on brain function is increasingly important for clinical trials, albeit hampered by inter-individual variability and subtle effects. Here, we apply complementary biomarker algorithms to electroencephalography (EEG) recordings to capture the brain's multi-faceted signature of disease or pharmacological intervention and use machine learning to improve classification performance. Using data from healthy subjects receiving scopolamine we developed an index of the muscarinic acetylcholine receptor antagonist (mAChR) consisting of 14 EEG biomarkers...
July 18, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28714717/acetylcholine-contributes-to-the-integration-of-self-movement-cues-in-head-direction-cells
#6
Ryan M Yoder, Jeremy H M Chan, Jeffrey S Taube
Acetylcholine contributes to accurate performance on some navigational tasks, but details of its contribution to the underlying brain signals are not fully understood. The medial septal area provides widespread cholinergic input to various brain regions, but selective damage to medial septal cholinergic neurons generally has little effect on landmark-based navigation, or the underlying neural representations of location and directional heading in visual environments. In contrast, the loss of medial septal cholinergic neurons disrupts navigation based on path integration, but no studies have tested whether these path integration deficits are associated with disrupted head direction (HD) cell activity...
August 2017: Behavioral Neuroscience
https://www.readbyqxmd.com/read/28714121/acetylcholine-dependent-upregulation-of-task-1-channels-in-thalamic-interneurons-by-a-smooth-muscle-like-signalling-pathway
#7
Michael Leist, Susanne Rinné, Maia Datunashvili, Ania Aissaoui, Hans-Christian Pape, Niels Decher, Sven G Meuth, Thomas Budde
The dorsal part of the lateral geniculate nucleus (dLGN) is the main thalamic site for state-dependent transmission of visual information. Non-retinal inputs from the ascending arousal system and inhibition provided by γ-aminobutyric acid (GABA)ergic local circuit interneurons (INs) control neuronal activity within the dLGN. In particular, acetylcholine (ACh) depolarizes thalamocortical relay (TC) neurons by inhibiting two-pore domain potassium (K2P ) channels. Conversely, ACh also hyperpolarizes INs via an as-yet-unknown mechanism...
July 17, 2017: Journal of Physiology
https://www.readbyqxmd.com/read/28711697/role-of-muscarinic-receptors-in-the-contraction-of-jejunal-smooth-muscle-in-the-horse-an-in-vitro-study
#8
Alessandro Menozzi, Cristina Pozzoli, Enzo Poli, Giada Bontempi, Paolo Serventi, Valentina Meucci, Luigi Intorre, Simone Bertini
Nonselective antimuscarinic drugs are clinically useful in several pathologic conditions of horses, but, blocking all muscarinic receptor (MR) subtypes, may cause several side effects. The availability of selective antimuscarinic drugs could improve therapeutic efficacy and safety. We aimed to enlighten the role of different MR subtypes by evaluating the effects of nonselective, and selective M1, M2 and M3 MR antagonists on the contractions of horse jejunum. Segments of circular muscle of equine jejunum, were put into organ baths, connected to isotonic transducers, and the effects on ACh concentration-response curves, and on electrical field stimulation (EFS)-evoked contractions of intestinal preparations, induced by nonselective or selective MR antagonists, compared to pre-drug level, were studied...
July 11, 2017: Research in Veterinary Science
https://www.readbyqxmd.com/read/28700094/regulation-of-synaptic-acetylcholine-concentrations-by-acetylcholine-transport-in-rat-striatal-cholinergic-transmission
#9
Ikunobu Muramatsu, Junsuke Uwada, Takayoshi Masuoka, Hatsumi Yoshiki, Kiyonao Sada, Kung-Shing Lee, Matomo Nishio, Takaharu Ishibashi, Takanobu Taniguchi
In addition to hydrolysis by acetylcholine esterase (AChE), acetylcholine (ACh) is also directly taken up into brain tissues. In the present study, we examined whether the uptake of ACh is involved in the regulation of synaptic ACh concentrations. Superfusion experiments with rat striatal segments pre-incubated with [(3) H]choline were performed using an ultra-mini superfusion vessel, which was developed to minimize superfusate retention within the vessel. Hemicholinium-3 (HC-3) at concentrations less than 1 μM, selectively inhibited the uptake of [(3) H]choline by the high affinity-choline transporter 1 (CHT1) and had no effect on basal and electrically evoked [(3) H]efflux in superfusion experiments...
July 12, 2017: Journal of Neurochemistry
https://www.readbyqxmd.com/read/28698560/all-muscarinic-acetylcholine-receptors-m1-m5-are-expressed-in-murine-brain-microvascular-endothelium
#10
Beatrice Mihaela Radu, Antonio Marco Maria Osculati, Eda Suku, Adela Banciu, Grygoriy Tsenov, Flavia Merigo, Marzia Di Chio, Daniel Dumitru Banciu, Cristina Tognoli, Petr Kacer, Alejandro Giorgetti, Mihai Radu, Giuseppe Bertini, Paolo Francesco Fabene
Clinical and experimental studies indicate that muscarinic acetylcholine receptors are potential pharmacological targets for the treatment of neurological diseases. Although these receptors have been described in human, bovine and rat cerebral microvascular tissue, a subtype functional characterization in mouse brain endothelium is lacking. Here, we show that all muscarinic acetylcholine receptors (M1-M5) are expressed in mouse brain microvascular endothelial cells. The mRNA expression of M2, M3, and M5 correlates with their respective protein abundance, but a mismatch exists for M1 and M4 mRNA versus protein levels...
July 11, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28694747/evaluation-of-central-and-peripheral-effects-of-doxepin-on-acetic-acid-induced-colitis-in-rat-and-the-involved-mechanisms
#11
Mohsen Zabihi, Valiollah Hajhashemi, Ardeshir Talebi, Mohsen Minaiyan
Anti-colitis effect of antidepressants has been demonstrated recently. Doxepin, a tricyclic antidepressant drug (TCA), with potent H1, H2, alpha1 adrenergic and muscarinic receptor blocking effects could be a good candidate for investigation for its anti-colitis activity. Moreover high prevalence of depression in patients who suffer from IBD (inflammatory bowel disease), defends this idea that adjuvant therapy with an antidepressant drug which has anti-inflammatory effect, may exert favorable effects in the control of the disease...
2017: EXCLI journal
https://www.readbyqxmd.com/read/28689687/the-effect-of-the-muscarinic-m1-receptor-antagonist-biperiden-on-cognition-in-medication-free-subjects-with-psychosis
#12
Claudia Vingerhoets, Geor Bakker, Jelske van Dijk, Oswald J N Bloemen, Ya Wang, Raymond C K Chan, Jan Booij, Therese A M J van Amelsvoort
The acetylcholine muscarinic M1 receptor has been implicated in both psychosis and cognition. Post-mortem research has shown reduced muscarinic M1 receptor density in 25% of chronic patients with schizophrenia. It is unknown whether reduced M1 receptor density is related to cognitive symptoms of psychosis. We investigated the role of the M1 receptor in separate cognitive domains in subjects with a psychotic disorder using a muscarinic M1 antagonist as an acute pharmacological challenge. 33 young subjects with a psychotic disorder and 30 gender, age and IQ matched healthy controls were enrolled...
July 6, 2017: European Neuropsychopharmacology: the Journal of the European College of Neuropsychopharmacology
https://www.readbyqxmd.com/read/28687907/functional-activation-of-g%C3%AE-q-coupled-to-5-ht2a-receptor-and-m1-muscarinic-acetylcholine-receptor-in-postmortem-human-cortical-membranes
#13
Yuji Odagaki, Masakazu Kinoshita, Toshio Ota, J Javier Meana, Luis F Callado, Jesús A García-Sevilla
Heterotrimeric guanine nucleotide-binding proteins (G-proteins) play a pivotal role in a wide range of signal transduction pathways, and receptor/G-protein coupling has been implicated in the pathophysiology of mental disorders. In this study, guanosine-5'-O-(3-[(35)S]thio)triphosphate ([(35)S]GTPγS) binding/immunoprecipitation assay for Gαq was applied to postmortem human brains. After its optimization for human prefrontal cortical membranes, we selected 5-hydroxytryptamine (5-HT) and carbachol as efficient agonists for subsequent experiments...
July 7, 2017: Journal of Neural Transmission
https://www.readbyqxmd.com/read/28687610/regulator-of-g-protein-signaling-g%C3%AE-5-r7-is-a-crucial-activator-of-muscarinic-m3-receptor-stimulated-insulin-secretion
#14
Qiang Wang, Alexey N Pronin, Konstantin Levay, Joana Almaca, Alessia Fornoni, Alejandro Caicedo, Vladlen Z Slepak
In pancreatic β cells, muscarinic cholinergic receptor M3 (M3R) stimulates glucose-induced secretion of insulin. Regulator of G protein signaling (RGS) proteins are critical modulators of GPCR activity, yet their role in β cells remains largely unknown. R7 subfamily RGS proteins are stabilized by the G protein subunit Gβ5, such that the knockout of the Gnb5 gene results in degradation of all R7 subunits. We found that Gnb5 knockout in mice or in the insulin-secreting MIN6 cell line almost completely eliminates insulinotropic activity of M3R...
July 7, 2017: FASEB Journal: Official Publication of the Federation of American Societies for Experimental Biology
https://www.readbyqxmd.com/read/28686790/adipose-stem-cells-enhance-myoblast-proliferation-via-acetylcholine-and-erk1-2-signaling
#15
Roine El-Habta, Paul J Kingham, Ludvig J Backman
Introduction We investigated the interaction between adipose tissue derived stem cells (ASCs) and myoblasts in co-culture experiments. Methods Specific inductive media were used to differentiate ASCs in vitro into a Schwann cell-like phenotype (dASCs), and subsequently the expression of acetylcholine (ACh) related machinery was determined. Furthermore, the expression of muscarinic ACh receptors (mAChRs) was examined in denervated rat gastrocnemius muscles. Results In contrast to undifferentiated ASCs, dASCs expressed more choline acetyltransferase (ChAT) and vesicular acetylcholine transporter (VAChT)...
July 7, 2017: Muscle & Nerve
https://www.readbyqxmd.com/read/28685687/modulators-of-acetylcholinesterase-activity-from-alzheimer-s-disease-to-anti-cancer-drugs
#16
Tamara Lazarević-Pašti, Andreja Leskovac, Tatjana Momić, Sandra Petrović, Vesna Vasić
BACKGROUND: Acetylcholinesterase (AChE) is involved in the termination of impulse transmission by rapid hydrolysis of the neurotransmitter acetylcholine in numerous cholinergic pathways in the central and peripheral nervous systems. The enzyme inactivation leads to acetylcholine accumulation, hyperstimulation of nicotinic and muscarinic receptors, and disrupted neurotransmission. Hence, acetylcholinesterase inhibitors, interacting with the enzyme as their primary target, are applied as relevant drugs for different neurodegenerative diseases (such as Alzheimer's and Parkinson's) as well as toxins...
July 5, 2017: Current Medicinal Chemistry
https://www.readbyqxmd.com/read/28681521/changes-of-bladder-m1-3-muscarinic-receptor-expression-in-rats-fed-with-short-term-long-term-high-fat-diets
#17
Chian-Shiung Lin, Tony T-L Wu, Chin-Hong Chang, Juei-Tang Cheng, Yat-Ching Tong
OBJECTIVES: To investigate the effect of high-fat diet (HFD) on bladder M1,3 muscarinic receptor expression and contractile function in the rat. METHODS: Eight-week-old male rats were divided into two groups including one with HFD for 8 weeks (short-term) and the other for 24 weeks (long-term). Each group was compared to age-matched rats fed with normal chow as controls. The body weight, food intake amount and blood biochemistry were monitored. Bladder muscle contractile responses to acetylcholine (0...
July 5, 2017: Lower Urinary Tract Symptoms
https://www.readbyqxmd.com/read/28680403/scopolamine-induces-deficits-in-spontaneous-object-location-recognition-and-fear-learning-in-marmoset-monkeys
#18
Jonathan L Melamed, Fernando M de Jesus, Rafael S Maior, Marilia Barros
The non-selective muscarinic receptor antagonist scopolamine (SCP) induces memory deficits in both animals and humans. However, few studies have assessed the effects of amnesic agents on memory functions of marmosets - a small-bodied neotropical primate that is becoming increasingly used as a translational model for several neuropathologies. Here we assessed the effects of an acute SCP administration (0.03 mg/kg, sc) on the behavior of adult marmoset monkeys in two tasks. In the spontaneous object-location (SOL) recognition task, two identical neutral stimuli were explored on the sample trial, after which preferential exploration of the displaced versus the stationary object was analyzed on the test trial...
2017: Frontiers in Pharmacology
https://www.readbyqxmd.com/read/28680103/chemogenetic-silencing-of-gabaergic-dorsal-horn-interneurons-induces-morphine-resistant-spontaneous-nocifensive-behaviours
#19
Keisuke Koga, Kensho Kanehisa, Yuta Kohro, Miho Shiratori-Hayashi, Hidetoshi Tozaki-Saitoh, Kazuhide Inoue, Hidemasa Furue, Makoto Tsuda
Inhibitory interneurons in the spinal dorsal horn (SDH) are crucial for processing somatosensory information originating in the periphery. However, the effects of the acute and selective inactivation of GABAergic SDH interneurons on pain processing are not fully understood. In this study, we used designer receptors exclusively activated by designer drugs (DREADD) technology and vesicular GABA transporter-Cre (Vgat-Cre) mice to selectively express a modified human muscarinic Gi protein-coupled receptor (hM4Di) in Vgat-Cre (+) GABAergic SDH interneurons in the fourth lumbar segment...
July 5, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28679049/role-of-mglu5-receptors-and-inhibitory-neurotransmission-in-m1-dependent-muscarinic-ltd-in-the-prefrontal-cortex-implications-in-schizophrenia
#20
Ayan Ghoshal, Sean P Moran, Jonathan W Dickerson, Max E Joffe, Brad A Grueter, Zixiu Xiang, Craig W Lindsley, Jerri M Rook, P Jeffrey Conn
Selective potentiation of the mGlu5 subtype of metabotropic glutamate (mGlu) receptor using positive allosteric modulators (PAMs) has robust cognition-enhancing effects in rodent models that are relevant for schizophrenia. Until recently, these effects were thought to be due to potentiation of mGlu5-induced modulation of NMDA receptor (NMDAR) currents and NMDAR-dependent synaptic plasticity. However, "biased" mGlu5 PAMs that do not potentiate mGlu5 effects on NMDAR currents show efficacy that is similar to that of prototypical mGlu5 PAMs, suggesting that NMDAR-independent mechanisms must be involved in these actions...
July 5, 2017: ACS Chemical Neuroscience
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