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https://www.readbyqxmd.com/read/28734180/bottom-up-assembly-of-salivary-gland-microtissues-for-assessing-myoepithelial-cell-function
#1
Tugba Ozdemir, Padma Pradeepa Srinivasan, Daniel R Zakheim, Daniel A Harrington, Robert L Witt, Mary C Farach-Carson, Xinqiao Jia, Swati Pradhan-Bhatt
Myoepithelial cells are flat, stellate cells present in exocrine tissues including the salivary glands. While myoepithelial cells have been studied extensively in mammary and lacrimal gland tissues, less is known of the function of myoepithelial cells derived from human salivary glands. Several groups have isolated tumorigenic myoepithelial cells from cancer specimens, however, only one report has demonstrated isolation of normal human salivary myoepithelial cells needed for use in salivary gland tissue engineering applications...
July 14, 2017: Biomaterials
https://www.readbyqxmd.com/read/28730966/nicotinic-cholinergic-system-in-the-hypothalamus-modulates-the-activity-of-the-hypothalamic-neuropeptides-during-the-stress-resp
#2
Burcu Balkan, Sakire Pogun
The hypothalamus harbors high levels of cholinergic neurons and axon terminals. Nicotinic acetylcholine receptors, which play an important role in cholinergic neurotransmission, are expressed abundantly in the hypothalamus. Accumulating evidence reveals a regulatory role for nicotine in diverse functions mediated by the hypothalamus, including the regulation of the stress responses. The nicotinic cholinergic system lies at the intersection of homeostatic and reward pathways and shows sex differences in some of its effects...
July 19, 2017: Current Neuropharmacology
https://www.readbyqxmd.com/read/28730896/cannabinoid-hyperemesis-syndrome-potential-mechanisms-for-the-benefit-of-capsaicin-and-hot-water-hydrotherapy-in-treatment
#3
John R Richards, Jeff M Lapoint, Guillermo Burillo-Putze
INTRODUCTION: Cannabinoid hyperemesis syndrome is a clinical disorder that has become more prevalent with increasing use of cannabis and synthetic cannabinoids, and which is difficult to treat. Standard antiemetics commonly fail to alleviate the severe nausea and vomiting characteristic of the syndrome. Curiously, cannabinoid hyperemesis syndrome patients often report dramatic relief of symptoms with hot showers and baths, and topical capsaicin. OBJECTIVES: In this review, we detail the pharmacokinetics and pharmacodynamics of capsaicin and explore possible mechanisms for its beneficial effect, including activation of transient receptor potential vanilloid 1 and neurohumoral regulation...
July 21, 2017: Clinical Toxicology
https://www.readbyqxmd.com/read/28729246/vagally-mediated-effects-of-brainstem-dopamine-on-gastric-tone-and-phasic-contractions-of-the-rat
#4
Laura Anselmi, Luca Toti, Cecilia Bove, R Alberto Travagli
Dopamine (DA) containing fibers and neurons are embedded within the brainstem dorsal vagal complex (DVC); we have shown previously that DA modulates the membrane properties of neurons of the dorsal motor nucleus of the vagus (DMV) via DA1 and DA2 receptors. The vagally-dependent modulation of gastric tone and phasic contractions, i.e. motility, by DA, however, has not been characterized. Using microinjections of DA in the DVC while recording gastric tone and motility, the aims of the present study were: i) assess the gastric effects of brainstem DA application, ii) identify the DA receptor subtype, and, iii) identify the postganglionic pathway(s) activated...
July 20, 2017: American Journal of Physiology. Gastrointestinal and Liver Physiology
https://www.readbyqxmd.com/read/28729220/cognitive-enhancement-and-antipsychotic-like-activity-following-repeated-dosing-with-the-selective-m4-pam-vu0467154
#5
Robert W Gould, Michael D Grannan, Barak W Gunter, Jacob Ball, Michael Bubser, Thomas M Bridges, Jurgen Wess, Michael W Wood, Nicholas J Brandon, Mark E Duggan, Colleen M Niswender, Craig W Lindsley, P Jeffrey Conn, Carrie K Jones
Although selective activation of the M1 muscarinic acetylcholine receptor (mAChR) subtype has been shown to improve cognitive function in animal models of neuropsychiatric disorders, recent evidence suggests that enhancing M4 mAChR function can also improve memory performance. Positive allosteric modulators (PAMs) targeting the M4 mAChR subtype have shown therapeutic potential for the treatment of multiple symptoms observed in schizophrenia, including positive and cognitive symptoms when assessed in acute preclinical dosing paradigms...
July 17, 2017: Neuropharmacology
https://www.readbyqxmd.com/read/28725182/canonical-and-novel-non-canonical-cholinergic-agonists-inhibit-atp-induced-release-of-monocytic-interleukin-1%C3%AE-via-different-combinations-of-nicotinic-acetylcholine-receptor-subunits-%C3%AE-7-%C3%AE-9-and-%C3%AE-10
#6
Anna Zakrzewicz, Katrin Richter, Alisa Agné, Sigrid Wilker, Kathrin Siebers, Bijan Fink, Gabriela Krasteva-Christ, Mike Althaus, Winfried Padberg, Arik J Hone, J Michael McIntosh, Veronika Grau
Recently, we discovered a cholinergic mechanism that inhibits the adenosine triphosphate (ATP)-dependent release of interleukin-1β (IL-1β) by human monocytes via nicotinic acetylcholine receptors (nAChRs) composed of α7, α9 and/or α10 subunits. Furthermore, we identified phosphocholine (PC) and dipalmitoylphosphatidylcholine (DPPC) as novel nicotinic agonists that elicit metabotropic activity at monocytic nAChR. Interestingly, PC does not provoke ion channel responses at conventional nAChRs composed of subunits α9 and α10...
2017: Frontiers in Cellular Neuroscience
https://www.readbyqxmd.com/read/28724203/huprine-x-attenuates-the-neurotoxicity-induced-by-kainic-acid-especially-brain-inflammation
#7
J Relat, B Pérez, P Camps, D Muñoz-Torrero, A Badia, M V Clos
Huprine X (HX) is a synthetic anticholinesterasic compound that exerts a potent inhibitory action on acetylcholinesterase (AChE) activity, an agonist effect on cholinergic receptors, neuroprotective activity in different neurotoxicity models in vivo and in vitro and cognition enhancing effects in non-transgenic (C57BL/6) and transgenic (3xTg-AD, APPswe) mice. In the present study, we assessed the ability of HX (0.8 mg/kg, 21 days) to prevent the damage induced by kainic acid (KA; 28 mg/kg) regarding apoptosis, glia reactivity and neurogenesis in mouse brain...
July 19, 2017: Basic & Clinical Pharmacology & Toxicology
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
#8
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/28721035/intracellular-interactions-of-umeclidinium-and-vilanterol-in-human-airway-smooth-muscle
#9
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
#10
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/28720101/drug-candidates-in-clinical-trials-for-alzheimer-s-disease
#11
REVIEW
Shih-Ya Hung, Wen-Mei Fu
Alzheimer's disease (AD) is a major form of senile dementia, characterized by progressive memory and neuronal loss combined with cognitive impairment. AD is the most common neurodegenerative disease worldwide, affecting one-fifth of those aged over 85 years. Recent therapeutic approaches have been strongly influenced by five neuropathological hallmarks of AD: acetylcholine deficiency, glutamate excitotoxicity, extracellular deposition of amyloid-β (Aβ plague), formation of intraneuronal neurofibrillary tangles (NTFs), and neuroinflammation...
July 19, 2017: Journal of Biomedical Science
https://www.readbyqxmd.com/read/28714717/acetylcholine-contributes-to-the-integration-of-self-movement-cues-in-head-direction-cells
#12
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/28714396/differential-effects-of-nicotine-exposure-on-the-hippocampus-across-lifespan
#13
Dana Zeid, Munir Gunes Kutlu, Thomas J Gould
Nicotine exposure affects the hippocampus through activation of hippocampal nicotinic acetylcholine receptors (nAChRs), which are present throughout excitatory and inhibitory hippocampal circuitry. The role of cholinergic functioning in the hippocampus varies across developmental stages so that nicotine exposure differentially affects this region depending upon timing of exposure, producing developmentally distinct changes in structure, function, and behavior. The hippocampus continues to mature well into adolescence, and this development is modulated by cholinergic activity...
July 13, 2017: Current Neuropharmacology
https://www.readbyqxmd.com/read/28714277/free-fatty-acid-receptor-3-activation-suppresses-neurogenic-motility-in-rat-proximal-colon
#14
I Kaji, Y Akiba, T Furuyama, D W Adelson, K Iwamoto, M Watanabe, A Kuwahara, J D Kaunitz
BACKGROUND: Short-chain fatty acids (SCFA) are microbial fermentation products absorbed by the colon. We recently reported that activation of the SCFA receptor termed free fatty acid receptor 3 (FFA3), expressed on cholinergic nerves, suppresses nicotinic acetylcholine receptor (nAChR)-mediated transepithelial anion secretion. This study aimed to clarify how activation of neurally expressed FFA3 affects colonic motor function. METHODS: FFA3-expressing myenteric neurons were identified by immunostaining; contractions of isolated circular muscle strips obtained from rat proximal colon were measured by isometric transducers...
July 17, 2017: Neurogastroenterology and Motility: the Official Journal of the European Gastrointestinal Motility Society
https://www.readbyqxmd.com/read/28711697/role-of-muscarinic-receptors-in-the-contraction-of-jejunal-smooth-muscle-in-the-horse-an-in-vitro-study
#15
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
#16
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/28696300/acetylcholine-producing-nk-cells-attenuate-cns-inflammation-via-modulation-of-infiltrating-monocytes-macrophages
#17
Wei Jiang, Daojing Li, Ranran Han, Chao Zhang, Wei-Na Jin, Kristofer Wood, Qiang Liu, Fu-Dong Shi, Junwei Hao
The nonneural cholinergic system of immune cells is pivotal for the maintenance of immunological homeostasis. Here we demonstrate the expression of choline acetyltransferase (ChAT) and cholinergic enzymes in murine natural killer (NK) cells. The capacity for acetylcholine synthesis by NK cells increased markedly under inflammatory conditions such as experimental autoimmune encephalomyelitis (EAE), in which ChAT expression escalated along with the maturation of NK cells. ChAT(+) and ChAT(-) NK cells displayed distinctive features in terms of cytotoxicity and chemokine/cytokine production...
July 10, 2017: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/28689815/nicotine-promotes-blood-retinal-barrier-damage-in-a-model-of-human-diabetic-macular-edema
#18
Grazia Maugeri, Agata Grazia D'Amico, Daniela Maria Rasà, Valentina La Cognata, Salvatore Saccone, Concetta Federico, Sebastiano Cavallaro, Velia D'Agata
More than 1 billion world's population actively smokes tobacco containing the bioactive component nicotine (NT). The biological role of this molecule is mediated through the activation of nicotinic cholinergic receptors, widely distributed in various human tissues including retinal pigmented epithelium. The long-term assumption of NT contributes to several diseases development such as diabetic retinopathy. The major complication of this pathology is the diabetic macular edema (DME), characterized by macular area thinning and blood-retinal barrier (BRB) breakdown...
July 6, 2017: Toxicology in Vitro: An International Journal Published in Association with BIBRA
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
#19
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/28685687/modulators-of-acetylcholinesterase-activity-from-alzheimer-s-disease-to-anti-cancer-drugs
#20
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
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