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https://www.readbyqxmd.com/read/29352184/expression-and-relevance-of-the-g-protein-gated-k-channel-in-the-mouse-ventricle
#1
Allison Anderson, Kanchan Kulkarni, Ezequiel Marron Fernandez de Velasco, Nicholas Carlblom, Zhilian Xia, Atsushi Nakano, Kirill A Martemyanov, Elena G Tolkacheva, Kevin Wickman
The atrial G protein-gated inwardly rectifying K+ (GIRK) channel is a critical mediator of parasympathetic influence on cardiac physiology. Here, we probed the details and relevance of the GIRK channel in mouse ventricle. mRNAs for the atrial GIRK channel subunits (GIRK1, GIRK4), M2 muscarinic receptor (M2R), and RGS6, a negative regulator of atrial GIRK-dependent signaling, were detected in mouse ventricle at relatively low levels. The cholinergic agonist carbachol (CCh) activated small GIRK currents in adult wild-type ventricular myocytes that exhibited relatively slow kinetics and low CCh sensitivity; these currents were absent in ventricular myocytes from Girk1-/- or Girk4-/- mice...
January 19, 2018: Scientific Reports
https://www.readbyqxmd.com/read/29351487/contribution-of-parasympathetic-muscarinic-augmentation-of-insulin-secretion-to-olanzapine-induced-hyperinsulinemia
#2
Michael R Rickels, Elys M Perez, Amy J Peleckis, Erica Alshehabi, Huong-Lan Nguyen, Darko Stefanovski, Karl Rickels, Karen L Teff
Atypical antipsychotic drugs have been associated with the development of obesity and diabetes. In particular, olanzapine can induce peripheral insulin resistance and compensatory hyperinsulinemia independent of weight gain or psychiatric disease. To determine if this compensatory increase in insulin is mediated by parasympathetic muscarinic stimulation, we randomized fifteen healthy subjects 2:1 to receive double-blind olanzapine or placebo for 9 days under diet and activity controlled inpatient conditions...
December 19, 2017: American Journal of Physiology. Endocrinology and Metabolism
https://www.readbyqxmd.com/read/29348527/the-human-muscarinic-acetylcholine-receptor-antagonist-dicyclomine-targets-signal-transduction-genes-and-inhibits-the-virulence-factors-in-the-human-pathogen-candida-albicans
#3
Awad Ali, Ashwini Jadhav, Priyanka Jangid, Rajendra Patil, Amruta Shelar, Sankunny Mohan Karuppayil
Dicyclomine is a human muscarinic acetylcholine receptor antagonist used for the treatment of abdominal cramps. We are reporting here that dicyclomine can inhibit the in vitro growth and virulence factors of the human pathogen Candida albicans very effectively. Dicyclomine inhibited adhesion, early biofilm, mature biofilm, and planktonic growth. Yeast to hyphal form transition of C. albicans in various inducer media such as serum, proline, glucose, and N-acetylglucosamine was inhibited. Dicyclomine also could kill C...
January 18, 2018: Journal of Antibiotics
https://www.readbyqxmd.com/read/29344328/management-of-functional-dyspepsia-state-of-the-art-and-emerging-therapies
#4
REVIEW
Hiroshi Yamawaki, Seiji Futagami, Mako Wakabayashi, Noriko Sakasegawa, Shuhei Agawa, Kazutoshi Higuchi, Yasuhiro Kodaka, Katsuhiko Iwakiri
Patients with functional dyspepsia, defined in the 2016 Rome IV criteria as bothersome clinical dyspepsia symptoms, experience markedly reduced quality of life. Several etiologies have been associated with the disorder. In the Rome IV criteria, the brain-gut axis was acknowledged as an important factor in the etiology of functional gastrointestinal (GI) disorders. The distinct subgroups of functional dyspepsia, epigastric pain syndrome (EPS) and postprandial distress syndrome (PDS), are treated differently: acid secretion inhibitors are recommended with patients with EPS, whereas prokinetic drugs as mosapride and acotiamide are recommended for patients with PDS...
January 2018: Therapeutic Advances in Chronic Disease
https://www.readbyqxmd.com/read/29338973/asthma-copd-overlap-a-portuguese-survey
#5
E Padrão, D Araújo, A Todo Bom, C Robalo Cordeiro, J Correia de Sousa, J Cardoso, M Morais-Almeida, R Costa, F Pavão, R B Leite, A Marques
INTRODUCTION: The overlap between asthma and chronic obstructive pulmonary disease (COPD) (ACO) has been discussed for many years but clinical recommendations for this entity have been diverse. This study is intended to reach a consensus on diagnosis, treatment and patient orientation for ACO, within the Portuguese medical community. METHODS: This study was conducted by a multidisciplinary panel of experts from three distinct medical specialties (Pulmonology, Family Medicine and Immunoallergology)...
January 12, 2018: Revista Portuguesa de Pneumologia
https://www.readbyqxmd.com/read/29337266/comparison-of-the-in-vitro-pharmacological-profiles-of-long-acting-muscarinic-antagonists-in-human-bronchus
#6
Emmanuel Naline, Stanislas Grassin Delyle, Hélène Salvator, Marion Brollo, Christophe Faisy, Tatiana Victoni, Charlotte Abrial, Philippe Devillier
BACKGROUND AND PURPOSE: Long-acting muscarinic antagonists (LAMAs) have been recommended for the treatment of chronic obstructive pulmonary disease and (more recently) asthma. However, the in vitro pharmacological profiles of the four LAMAs currently marketed (tiotropium, umeclidinium, aclidinium and glycopyrronium) have not yet been compared (relative to ipratropium) by using the same experimental approach. EXPERIMENTAL APPROACH: With a total of 560 human bronchial rings, we investigated the antagonists' potency, onset and duration of action for inhibition of the contractile response evoked by electrical field stimulation...
January 11, 2018: Pulmonary Pharmacology & Therapeutics
https://www.readbyqxmd.com/read/29335357/nonlinear-relationship-between-spike-dependent-calcium-influx-and-trpc-channel-activation-enables-robust-persistent-spiking-in-neurons-of-the-anterior-cingulate-cortex
#7
Stéphanie Ratté, Sergei Karnup, Steven A Prescott
Persistent spiking - the continuation of spiking after a stimulus ends - is thought to support working memory. Muscarinic receptor activation enables persistent spiking among synaptically isolated pyramidal neurons in anterior cingulate cortex (ACC) but a detailed characterization of that spiking is lacking and the underlying mechanisms remain unclear. Here we show that the rate of persistent spiking in ACC neurons is insensitive to the intensity and number of triggers but can be modulated by injected current, and that persistent spiking can resume after several seconds of hyperpolarization-imposed quiescence...
January 15, 2018: Journal of Neuroscience: the Official Journal of the Society for Neuroscience
https://www.readbyqxmd.com/read/29335337/salivary-glands-regenerate-after-radiation-injury-through-sox2-mediated-secretory-cell-replacement
#8
Elaine Emmerson, Alison J May, Lionel Berthoin, Noel Cruz-Pacheco, Sara Nathan, Aaron J Mattingly, Jolie L Chang, William R Ryan, Aaron D Tward, Sarah M Knox
Salivary gland acinar cells are routinely destroyed during radiation treatment for head and neck cancer that results in a lifetime of hyposalivation and co-morbidities. A potential regenerative strategy for replacing injured tissue is the reactivation of endogenous stem cells by targeted therapeutics. However, the identity of these cells, whether they are capable of regenerating the tissue, and the mechanisms by which they are regulated are unknown. Using in vivo and ex vivo models, in combination with genetic lineage tracing and human tissue, we discover a SOX2+ stem cell population essential to acinar cell maintenance that is capable of replenishing acini after radiation...
January 15, 2018: EMBO Molecular Medicine
https://www.readbyqxmd.com/read/29333036/autonomic-receptors-and-nitric-oxide-involvements-in-mediating-vasorelaxation-effect-induced-by-syzygium-polyanthum-leaves-extract
#9
Azlini Ismail, Wan Amir Nizam Wan Ahmad
Context: Syzygium polyanthum (Wight) Walp leaves are traditionally used by Malays for treating hypertension. Our previous study showed that aqueous extract of S. polyanthum (AESP) and methanolic extract of S. polyanthum (MESP) extracts of S. polyanthum leaves significantly reduced blood pressure of normotensive Wistar-Kyoto (WKY) and spontaneously hypertensive rats (SHR). Aims: This study aimed to investigate their vasorelaxation potential and the possible involvement of autonomic receptors and nitric oxide in mediating their effect...
December 2017: Pharmacognosy Research
https://www.readbyqxmd.com/read/29332320/the-role-of-tiotropium-olodaterol-dual-bronchodilator-therapy-in-the-management-of-chronic-obstructive-pulmonary-disease
#10
REVIEW
David M G Halpin
Bronchodilator therapy is central to the management of chronic obstructive pulmonary disease and are recommended as the preferred treatment by the Global Obstructive Lung Disease Initiative (GOLD). Long acting anti-muscarinics (LAMA) and long acting β₂ agonists (LABA) are both more effective than regular short-acting drugs but many patients remain symptomatic despite monotherapy with these drugs. Combination therapy with LAMA and LABA increases the therapeutic benefit while minimizing dose-dependent side effects of long-acting bronchodilator therapy...
January 2018: Tuberculosis and Respiratory Diseases
https://www.readbyqxmd.com/read/29331508/compartmentalized-crosstalk-of-cftr-and-tmem16a-ano1-through-epac1-and-adcy1
#11
Joana Lérias, Madalena Pinto, Roberta Benedetto, Rainer Schreiber, Margarida Amaral, Massimo Aureli, Karl Kunzelmann
Airway epithelial cells express both Ca2+ activated TMEM16A/ANO1 and cAMP activated CFTR anion channels. Previous work suggested a significant crosstalk of intracellular Ca2+ and cAMP signaling pathways, leading to activation of both chloride channels. We demonstrate that in airway epithelial cells, stimulation of purinergic or muscarinic G-protein coupled receptors (GPCRs) activates TMEM16A and CFTR. Additional expression of Gq/11 and phospholipase C coupled GPCRs strongly enhanced the crosstalk between Ca2+- and cAMP-dependent signaling...
January 10, 2018: Cellular Signalling
https://www.readbyqxmd.com/read/29329111/severe-peri-ictal-respiratory-dysfunction-is-common-in-dravet-syndrome
#12
YuJaung Kim, Eduardo Bravo, Caitlin K Thirnbeck, Lori A Smith-Mellecker, Se Hee Kim, Brian K Gehlbach, Linda C Laux, Douglas R Nordli Jr, George B Richerson
Dravet syndrome (DS) is a severe childhood-onset epilepsy commonly due to mutations of the sodium channel gene SCN1A. DS patients have a high risk of sudden unexplained death in epilepsy (SUDEP), believed to be due to cardiac mechanisms. Here we show that DS patients have peri-ictal respiratory dysfunction. One patient who had severe and prolonged postictal hypoventilation later died of SUDEP. Mice with an Scn1aR1407X/+ loss of function mutation died after spontaneous and heat-induced seizures due to central apnea followed by progressive bradycardia...
January 11, 2018: Journal of Clinical Investigation
https://www.readbyqxmd.com/read/29323700/heat-shock-protein-hsp-regulation-by-muscarinic-acetylcholine-receptor-machr-activation-in-the-rat-hippocampus
#13
Frinchi Monica, Scaduto Pietro, Cappello Francesco, Belluardo Natale, Mudò Giuseppa
The cholinergic system plays a crucial role in modulating in the central nervous system physiological responses such as neurogenesis, neuronal differentiation, synaptic plasticity and neuroprotection. In a recent study, we showed that Oxotremorine-M, a non-selective muscarinic acetylcholine receptor agonist, is able to transactivate the fibroblast growth factor receptor and to produce a significant increase in the hippocampal primary neurite outgrowth. In the present study we aimed to explore in the rat hippocampus the possible effect of acute or chronic treatment with Oxotremorine-M on some heat shock proteins (Hsp60, Hsp70, Hsp90) and on activation of related transcription factor heat shock factor 1 (HSF1)...
January 11, 2018: Journal of Cellular Physiology
https://www.readbyqxmd.com/read/29322375/predictors-of-short-term-lama-ineffectiveness-in-treatment-na%C3%A3-ve-patients-with-moderate-to-severe-copd
#14
Vladimir Fijačko, Marina Labor, Mirjana Fijačko, Sanda Škrinjarić-Cincar, Slavica Labor, Iva Dumbović Dubravčić, Tatjana Bačun, Aleksandar Včev, Sanja Popović-Grle, Davor Plavec
BACKGROUND: No specific (only subgroup) recommendations for the use of long-acting muscarinic antagonists in chronic obstructive pulmonary disease (COPD) exist. The aim of this exploratory hypothesis generating study was to assess whether different phenotypic/endotypic characteristics could be determinants of the short-term ineffectiveness of the initial tiotropium bromide monotherapy in treatment naïve moderate to severe COPD patients. METHODS: A total of 51 consecutively recruited COPD patients were followed for 3 months after the initial evaluation and prescribed initial treatment (tiotropium)...
January 10, 2018: Wiener Klinische Wochenschrift
https://www.readbyqxmd.com/read/29321959/daily-voluntary-exercise-enhances-pilocarpine-induced-saliva-secretion-and-aquaporin-1-expression-in-rat-submandibular-glands
#15
Kentaro Matsuzaki, Naotoshi Sugimoto, Masanori Katakura, Eri Sumiyoshi, Toshiko Hara, Michio Hashimoto, Osamu Shido
Saliva-a water-based fluid containing electrolytes, immunoglobulins, and enzymes-has many functions, including the protection and hydration of mucosal structures within the oral cavity and the initiation of digestion. Aquaporins (AQPs) are proteins that act as water channels through membranes. We have previously reported upregulation of the expression levels of AQP 1 and 5 in the submandibular glands (SMGs) in heat-acclimated rats. In this study, we investigated pilocarpine-induced saliva secretion and AQP expression in rats after voluntary exercise...
January 2018: FEBS Open Bio
https://www.readbyqxmd.com/read/29321572/specific-inhibition-of-acetylcholinesterase-as-an-approach-to-decrease-muscarinic-side-effects-during-myasthenia-gravis-treatment
#16
Konstantin A Petrov, Alexandra D Kharlamova, Oksana A Lenina, Ayrat R Nurtdinov, Marina E Sitdykova, Victor I Ilyin, Irina V Zueva, Evgeny E Nikolsky
Non-selective inhibitors of cholinesterases (ChEs) are clinically used for treatment of myasthenia gravis (MG). While being generally safe, they cause numerous adverse effects including induction of hyperactivity of urinary bladder and intestines affecting quality of patients life. In this study we have compared two ChEs inhibitors, a newly synthesized compound C547 and clinically used pyridostigmine bromide, by their efficiency to reduce muscle weakness symptoms and ability to activate contractions of urinary bladder in a rat model of autoimmune MG...
January 10, 2018: Scientific Reports
https://www.readbyqxmd.com/read/29319226/discovery-of-novel-muscarinic-receptor-modulators-by-integrating-natural-product-framework-with-bioactive-molecule
#17
Rajesh Varkhedkar, Shalini Dogra, Divya Tiwari, Yusuf Hussain, Prem Narayan Yadav, Ganesh Pandey
Muscarinic acetylcholine receptors (mAChRs) are important therapeutic targets for several diseases of central nervous system and periphery. However, lack of subtype selective ligands of these receptors is a major challenge. A novel approach of integrating natural product framework with bioactive molecule (iNPBM) by utilizing the Gephyrotoxin and isoindoline framework, is demonstrated for discovery of new and selective mAChR modulators. We established a scalable and versatile synthetic scheme to enable synthesis of various analogues that provided the first SAR study of this class of compounds...
January 10, 2018: ChemMedChem
https://www.readbyqxmd.com/read/29317054/promising-horizon-to-alleviate-alzeheimer-s-disease-pathological-hallmarks-via-inhibiting-mtor-signaling-pathway-a-new-application-for-a-commonplace-analgesic
#18
Leila Pourtalebi Jahromi, Zahra Sasanipour, Amir Azadi
Alzheimer's disease (AD) is a very prevalent and burdensome disease of elderlies but albeit extensive studies, mechanisms underlying its pathology and consequently its definite treatment is ambiguous. Intra and extra-cellular aggregation of abnormal proteins and impaired autophagy machinery, two closely related events taking place in AD brains proposed to be directly controlled by mTOR signaling pathway. On the other hand, tramadol that is a very well tolerated opioid analgesic has been revealed to inhibit mTOR upstream controllers through interaction with specific types of muscarinic, serotonergic, nicotinic and NMDA receptors, although it seems to induce the opposite effect via µ-opioid receptor...
January 2018: Medical Hypotheses
https://www.readbyqxmd.com/read/29311510/discovery-and-development-of-muscarinic-acetylcholine-m4-activators-as-promising-therapeutic-agents-for-cns-diseases
#19
Kentaro Takai, Takeshi Enomoto
Among the muscarinic acetylcholine receptor (mAChR) subtypes, the M4 receptor has been investigated as a promising drug target for the treatment of schizophrenia. These investigations have been based on findings from M4-deficient mice studies as well as on the results of a clinical trial that used xanomeline, an M1/M4 mAChRs-preferring agonist. Both orthosteric agonists and positive allosteric modulators of M4 mAChR have been reported as promising ligands that not only have antipsychotic effects, but can also improve cognitive impairment and motor dysfunction...
2018: Chemical & Pharmaceutical Bulletin
https://www.readbyqxmd.com/read/29311142/regulation-of-lateral-hypothalamic-orexin-activity-by-local-gabaergic-neurons
#20
Loris L Ferrari, Daniel Park, Lin Zhu, Matthew R Palmer, Rebecca Y Broadhurst, Elda Arrigoni
Orexin (also known as hypocretin) neurons are considered a key component of the ascending arousal system. They are active during wakefulness, at which time they drive and maintain arousal, and are silent during sleep. Their activity is controlled by long-range inputs from many sources, as well as by more short-range inputs, including from presumptive GABAergic neurons in the lateral hypothalamus/perifornical region (LH/PF). To characterize local GABAergic input to orexin neurons we employed channelrhodopsin-2 (ChR2)-assisted-circuit-mapping in brain slices...
January 8, 2018: Journal of Neuroscience: the Official Journal of the Society for Neuroscience
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