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Muscarinic receptors

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https://www.readbyqxmd.com/read/28529172/contribution-of-muscarinic-receptors-to-in-vitro-and-in-vivo-effects-of-ruscus-extract
#1
Isabelle Rauly-Lestienne, Peter Heusler, Didier Cussac, Frédérique Lantoine-Adam, Fatima Zely Garcia de Almeida Cyrino, Eliete Bouskela
The objectives of this study were to evaluate, in vitro and in vivo, the contribution of muscarinic receptors to the effects of Ruscus extract. Ruscus extract was tested in competition binding experiments at recombinant human muscarinic receptors, heterologous expressed in Chinese Hamster Ovary (CHO) cells and in cellular assays measuring Ca(2+) liberation and activator protein-1 (AP-1) reporter gene activation. The impact of muscarinic blockade on prolonged treatment outcome was evaluated using the hamster cheek pouch (HCP) microcirculation examining macromolecular permeability increase induced by histamine or ischemia/reperfusion (I/R), mean arteriolar and venular diameters, functional capillary density and I/R-induced leukocyte rolling and sticking...
May 18, 2017: Microvascular Research
https://www.readbyqxmd.com/read/28527783/identification-of-novel-selective-p2y6-receptor-antagonists-by-high-throughput-screening-assay
#2
Masaaki Ito, Shin-Ichiro Egashira, Kazuki Yoshida, Tomoko Mineno, Kazuo Kumagai, Hirotatsu Kojima, Takayoshi Okabe, Tetsuo Nagano, Michio Ui, Isao Matsuoka
AIMS: The P2Y6 nucleotide receptor is widely involved in inflammatory responses, and is a promising molecular target for the treatment of inflammatory diseases. Although several P2Y6 receptor antagonists have been developed and evaluated thus far, none has successfully been developed into a therapeutic drug. In this study, we explored new promising compounds that inhibit the human P2Y6 receptor. MAIN METHODS: High-throughput screening (HTS) was used to study the effects of various compounds on human P2Y6 receptors expressed in 1321N1 human astrocytoma cells by monitoring intracellular Ca(2+) concentration ([Ca(2+)]i) levels using an FDSS7000 real-time fluorescence detector...
May 17, 2017: Life Sciences
https://www.readbyqxmd.com/read/28527131/impact-of-muscarinic-m3-receptor-antagonism-on-the-risk-of-type-2-diabetes-in-antidepressant-treated-patients-a-case-controlled-study
#3
Yen-Hao Tran, Catharina C M Schuiling-Veninga, Jorieke E H Bergman, Henk Groen, Bob Wilffert
BACKGROUND: M3 muscarinic receptor antagonism has been associated with glucose intolerance and disturbance of insulin secretion. OBJECTIVE: Our objective was to examine the risk of type 2 diabetes mellitus (T2DM) in patients using antidepressants with and without M3 muscarinic receptor antagonism (AD_antaM3 and AD_nonantaM3, respectively). METHODS: We designed a case-control study using a pharmacy prescription database. We selected a cohort of patients who initiated antidepressant use between the ages of 20 and 40 years and who did not receive any anti-diabetic prescriptions at baseline...
May 19, 2017: CNS Drugs
https://www.readbyqxmd.com/read/28521906/spinal-cord-regeneration-by-modulating-bone-marrow-with-neurotransmitters-and-citicholine-analysis-at-micromolecular-level
#4
Cheramadathukudiyil Skaria Paulose, Ponnezhathu Sebastian John, Romeo Chinthu, Puthenveetil Raju Akhilraj, Thoppil Raveendran Anju
BACKGROUND: Spinal cord injury results in disruption of brain-spinal cord fibre connectivity, leading to progressive tissue damage at the site of injury and resultant paralysis of varying degrees. The current study investigated the role of autologous bone marrow modulated with neurotransmitters and neurotransmitter stimulating agent, Citicholine, in spinal cord of spinal cord injured rats. METHODS: Radioreceptor assay using [3H] ligand was carried out to quantify muscarinic receptor...
April 2017: Biomedical Journal
https://www.readbyqxmd.com/read/28514645/oleanolic-acid-modulates-the-renin-angiotensin-system-and-cardiac-natriuretic-hormone-concomitantly-with-volume-and-pressure-balance-in-rats
#5
You Mee Ahn, Yoon Hee Choi, Jung Joo Yoon, Yun Jung Lee, Kyung Woo Cho, Dae Gill Kang, Ho Sub Lee
Oleanolic acid is known to possess beneficial effects on the regulation of the cardiovascular homeostasis. However, the exact nature of the role of oleanolic acid on the regulation of body fluid balance and blood pressure homeostasis and its mechanisms involved are not well defined. Experiments were performed to identify the effects of oleanolic acid on the renin-angiotensin system and cardiac natriuretic hormone (ANP) system, and also renal function and blood pressure in normotensive and renovascular hypertensive rats...
May 14, 2017: European Journal of Pharmacology
https://www.readbyqxmd.com/read/28511981/role-of-cholinergic-receptors-in-memory-retrieval-depends-on-gender-and-age-of-memory
#6
Rashid Habiba, Mahboob Aamra, Ahmed Touqeer
The phenomenon of utilizing information acquired in the past to make decision and performance in present depends on memory retrieval, which is affected in retrograde amnesia. Role of cholinergic receptors in memory retrieval is not much explored. In this study we evaluated the gender specific role of cholinergic receptors, i.e. muscarinic and nicotinic receptors, in memory retrieval in young Balb/c mice. Acute (only one injection, 30minutes before test) and sub-chronic (five days) muscarinic blockade (using scopolamine=1mg/kg) before test impaired retrieval of contextual fear memory in male (31...
May 13, 2017: Behavioural Brain Research
https://www.readbyqxmd.com/read/28510314/a-photoswitchable-dualsteric-ligand-controlling-receptor-efficacy
#7
Luca Agnetta, Michael Kauk, Maria Consuelo Alonso Canizal, Regina Messerer, Ulrike Holzgrabe, Carsten Hoffmann, Michael Decker
The investigation of the mode and time course of the activation of G-protein-coupled receptors (GPCRs), in particular muscarinic acetylcholine (mACh or M) receptors, is still in its infancy despite the tremendous therapeutic relevance of M receptors and GPCRs in general. We herein made use of a dualsteric ligand that can concomitantly interact with the orthosteric, that is, the neurotransmitter, binding site and an allosteric one. We synthetically incorporated a photoswitchable (photochromic) azobenzene moiety...
May 16, 2017: Angewandte Chemie
https://www.readbyqxmd.com/read/28506928/distinct-phosphodiesterase-5a-containing-compartments-allow-selective-regulation-of-cgmp-dependent-signalling-in-human-arterial-smooth-muscle-cells
#8
Lindsay S Wilson, Manhong Guo, M Bibiana Umana, Donald H Maurice
Cyclic GMP (cGMP) translates and integrates much of the information encoded by nitric oxide (NO(·)) and several natriuretic peptides, including the atrial natriuretic peptide (ANP). Previously, we reported that integration of a cGMP-specific cyclic nucleotide phosphodiesterase, namely phosphodiesterase 5A (PDE5A), into a protein kinase G (PKG)- and inositol-1,4,5-trisphosphate receptor (IP3R)-containing endoplasmic reticulum (ER) signalosome allows localized control of PDE5A activity and of PKG-dependent inhibition of IP3-mediated release of ER Ca(2+) in human platelets...
May 12, 2017: Cellular Signalling
https://www.readbyqxmd.com/read/28506859/the-obstructed-bladder-expression-of-collagen-matrix-metalloproteinases-muscarinic-receptors-angiogenic-and-neurotrophic-factors-in-patients-with-benign-prostatic-hyperplasia
#9
João Arthur Brunhara Alves Barbosa, Sabrina T Reis, Marco Nunes, Yuri A Ferreira, Katia R Leite, William C Nahas, Miguel Srougi, Alberto A Antunes
OBJECTIVE: to evaluate gene expression of Collagen, Matrix Metalloproteinases (MMP) and Inhibitors, Cholinergic Muscarinic Receptors (CHRM), Angiogenic and Nerve Growth Factors (NGF) in the bladder of patients with Bladder Outlet Obstruction due to Benign Prostatic Hyperplasia METHODS: We analyzed bladder specimens from 43 patients with obstructive BPH undergoing TURP as compared to 10 age-matched controls with IPSS<8 and prostate <30g. A bladder biopsy was performed for relative gene expression analysis with qRT-PCR of Collagens I and III, MMPs 1,2,9; Tissue Inhibitors of Metalloproteinases (TIMP) 1,2 and RECK; CHRM2 and -3; VEGF, CD105; NGF and NGF receptor...
May 12, 2017: Urology
https://www.readbyqxmd.com/read/28505258/modelling-and-mathematical-analysis-of-the-m-_-2-receptor-dependent-joint-signalling-and-secondary-messenger-network-in-cho-cells
#10
Benjamin Engelhardt, Janine Holze, Christina Elliott, George S Baillie, Maik Kschischo, Holger Fröhlich
The muscarinic M$_{2}$ receptor is a prominent member of the GPCR family and strongly involved in heart diseases. Recently published experimental work explored the cellular response to iperoxo-induced M$_{2}$ receptor stimulation in Chinese hamster ovary (CHO) cells. To better understand these responses, we modelled and analysed the muscarinic M$_{2}$ receptor-dependent signalling pathway combined with relevant secondary messenger molecules using mass action. In our literature-based joint signalling and secondary messenger model, all binding and phosphorylation events are explicitly taken into account in order to enable subsequent stoichiometric matrix analysis...
May 15, 2017: Mathematical Medicine and Biology: a Journal of the IMA
https://www.readbyqxmd.com/read/28496430/cholinergic-nociceptive-mechanisms-in-rat-meninges-and-trigeminal-ganglia-potential-implications-for-migraine-pain
#11
Irina Shelukhina, Nikita Mikhailov, Polina Abushik, Leniz Nurullin, Evgeny E Nikolsky, Rashid Giniatullin
BACKGROUND: Parasympathetic innervation of meninges and ability of carbachol, acetylcholine (ACh) receptor (AChR) agonist, to induce headaches suggests contribution of cholinergic mechanisms to primary headaches. However, neurochemical mechanisms of cholinergic regulation of peripheral nociception in meninges, origin place for headache, are almost unknown. METHODS: Using electrophysiology, calcium imaging, immunohistochemistry, and staining of meningeal mast cells, we studied effects of cholinergic agents on peripheral nociception in rat hemiskulls and isolated trigeminal neurons...
2017: Frontiers in Neurology
https://www.readbyqxmd.com/read/28495999/%C3%AE-arrestin-mediated-regulation-of-the-human-ether-a-go-go-related-gene-herg-potassium-channel
#12
Matthew G Sangoi, Shawn M Lamothe, Jun Guo, Tonghua Yang, Wentao Li, Ellen G Avery, John T Fisher, Shetuan Zhang
The rapidly activating delayed rectifier K(+) channel (IKr) is encoded by the human ether-a-go-go-related gene (hERG), which is important for the repolarization of the cardiac action potential. Mutations in hERG or drugs can impair the function or decrease the expression level of hERG channels, leading to long QT syndrome (LQTS). Thus, it is important to understand hERG channel trafficking and its regulation. For this purpose, G protein-coupled receptors (GPCRs), which regulate a vast array of cellular processes, represent a useful route...
May 11, 2017: Molecular Pharmacology
https://www.readbyqxmd.com/read/28491268/umeclidinium-in-chronic-obstructive-pulmonary-disease-latest-evidence-and-place-in-therapy
#13
REVIEW
Kesavan Suresh Babu, Jaymin Bhagwanji Morjaria
Chronic obstructive pulmonary disease (COPD) is a leading cause of morbidity, mortality and health care expenditure throughout the world. COPD guidelines recommend the use of long-acting muscarinic antagonist (LAMA) either alone or in combination with a long-acting β2 agonist (LABA). For over 10 years, tiotropium was the only LAMA that was used in the management of COPD. Over the past few years, various new drugs have been identified that act on the muscarinic receptors and β2 receptors. Umeclidinium (Umec) is a new LAMA currently approved for use in patients with COPD either as monotherapy or in combination with vilanterol (Vil)...
April 2017: Therapeutic Advances in Chronic Disease
https://www.readbyqxmd.com/read/28488564/hippocampal-cholinergic-neurostimulating-peptide-as-a-possible-modulating-factor-against-glutamatergic-neuronal-disability-by-amyloid-oligomers
#14
Toyohiro Sato, Yoshiaki Ohi, Daisuke Kato, Masayuki Mizuno, Hiroshi Takase, Tetsuko Kanamori, Cesar V Borlongan, Akira Haji, Noriyuki Matsukawa
Despite having pathological changes in the brain associated Alzheimer's disease (AD), some patients have preserved cognitive function. A recent epidemiological study has shown that diet, exercise, cognitive training, and vascular risk monitoring interventions may reduce cognitive decline in at-risk elderly people in the general population. However, the details of molecular mechanisms underlying this cognitive function preservation are still unknown. Previous report demonstrated that enriched environments prevent the impairment of hippocampal long-term potentiation (LTP) through β2-adrenergic signals, when LTP is incompletely suppressed by synthetic amyloid-β (Aβ) oligomers...
May 9, 2017: Cell Transplantation
https://www.readbyqxmd.com/read/28474958/-express-dietary-constituent-decanoic-acid-suppresses-the-excitability-of-nociceptive-trigeminal-neuronal-activity-associated-with-hypoalgesia-via-muscarinic-m2-receptor-signaling
#15
Yuna Noguchi, Nichiwa Matsuzawa, Youichi Akama, Kenta Sekiguchi, Shiori Takehana, Yoshihito Shimazu, Mamoru Takeda
No abstract text is available yet for this article.
January 2017: Molecular Pain
https://www.readbyqxmd.com/read/28472227/cortical-nnos-nk1-receptor-neurons-are-regulated-by-cholinergic-projections-from-the-basal-forebrain
#16
Rhîannan H Williams, Jacqueline Vazquez-DeRose, Alexia M Thomas, Juliette Piquet, Bruno Cauli, Thomas S Kilduff
Cholinergic (ACh) basal forebrain (BF) neurons are active during wakefulness and rapid eye movement (REM) sleep and are involved in sleep homeostasis. We have previously shown in adult animals that cortical neurons that express neuronal nitric oxide synthase (nNOS) and the receptor for Substance P (NK1R) are activated during non-REM (NREM) sleep in proportion to homeostatic sleep drive. Here, we show that BF neurons modulate cortical nNOS/NK1R cells. In vitro optogenetic stimulation of BF terminals both activated and inhibited nNOS/NK1R neurons...
May 2, 2017: Cerebral Cortex
https://www.readbyqxmd.com/read/28470123/carbachol-induces-phase-dependent-phase-shifts-of-per1-transcription-rhythms-in-cultured-suprachiasmatic-nucleus-slices
#17
Kumiko Dojo, Yoshiaki Yamaguchi, Jean-Michel Fustin, Masao Doi, Masaki Kobayashi, Hitoshi Okamura
Among nonphotic stimulants, a classic cholinergic agonist, carbachol, is known to have a strong and unique phase-resetting effect on the circadian clock: Intracerebroventricular carbachol treatment causes phase delays during the subjective early night and phase advances in the subjective late night, but the effects of this drug on the suprachiasmatic nucleus (SCN) in vivo and in vitro are still controversial. In the present study, we succeeded in reproducing the biphasic phase-shifting effect of carbachol on clock gene expression in organotypic SCN slices prepared from mice carrying a Per1-promoter fused luciferase gene ( Per1-luc)...
April 2017: Journal of Biological Rhythms
https://www.readbyqxmd.com/read/28463115/decreased-microrna-levels-lead-to-deleterious-increases-in-neuronal-m2-muscarinic-receptors-in-spinal-muscular-atrophy-models
#18
Patrick J O'Hern, Inês do Carmo G Gonçalves, Johanna Brecht, Eduardo Javier López Soto, Jonah Simon, Natalie Chapkis, Diane Lipscombe, Min Jeong Kye, Anne C Hart
Spinal Muscular Atrophy (SMA) is caused by diminished Survival of Motor Neuron (SMN) protein, leading to neuromuscular junction (NMJ) dysfunction and spinal motor neuron (MN) loss. Here, we report that reduced SMN function impacts the action of a pertinent microRNA and its mRNA target in MNs. Loss of the C. elegans SMN ortholog, SMN-1, causes NMJ defects. We found that increased levels of the C. elegans Gemin3 ortholog, MEL-46, ameliorates these defects. Increased MEL-46 levels also restored perturbed microRNA (miR-2) function in smn-1(lf) animals...
May 2, 2017: ELife
https://www.readbyqxmd.com/read/28462392/mechanosensory-stimulation-evokes-acute-concussion-like-behavior-by-activating-girks-coupled-to-muscarinic-receptors-in-a-simple-vertebrate
#19
Wen-Chang Li, Xiao-Yue Zhu, Emma Ritson
Most vertebrates show concussion responses when their heads are hit suddenly by heavy objects. Previous studies have focused on the direct physical injuries to the neural tissue caused by the concussive blow. We study a similar behavior in a simple vertebrate, the Xenopus laevis tadpole. We find that concussion-like behavior can be reliably induced by the mechanosensory stimulation of the head skin without direct physical impacts on the brain. Head skin stimulation activates a cholinergic pathway which then opens G protein-coupled inward-rectifying potassium channels (GIRKs) via postsynaptic M2 muscarinic receptors to inhibit brainstem neurons critical for the initiation and maintenance of swimming for up to minutes and can explain many features commonly observed immediately after concussion...
March 2017: ENeuro
https://www.readbyqxmd.com/read/28461224/responsiveness-to-ipratropium-bromide-in-male-and-female-patients-with-mild-to-moderate-chronic-obstructive-pulmonary-disease
#20
Xuan Li, Ma'en Obeidat, Guohai Zhou, Janice M Leung, Donald Tashkin, Robert Wise, John Connett, Philippe Joubert, Yohan Bossé, Maarten van den Berge, Corry-Anke Brandsma, David C Nickle, Ke Hao, Peter D Paré, Don D Sin
INTRODUCTION: Although the prevalence of chronic obstructive pulmonary disease (COPD) is similar between men and women, current evidence used to support bronchodilator therapy has been generated in therapeutic trials that have predominately enrolled male patients. Here, we determined whether there is any significant sex-related differences in FEV1 responses to ipratropium bromide. METHODS: Data from the Lung Health Study (n=5887; 37% females) were used to determine changes in FEV1 with ipratropium or placebo in male and female subjects with mild to moderate COPD over 5years...
April 12, 2017: EBioMedicine
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