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Muscarinic receptors

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https://www.readbyqxmd.com/read/28342980/muscarinic-receptor-mediated-signaling-pathways-in-hepatocytes-from-ccl4-induced-liver-fibrotic-rat
#1
Lin Luo, Chenghao Xi, Tingting Xu, Gaoshan Zhang, E Qun, Wei Zhang
The pathological changes of parasympathetic nerves are considered as an independent prognostic factor of the survival rate for patients with chronic liver disease. The non-selective muscarinic acetylcholine receptors (mAchR) agonists and antagonists can affect the proliferation of hepatocytes, but little is known about the role of mAChR in hepatocytes and hepatic fibrosis and the signaling pathway of this receptor in regulation of hepatocytes remains elusive. Here, 3ml/kg 40% carbon tetrachloride (CCL4) was given to induce hepatic fibrosis in rats and the hepatocytes were isolated to investigate the expression of mAchR and the cell signaling pathways which were involved in...
March 22, 2017: European Journal of Pharmacology
https://www.readbyqxmd.com/read/28341945/translational-value-of-drug-discrimination-with-typical-and-atypical-antipsychotic-drugs
#2
Joseph H Porter, Kevin A Webster, Adam J Prus
This chapter focuses on the translational value of drug discrimination as a preclinical assay for drug development. In particular, the importance of two factors, i.e., training dose and species, for drug discrimination studies with the atypical antipsychotic clozapine is examined. Serotonin receptors appear to be an important pharmacological mechanism mediating clozapine's discriminative cue in both rats and mice, although differences are clearly evident as antagonism of cholinergic muscarinic receptors is important in rats at a higher training dose (5...
March 25, 2017: Current Topics in Behavioral Neurosciences
https://www.readbyqxmd.com/read/28336323/m1-muscarinic-activation-induces-long-lasting-increase-in-intrinsic-excitability-of-striatal-projection-neurons
#3
Xiaohui Lv, Jonathan W Dickerson, Jerri M Rook, Craig W Lindsley, P Jeffrey Conn, Zixiu Xiang
The dorsolateral striatum is critically involved in movement control and motor learning. Striatal function is regulated by a variety of neuromodulators including acetylcholine. Previous studies have shown that cholinergic activation excites striatal principal projection neurons, medium spiny neurons (MSNs), and this action is mediated by muscarinic acetylcholine subtype 1 receptors (M1) through modulating multiple potassium channels. In the present study, we used electrophysiology techniques in conjunction with optogenetic and pharmacological tools to determine the long-term effects of striatal cholinergic activation on MSN intrinsic excitability...
March 20, 2017: Neuropharmacology
https://www.readbyqxmd.com/read/28334356/transient-cell-intrinsic-activity-regulates-the-migration-and-laminar-positioning-of-cortical-projection-neurons
#4
Nicolas Hurni, Marta Kolodziejczak, Ugo Tomasello, Joan Badia, Moritz Jacobshagen, Julien Prados, Alexandre Dayer
Neocortical microcircuits are built during development and require the coordinated assembly of excitatory glutamatergic projection neurons (PNs) into functional networks. Neuronal migration is an essential step in this process. In addition to cell-intrinsic mechanisms, external cues including neurotransmitters regulate cortical neuron migration, suggesting that early activity could influence this process. Here, we aimed to investigate the role of cell-intrinsic activity in migrating PNs in vivo using a designer receptor exclusively activated by a designer drug (DREADD) chemogenetic approach...
March 17, 2017: Cerebral Cortex
https://www.readbyqxmd.com/read/28332063/decreased-interaction-between-zo-1-and-occludin-is-involved-in-alteration-of-tight-junctions-in-transplanted-epiphora-submandibular-glands
#5
Chong Ding, Xin Cong, Xue-Ming Zhang, Sheng-Lin Li, Li-Ling Wu, Guang-Yan Yu
Tight junctions (TJs) in salivary epithelium play an important role in regulating saliva secretion. Autologous transplantation of submandibular glands (SMGs) is an effective method to treat severe dry eye syndrome. However, epiphora occurs in some patients 6 months after transplantation. We previously found that the acinar TJs are enlarged in rabbit SMGs after long-term transplantation, but the exact TJ components involved in the epiphora are still unknown. Here, we found that the mRNA and protein expression of ZO-1 and occludin were increased in the transplanted SMGs obtained from epiphora patients, while other TJs were unchanged...
March 22, 2017: Journal of Molecular Histology
https://www.readbyqxmd.com/read/28328743/acetylcholine-atropine-interactions-paradoxical-effects-on-atrial-fibrillation-inducibility
#6
Yu Liu, Benjamin J Scherlag, Youqi Fan, Wenfang Xia, He Huang, Sunny S Po
Atropine (ATr) is well known as a cholinergic antagonist, however, at low concentrations ATr could paradoxically accentuate the parasympathetic actions of acetylcholine (ACh). In 22 pentobarbital anesthetized dogs, via a left and right thoracotomy, a leak proof barrier was attached to isolate the atrial appendages (AAs) from the rest of the atria. In Group 1(Ach+ATr+Ach), ACh, 100 mM, was placed on the AA followed by the application of ATr, 2mg/cc. The average AFdur was 17±7 minutes. After ATr was applied to the AA and ACh again tested, the AFdur was markedly attenuated (2±2 minutes, p<0...
March 21, 2017: Journal of Cardiovascular Pharmacology
https://www.readbyqxmd.com/read/28326934/activations-of-muscarinic-m1-receptors-in-the-anterior-cingulate-cortex-contribute-to-the-antinociceptive-effect-via-gabaergic-transmission
#7
Kohei Koga, Yu Matsuzaki, Kenji Honda, Fumihiro Eto, Tomonori Furukawa, Keisuke Migita, Keiichi Irie, Kenichi Mishima, Shinya Ueno
Background Cholinergic systems regulate the synaptic transmission resulting in the contribution of the nociceptive behaviors. Anterior cingulate cortex is a key cortical area to play roles in nociception and chronic pain. However, the effect of the activation of cholinergic system for nociception is still unknown in the cortical area. Here, we tested whether the activation of cholinergic receptors can regulate nociceptive behaviors in adult rat anterior cingulate cortex by integrative methods including behavior, immunohistochemical, and electrophysiological methods...
January 2017: Molecular Pain
https://www.readbyqxmd.com/read/28326549/the-three-finger-toxin-fold-a-multifunctional-structural-scaffold-able-to-modulate-cholinergic-functions
#8
REVIEW
Pascal Kessler, Pascale Marchot, Marcela Silva, Denis Servent
Three-finger fold toxins are miniproteins frequently found in Elapidae snake venoms. This fold is characterized by three distinct loops rich in β-strands and emerging from a dense, globular core reticulated by four highly conserved disulfide bridges. The number and diversity of receptors, channels, and enzymes identified as targets of three-finger fold toxins is increasing continuously. Such manifold diversity highlights the specific adaptability of this fold for generating pleiotropic functions. Although this toxin superfamily disturbs many biological functions by interacting with a large diversity of molecular targets, the most significant target is the cholinergic system...
March 21, 2017: Journal of Neurochemistry
https://www.readbyqxmd.com/read/28324647/metabolism-and-distribution-of-clozapine-n-oxide-implications-for-nonhuman-primate-chemogenetics
#9
Jessica Raper, J Scott Daniels, Ryan D Morrison, Leonard Howell, Jocelyne Bachevalier, Thomas Wichmann, Adriana Galvan
The use of Designer Receptors Exclusively Activated by Designer Drugs (DREADDs) in neuroscience has rapidly expanded in rodent studies, but has lagged behind in nonhuman primate (NHP) experiments, slowing the development of this method for therapeutic use in humans. One reason for the slow adoption of DREADD technology in primates is that the pharmacokinetic properties and bioavailability of clozapine-n-oxide (CNO), the most commonly used ligand for human muscarinic (hM) DREADDs, are not fully described in primates...
March 21, 2017: ACS Chemical Neuroscience
https://www.readbyqxmd.com/read/28315343/inhibition-of-agonist-induced-smooth-muscle-contraction-by-picotamide-in-the-male-human-lower-urinary-tract-outflow-region
#10
Martin Hennenberg, Alexander Tamalunas, Yiming Wang, Patrick Keller, Melanie Schott, Frank Strittmatter, Annika Herlemann, Qingfeng Yu, Beata Rutz, Anna Ciotkowska, Christian G Stief, Christian Gratzke
Male lower urinary tract symptoms (LUTS) due to bladder outlet obstruction are characterized by abnormal smooth muscle contractions in the lower urinary tract. Alpha1-adrenoceptor antagonists may induce smooth muscle relaxation in the outflow region and represent the current goldstandard of medical treatment. However, results may be unsatisfactory or inadequate. Apart from α1-adrenoceptor agonists, smooth muscle contraction in the outflow region may be induced by thromboxane A2 (TXA2), endothelins, or muscarinic receptor agonists...
March 14, 2017: European Journal of Pharmacology
https://www.readbyqxmd.com/read/28315276/the-sigma-1-receptor-a-therapeutic-target-for-the-treatment-of-als
#11
Timur A Mavlyutov, Erin M Baker, Tasher M Losenegger, Jaimie R Kim, Brian Torres, Miles L Epstein, Arnold E Ruoho
The membrane bound 223 amino acid Sigma-1 Receptor (S1R) serves as a molecular chaperone and functional regulator of many signaling proteins. Spinal cord motor neuron activation occurs, in part, via large ventral horn cholinergic synapses called C-boutons/C-terminals. Chronic excitation of motor neurons and alterations in C-terminals has been associated with Amyotrophic Lateral Sclerosis (ALS ). The S1R has an important role in regulating motor neuron function. High levels of the S1R are localized in postsynaptic endoplasmic reticulum (ER) subsurface cisternae within 10-20 nm of the plasma membrane that contain muscarinic type 2 acetylcholine receptors (M2AChR), calcium activated potassium channels (Kv2...
2017: Advances in Experimental Medicine and Biology
https://www.readbyqxmd.com/read/28302036/pharmacological-effects-of-turmeric-on-learning-memory-and-expression-of-muscarinic-receptor-genes-m1-m3-and-m5-in-stress-induced-mouse-model
#12
Aliya Khalid, Rabia Shakeel, Saira Justin, Ghazala Iqbal, Syed Adnan Ali Shah, Saadia Zahid, Touqeer Ahmed
Stress is involved in memory impairment by multiple mechanisms including activation of Hypothalamic-Pituitary Axis, which in turn activates release of corticosterone in blood. Cholinergic system blockade by muscarinic antagonist like scopolamine, also impairs memory. AIM: This study aimed to investigate the effect of turmeric (20mg/kg) on learning and memory and cholinergic system in a mouse model of stress along with cholinergic blockade. METHODS: Restrained stress was induced and cholinergic receptors were blocked using scopolamine in mice...
March 15, 2017: Current Drug Targets
https://www.readbyqxmd.com/read/28301610/the-effects-of-substance-p-and-acetylcholine-on-human-tenocyte-proliferation-converge-mechanistically-via-tgf-%C3%AE-1
#13
Gloria Fong, Ludvig J Backman, Håkan Alfredson, Alex Scott, Patrik Danielson
Previous in vitro studies on human tendon cells (tenocytes) have demonstrated that the exogenous administration of substance P (SP) and acetylcholine (ACh) independently result in tenocyte proliferation, which is a prominent feature of tendinosis. Interestingly, the possible link between SP and ACh has not yet been explored in human tenocytes. Recent studies in other cell types demonstrate that both SP and ACh independently upregulate TGF-β1 expression via their respective receptors, the neurokinin 1 receptor (NK-1R) and muscarinic ACh receptors (mAChRs)...
2017: PloS One
https://www.readbyqxmd.com/read/28299422/homeostatic-regulation-through-gaba-and-acetylcholine-muscarinic-receptors-of-motor-trigeminal-neurons-following-sleep-deprivation
#14
Hanieh Toossi, Esther Del Cid-Pellitero, Barbara E Jones
Muscle tone is regulated across sleep-wake states, being maximal in waking, reduced in slow wave sleep (SWS) and absent in paradoxical or REM sleep (PS or REMS). Such changes in tone have been recorded in the masseter muscles and shown to correspond to changes in activity and polarization of the trigeminal motor 5 (Mo5) neurons. The muscle hypotonia and atonia during sleep depend in part on GABA acting upon both GABAA and GABAB receptors (Rs) and acetylcholine (ACh) acting upon muscarinic 2 (AChM2) Rs. Here, we examined whether Mo5 neurons undergo homeostatic regulation through changes in these inhibitory receptors following prolonged activity with enforced waking...
March 15, 2017: Brain Structure & Function
https://www.readbyqxmd.com/read/28294051/further-evaluation-of-mechanisms-associated-with-the-antidepressant-like-signature-of-scopolamine-in-mice
#15
Anna E Martin, Douglas A Schober, Alexander Nikolayev, Vladimir V Tolstikov, Wesley H Anderson, Richard E Higgs, Ming-Shang Kuo, Anastasia Laksmanan, John T Catlow, Xia Li, Christian C Felder, Jeffrey M Witkin
Conventional antidepressants lack efficacy for many patients (treatment-resistant depression or TRD) and generally take weeks to produce full therapeutic response in others. Emerging data has identified certain drugs such as ketamine as rapidly-acting antidepressants for major depressive disorder and TRD. Scopolamine, a drug used to treat motion sickness and nausea, has also been demonstrated to function as a rapidly-acting antidepressant. The mechanisms associated with efficacy in TRD patients and rapid onset of action have been suggested to involve a-Amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) receptor and mammalian target of rapamycin (mTOR) signaling...
March 9, 2017: CNS & Neurological Disorders Drug Targets
https://www.readbyqxmd.com/read/28293176/muscarinic-receptors-are-responsible-for-the-cholinergic-modulation-of-projection-neurons-in-the-song-production-brain-nucleus-ra-of-zebra-finches
#16
Wei Meng, Songhua Wang, Lihua Yao, Nan Zhang, Dongfeng Li
Songbirds are a useful model for the study of learned vocal behavior in vertebrates. The robust nucleus of the arcopallium (RA) is a premotor nucleus in the vocal motor pathway. It receives excitatory synaptic inputs from the anterior forebrain pathway. RA also receives cholinergic inputs from the ventral paleostriatum of the basal forebrain. Our previous study showed that carbachol, a non-selective cholinergic receptor agonist, modulates the electrophysiology of RA projection neurons (PNs), indicating that cholinergic modulation of RA may play an important role in song production...
2017: Frontiers in Cellular Neuroscience
https://www.readbyqxmd.com/read/28284954/peri-adolescent-asthma-symptoms-cause-adult-anxiety-related-behavior-and-neurobiological-processes-in-mice
#17
Jasmine I Caulfield, Michael J Caruso, Kerry C Michael, Rebecca A Bourne, Nicole R Chirichella, Laura C Klein, Timothy Craig, Robert H Bonneau, Avery August, Sonia A Cavigelli
Human and animal studies have shown that physical challenges and stressors during adolescence can have significant influences on behavioral and neurobiological development associated with internalizing disorders such as anxiety and depression. Given the prevalence of asthma during adolescence and increased rates of internalizing disorders in humans with asthma, we used a mouse model to test if and which symptoms of adolescent allergic asthma (airway inflammation or labored breathing) cause adult anxiety- and depression-related behavior and brain function...
March 8, 2017: Behavioural Brain Research
https://www.readbyqxmd.com/read/28284659/diuretic-natriuretic-and-potassium-sparing-effect-of-nothofagin-isolated-from-leandra-dasytricha-a-gray-cogn-leaves-in-normotensive-and-hypertensive-rats
#18
Camila Leandra Bueno de Almeida, Thaise Boeing, Lincon Bordignon Somensi, Viviane Miranda Bispo Steimbach, Luísa Mota da Silva, Sérgio Faloni de Andrade, Franco Delle Monache, Valdir Cechinel-Filho, Priscila de Souza
Active constituents from natural origin have long been used for the treatment of patients suffering from cardiovascular and renal diseases. This study therefore aimed to investigate the diuretic and natriuretic properties of nothofagin, a dihydrochalcone isolated from Leandra dasytricha (A. Gray) Cogn. leaves in normotensive and hypertensive rats. Male Wistar normotensive rats were orally treated with vehicle (1 ml/kg); hydrochlorothiazide (HCTZ; 25 mg/kg); ethyl acetate fraction from L. dasytricha (EALD; 3-30 mg/kg) and nothofagin (NOT; 0...
March 8, 2017: Chemico-biological Interactions
https://www.readbyqxmd.com/read/28284212/combination-of-glycopyrronium-and-indacaterol-inhibits-carbachol-induced-erk5-signal-in-fibrotic-processes
#19
Yukiko Namba, Shinsaku Togo, Miniwan Tulafu, Kotaro Kadoya, Kumi Yoneda Nagahama, Hikari Taka, Naoko Kaga, Akira Orimo, Xiangde Liu, Kazuhisa Takahashi
BACKGROUND: Airway fibrosis is one of the pathological features of chronic obstructive pulmonary disease (COPD), and recent studies revealed that acetylcholine plays an important role in the development of airway remodeling by stimulating proliferation and collagen synthesis of lung fibroblasts. This study was designed to examine the effects of a long-acting muscarinic receptor antagonist (LAMA) glycopyrronium and a long-acting β2 adrenergic receptor agonist (LABA) indacaterol on acetylcholine-mediated fibrotic responses in lung fibroblasts...
March 11, 2017: Respiratory Research
https://www.readbyqxmd.com/read/28281385/electroacupuncture-brain-protection-during-ischemic-stroke-a-role-for-the-parasympathetic-nervous-system
#20
Laiting Chi, Kairong Du, Dongdong Liu, Yulong Bo, Wenzhi Li
The demand for using parasympathetic activation for stroke therapy is unmet. In the current study, we investigated whether the neuroprotection provided by electroacupuncture (EA) in an experimental stroke model was associated with activation of the parasympathetic nervous system (PNS). The results showed that parasympathetic dysfunction (PD), performed as unilateral vagotomy combined with peripheral atropine, attenuated both the functional benefits of EA and its effects in improving cerebral perfusion, reducing infarct volume, and hindering apoptosis, neuronal and peripheral inflammation, and oxidative stress...
January 1, 2017: Journal of Cerebral Blood Flow and Metabolism
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