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The important role of Acetylcholine

Christopher M Hearon, Jennifer C Richards, Mathew L Racine, Gary J Luckasen, Dennis G Larson, Frank A Dinenno
KEY POINTS: In humans, the vasodilatory response to skeletal muscle contraction is mediated in part by activation of inwardly rectifying potassium (KIR ) channels. Evidence from animal models suggest that KIR channels serve as electrical amplifiers of endothelium-dependent hyperpolarization (EDH). We found that skeletal muscle contraction amplifies vasodilatation to the endothelium-dependent agonist acetylcholine (ACh), whereas there was no change in the vasodilatory response to sodium nitroprusside, an endothelium-independent nitric oxide donor...
December 1, 2018: Journal of Physiology
Na Yu, Xin Wang, Haibo Bao, Zewen Liu
Insect nicotinic acetylcholine receptors (nAChRs) are not only important neuro-transmitter receptors but also effective insecticide targets. The regulation of nAChRs has been mainly studied in vertebrates especially in mammals. Here, two types of nAChRs were found present in the locust Locusta migratoria mamilensis dorsal unpaired median (DUM) neurons, α-bungarotoxin (α-Bgt)-sensitive nAChRs and α-Bgt-resistant nAChRs, responding to acetylcholine (ACh) at different concentrations. The homologues to three mammalian nAChR regulators, ubiquilin-1, CRELD2 (Cysteine-rich with EFG-like domain 2) and PICK1 (protein interacting with PRKCA 1), were characterised in L...
November 28, 2018: Journal of Neurochemistry
Liqin Zhang, Calvin Wu, David T Martel, Michael West, Michael A Sutton, Susan E Shore
OBJECTIVES: To investigate remodeling of hippocampal cholinergic inputs after noise exposure and determine the relevance of these changes to tinnitus. METHODS: To assess the effects of noise exposure on the hippocampus, guinea pigs were exposed to unilateral noise for two hours and 2 weeks later, immunohistochemistry was performed on hippocampal sections to examine vesicular acetylcholine transporter (VAChT) expression. To evaluate whether the changes in VAChT were relevant to tinnitus, another group of animals was exposed to the same noise band twice to induce tinnitus, which was assessed using gap-prepulse Inhibition of the acoustic startle (GPIAS) 12 weeks after the first noise exposure, followed by immunohistochemistry...
November 24, 2018: Hippocampus
Anu G Nair, Liliana R V Castro, Marianne El Khoury, Victor Gorgievski, Bruno Giros, Eleni T Tzavara, Jeanette Hellgren-Kotaleski, Pierre Vincent
The opposing action of dopamine and acetylcholine has long been known to play an important role in basal ganglia physiology. However, the quantitative analysis of dopamine and acetylcholine signal interaction has been difficult to perform in the native context because the striatum comprises mainly two subtypes of medium-sized spiny neurons (MSNs) on which these neuromodulators exert different actions. We used biosensor imaging in live brain slices of dorsomedial striatum to monitor changes in intracellular cAMP at the level of individual MSNs...
November 22, 2018: Neuropharmacology
Maysa Isernhagen Schaedler, Rhanany Alan Calloi Palozi, Cleide Adriane Signor Tirloni, Aniely Oliveira Silva, Valdinei de Oliveira Araújo, Emerson Luiz Botelho Lourenço, Lauro Mera de Souza, Francislaine Aparecida Dos Reis Lívero, Arquimedes Gasparotto Junior
BACKGROUND: One of the medicinal plants widely used by the population in the treatment of hypertension, atherosclerosis and circulatory disorders is Cuphea carthagenensis (Jacq.) J.F. Macbr. (Lythraceae), popularly known as 'sete sangrias', being found in Brazil, Hawaii and in South Pacific Islands. Despite the widespread use of this species by the population, its long-term antihypertensive and cardioprotective activities have not yet been scientifically evaluated. PURPOSE: To evaluate the possible cardioprotective effects of an ethanol-soluble fraction obtained from C...
December 1, 2018: Phytomedicine: International Journal of Phytotherapy and Phytopharmacology
Shinji Takahashi, Makoto Ohmiya, Sokichi Honda, Keni Ni
N-(4-fluorophenyl)-N'-phenyl-N"-(pyrimidin-2-ylmethyl)-1,3,5-triazine-2,4,6-triamine [ASP2905] is a potent and selective inhibitor of the potassium voltage-gated channel subfamily H member 3 (KCNH3) that was originally identified in our laboratory. KCNH3 is concentrated in the forebrain, and its overexpression in mice leads to cognitive deficits. In contrast, Kcnh3 knockout mice exhibit enhanced performance in cognitive tasks such as attention. These data suggest that KCNH3 plays important roles in cognition...
2018: PloS One
Linjun Wang, Jianghao Xu, Yiwen Xia, Kai Yin, Zheng Li, Bowen Li, Weizhi Wang, Hao Xu, Li Yang, Zekuan Xu
Increasing evidence shows that the vagus nerve plays an important role in tumourigenesis. However, the effects and underlying mechanisms of the vagus nerve on gastric cancer (GC) development have not been established. In this study, we performed a unilateral truncal vagotomy at the subdiaphragmatic level in a mouse xenograft GC model to study the effects of the vagus nerve on GC development. Gene microarray analysis was used to explore the mechanism underlying this process. Significantly altered genes and pathways were analysed by Kyoto Encyclopaedia of Genes and Genomes analysis tool...
November 21, 2018: Oncogenesis
Nan Zhang, Di Gao, Yudan Liu, Sihan Ji, Lei Sha
Purpose: The pancreas is innervated by sensory nerves, parasympathetic and sympathetic nerves. The classical neurotransmitters, acetylcholine and noradrenaline, and some kind of neuropeptides are contained in the terminals of these nerves. Neuropeptides substance P (SP) and calcitonin gene-related peptide (CGRP) co-released from the primary sensory fibers have been identified as the key neurotransmitters in pancreas. Pancreatic ductal epithelium cells are one of the important sources of the pancreatic islet β-cell neogenesis...
2018: Frontiers in Neuroscience
Devon DiPalma, Amir H Rezvani, Blair Willette, Corinne Wells, Susan Slade, Brandon J Hall, Edward D Levin
Tobacco addiction each year causes millions of deaths worldwide. Brain nicotinic acetylcholine receptors have been shown to be central to tobacco addiction. Nicotine replacement therapy aids tobacco cessation, but the success rate is still far too low. This may in part be due to the fact that neurons with nicotinic receptors are not the only neural systems involved in tobacco addiction. Interacting neural systems also play important roles in tobacco addiction. Nicotine increases the release of a variety of neurotransmitters, including dopamine and serotonin...
November 9, 2018: Pharmacology, Biochemistry, and Behavior
Jun Lou, Lei Huang, Aimei Wang, Yueyang Liu, Ruiping Cai, Weihong Li, Ming-Sheng Zhou
Background: Endoplasmic reticulum (ER) stress plays an important role in the pathogenesis of obesity, insulin resistance and cardiovascular diseases (CVDs). Impairment of insulin vascular action may represent a mechanism linking insulin resistance and CVDs. The present study tested the hypothesis that adipocyte-derived resistin inhibits insulin-stimulated endothelial NO production through the induction of ER stress. Methods and Results: Human umbilical vein endothelial cells (HUVC) were incubated with tunicamycin (an inducer of ER stress, 1-20 μg/mL) or resistin (10-100 ng/mL) for 1 h...
2018: Frontiers in Pharmacology
Isabelle Bernard, Antoine Sacquin, Sahar Kassem, Mehdi Benamar, Céline Colacios, Mylène Gador, Corine Pérals, Nicolas Fazilleau, Abdelhadi Saoudi
The guanine nucleotide exchange factor Vav1 is essential for transducing T cell receptor (TCR) signals and plays an important role in T cell development and activation. Previous genetic studies identified a natural variant of Vav1 characterized by the substitution of an arginine (R) residue by a tryptophane (W) at position 63 (Vav1R63W ). This variant impacts Vav1 adaptor functions and controls susceptibility to T cell-mediated neuroinflammation. To assess the implication of this Vav1 variant on the susceptibility to antibody-mediated diseases, we used the animal model of myasthenia gravis, experimental autoimmune myasthenia gravis (EAMG)...
2018: Frontiers in Immunology
Jianrong Xu, Panpan Tan, Hui Li, Yongyao Cui, Yu Qiu, Hao Wang, Xuan Zhang, Juan Li, Liang Zhu, Wei Zhou, Hongzhuan Chen
SUMOylation is a significant post-translational modification (PTM) by the small ubiquitin-related modifier (SUMO). Increasing evidence shows SUMOylation regulates GPCR signaling; however, very few GPCRs have been shown to be SUMOylation targets to date. In this study, we identified M1 muscarinic acetylcholine receptor (M1 mAChR), a member of the GPCRs, as a new SUMO substrate. When the mAChR was activated by the agonist carbachol, the colocalization of the M1 mAChR and SUMO-1 protein markedly decreased in immunoprecipitation and immunofluorescence assays...
November 8, 2018: FASEB Journal: Official Publication of the Federation of American Societies for Experimental Biology
Micah K Callanan, Sarah A Habibi, Wen Jing Law, Kristen Nazareth, Richard L Komuniecki, Sean G Forrester
The cys-loop superfamily of ligand-gated ion channels are well recognized as important drug targets for many invertebrate specific compounds. With the rise in resistance seen worldwide to existing anthelmintics, novel drug targets must be identified so new treatments can be developed. The acetylcholine-gated chloride channel (ACC) family is a unique family of cholinergic receptors that have been shown, using Caenorhabditis elegans as a model, to have potential as anti-parasitic drug targets. However, there is little known about the function of these receptors in parasitic nematodes...
October 27, 2018: International Journal for Parasitology, Drugs and Drug Resistance
Laszlo Záborszky, Peter Gombkoto, Peter Varsanyi, Matthew R Gielow, Gina Poe, Lorna W Role, Mala Ananth, Prithviraj Rajebhosale, David A Talmage, Michael E Hasselmo, Holger Dannenberg, Victor H Minces, Andrea A Chiba
Based on recent molecular genetics, as well as functional and quantitative anatomical studies, the basal forebrain (BF) cholinergic projections, once viewed as a diffuse system, are emerging as being remarkably specific in connectivity. Acetylcholine (ACh) can rapidly and selectively modulate activity of specific circuits and ACh release can be coordinated in multiple areas that are related to particular aspects of cognitive processing. This review discusses how a combination of multiple new approaches with more established techniques are being used to finally reveal how cholinergic neurons, together with other BF neurons, provide temporal structure for behavior, contribute to local cortical state regulation, and coordinate activity between different functionally related cortical circuits...
October 31, 2018: Journal of Neuroscience: the Official Journal of the Society for Neuroscience
James T Brewster, Simone Dell'Acqua, Danny Q Thach, Jonathan L Sessler
The discovery of acetylcholine and acetylcholinesterase provided the first insight into the intricacies of chemical signal transduction and neuronal communication. Further elucidation of the underlying mechanisms led to an attendant leveraging of this knowledge via the synthesis of new therapeutics designed to control aberrant biochemical processes. The central role of the cholinergic system within human memory and learning, as well as its implication in Alzheimer's disease, has made it a point of focus within the neuropharmacology and medicinal chemistry communities...
November 8, 2018: ACS Chemical Neuroscience
Wei Han, Tianxiao Zhang, Tong Ni, Li Zhu, Dan Liu, Gang Chen, Huali Lin, Teng Chen, Fanglin Guan
Altered cholinergic neural transmission is hypothesized to increase susceptibility to cognitive deficits in psychotic disorders such as schizophrenia (SCZ). The nicotinic acetylcholine receptor α5 subunit gene (CHRNA5) is reported to be associated with cognitive function in nicotine-dependent populations and SCZ in non-smoking SCZ patients. Nevertheless, it is still not clear whether the CHRNA5 gene contributes to susceptibility to the cognitive deficits of SCZ without smoking. To further clarify the role of CHRNA5, we designed a two-stage, case-control study to examine the association between CHRNA5 and SCZ and its clinical features adjusted for smoking status in early-onset SCZ patients...
October 23, 2018: Schizophrenia Research
Sevtap Han, Nur Banu Bal, Gökhan Sadi, Suzan Emel Usanmaz, Mecit Orhan Uludag, Emine Demirel-Yilmaz
AIMS: Liver X receptors (LXRs) play an important role in the regulation of cholesterol, fatty acid and glucose metabolisms together with inflammatory processes. In the present study, the effects of LXR agonist GW3965 on vascular reactivity and expression of functional proteins in DOCA-Salt induced hypertension were examined. MAIN METHODS: Hypertension was induced through unilateral nephrectomy and deoxycorticosterone-acetate (DOCA) injection (20 mg/kg, twice a week) for 6 weeks in male Wistar albino rats (8 weeks old)...
October 23, 2018: Life Sciences
Taher Darreh-Shori, Sareh Rezaeianyazdi, Erica Lana, Sumonto Mitra, Anna Gellerbring, Azadeh Karami, Nenad Bogdanovic, Christina Unger Lithner, Bengt Winblad, Homira Behbahani
OMI/HTRA2 (high-temperature requirement serine protease A2) is a mitochondrial serine protease involved in several cellular processes, including autophagy, chaperone activity, and apoptosis. Few studies on the role of OMI/HTRA2 in Alzheimer's disease (AD) are available, but none on its relationship with the cholinergic system and neurotrophic factors as well as other AD-related proteins. In this study, immunohistochemical analyses revealed that AD patients had a higher cytosolic distribution of OMI/HTRA2 protein compared to controls...
October 25, 2018: Molecular Neurobiology
Daniel R Garton, Sharmaine G Ross, Rafael Maldonado-Hernández, Matthias Quick, José A Lasalde-Dominicci, José E Lizardi-Ortiz
Amphetamine-type stimulants (ATS) are the second most consumed illicit drug worldwide and lack good treatments for associated substance use disorders, lagging behind other addictive drugs. For this reason, a deeper understanding of the pharmacodynamics of ATS is required. The present study seeks to determine amphetamine (AMPH) enantiomers' effects on the homomeric α7 nicotinic acetylcholine receptor (α7 nAChR). Here we have shown that AMPH enantiomers bind to the α7 nAChR and competitively inhibit acetylcholine responses...
January 2019: Neuropharmacology
Beryl Y T Chung, Craig D C Bailey
The hippocampal formation (HF) plays an important role to facilitate higher-order cognitive functions. Cholinergic activation of heteromeric nicotinic acetylcholine receptors (nAChRs) within the HF is critical for the normal development of principal neurons within this brain region. However, previous research investigating the expression and function of heteromeric nAChRs in principal neurons of the HF is limited to males or does not differentiate between sexes. We used whole-cell electrophysiology to show that principal neurons in the CA1 region of the female mouse HF are excited by heteromeric nAChRs throughout postnatal development, with the greatest response occurring during the first two weeks of postnatal life...
October 24, 2018: Developmental Neurobiology
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