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Muscarinic receptors

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https://www.readbyqxmd.com/read/28932225/expression-and-function-of-the-cholinergic-system-in-immune-cells
#1
REVIEW
Takeshi Fujii, Masato Mashimo, Yasuhiro Moriwaki, Hidemi Misawa, Shiro Ono, Kazuhide Horiguchi, Koichiro Kawashima
T and B cells express most cholinergic system components-e.g., acetylcholine (ACh), choline acetyltransferase (ChAT), acetylcholinesterase, and both muscarinic and nicotinic ACh receptors (mAChRs and nAChRs, respectively). Using ChAT(BAC)-eGFP transgenic mice, ChAT expression has been confirmed in T and B cells, dendritic cells, and macrophages. Moreover, T cell activation via T-cell receptor/CD3-mediated pathways upregulates ChAT mRNA expression and ACh synthesis, suggesting that this lymphocytic cholinergic system contributes to the regulation of immune function...
2017: Frontiers in Immunology
https://www.readbyqxmd.com/read/28928637/alpha7-nicotinic-acetylcholine-receptors-play-a-predominant-role-in-the-cholinergic-potentiation-of-n-methyl-d-aspartate-evoked-firing-responses-of-hippocampal-ca1-pyramidal-cells
#2
Zsolt K Bali, Lili V Nagy, István Hernádi
The aim of the present study was to identify in vivo electrophysiological correlates of the interaction between cholinergic and glutamatergic neurotransmission underlying memory. Extracellular spike recordings were performed in the hippocampal CA1 region of anesthetized rats in combination with local microiontophoretic administration of N-methyl-D-aspartate (NMDA) and acetylcholine (ACh). Both NMDA and ACh increased the firing rate of the neurons. Furthermore, the simultaneous delivery of NMDA and ACh resulted in a more pronounced excitatory effect that was superadditive over the sum of the two mono-treatment effects and that was explained by cholinergic potentiation of glutamatergic neurotransmission...
2017: Frontiers in Cellular Neuroscience
https://www.readbyqxmd.com/read/28921504/g%C3%AE-12-facilitates-carbachol-induced-shortening-in-human-airway-smooth-muscle-by-modulating-phosphoinositide-3-kinase-mediated-activation-in-a-rhoa-dependent-manner
#3
Edwin J Yoo, Gaoyuan Cao, Cynthia J Koziol-White, Christie A Ojiaku, Krishna Sunder, Joseph A Jude, James V Michael, Hong Lam, Ivan Pushkarsky, Robert Damoiseaux, Dino Di Carlo, Kwangmi Ahn, Steven S An, Raymond B Penn, Reynold A Panettieri
BACKGROUND AND PURPOSE: Phosphoinositide 3-kinase (PI3K)-dependent activation of Rho kinase (ROCK) is necessary for agonist-induced human airway smooth muscle cell (HASMC) contraction, and inhibition of PI3K promotes bronchodilation of human small airways. The upstream mechanisms driving agonist-mediated PI3K/ROCK axis activation, however, remain unclear. Given the capacity of G12 family proteins to activate ROCK pathways in other cell types (Riobo and Manning, 2005), the role of G12 proteins in modulating M3 muscarinic acetylcholine receptor (M3R)-stimulated PI3K/ROCK activation and HASMC contraction was examined...
September 17, 2017: British Journal of Pharmacology
https://www.readbyqxmd.com/read/28917975/the-memory-ameliorating-effects-of-dhp1402-an-herbal-mixture-on-cholinergic-blockade-induced-cognitive-dysfunction-in-mice
#4
Haneul Kim, Hyung Eun Lee, In Ho Jung, Se Jin Jeon, Jiabao Zhang, Yubeen Kwon, Dae Sik Jang, Jong Hoon Ryu
ETHNOPHARMACOLOGICAL RELEVANCE: Ziziphus jujuba var. spinosa (Bunge) Hu ex H.F Chow (rhamnaceae) and Codonopsis lanceolata (Siedbold & Zucc.) Benth. & Hook.f. ex Trautv. (campanulaceae), compositions of DHP1402, have long been used for treating anti-dementia or hypomnesia as folk medicine. AIM OF THE STUDY: It has been reported that Z. jujuba var. spinosa and C. lanceolata are effective on cognitive function with different mechanism of action. Therefore, in the present study, we evaluated the synergistic effects of Ziziphus jujuba var...
September 13, 2017: Journal of Ethnopharmacology
https://www.readbyqxmd.com/read/28911965/physiological-roles-of-cns-muscarinic-receptors-gained-from-knockout-mice
#5
REVIEW
Morgane Thomsen, Gunnar Sørensen, Ditte Dencker
Because the five muscarinic acetylcholine receptor subtypes have overlapping distributions in many CNS tissues, and because ligands with a high degree of selectivity for a given subtype long remained elusive, it has been difficult to determine the physiological functions of each receptor. Genetically engineered knockout mice, in which one or more muscarinic acetylcholine receptor subtype has been inactivated, have been instrumental in identifying muscarinic receptor functions in the CNS, at the neuronal, circuit, and behavioral level...
September 11, 2017: Neuropharmacology
https://www.readbyqxmd.com/read/28901737/melatonin-improves-cognitive-deficits-via-restoration-of-cholinergic-dysfunction-in-a-mouse-model-of-scopolamine-induced-amnesia
#6
Bai Hui Chen, Joon Ha Park, Dae Won Kim, Jinseu Park, Soo Young Choi, In Hye Kim, Jeong Hwi Cho, Tae-Kyeong Lee, Jae Chul Lee, Choong-Hyun Lee, In Koo Hwang, Young-Myeong Kim, Bing Chun Yan, Il-Jun Kang, Bich Na Shin, Yun Lyul Lee, Myoung Cheol Shin, Jun Hwi Cho, Young Joo Lee, Yong Hwan Jeon, Moo-Ho Won, Ji Hyeon Ahn
Melatonin is known to improve cognitive deficits and its functions have been studied in various disease models, including Alzheimer's disease. In this study, we investigated effects of melatonin on cognition and the cholinergic system of the septum and hippocampus in a mouse model of scopolamine-induced amnesia. Scopolamine (1 mg/kg) and melatonin (10 mg/kg) were administered intraperitoneally to mice for 2 and 4 weeks. The Morris water maze and passive avoidance tests revealed that both treatments of scopolamine significantly impaired spatial learning and memory; however, 2- and 4-week melatonin treatments significantly improved the spatial learning and memory...
September 13, 2017: ACS Chemical Neuroscience
https://www.readbyqxmd.com/read/28894302/g%C3%AE-%C3%AE-subunit-activation-promotes-dopamine-efflux-through-the-dopamine-transporter
#7
J Garcia-Olivares, T Baust, S Harris, P Hamilton, A Galli, S G Amara, G E Torres
The dopamine transporter (DAT) is an important regulator of brain dopamine (DA) homeostasis, controlling the intensity and duration of DA signaling. DAT is the target for psychostimulants-like cocaine and amphetamine-and plays an important role in neuropsychiatric disorders, including attention-deficit hyperactivity disorder and drug addiction. Thus, a thorough understanding of the mechanisms that regulate DAT function is necessary for the development of clinical interventions to treat DA-related brain disorders...
September 12, 2017: Molecular Psychiatry
https://www.readbyqxmd.com/read/28893976/teaching-an-old-drug-new-tricks-agonism-antagonism-and-biased-signaling-of-pilocarpine-through-m3-muscarinic-acetylcholine-receptor
#8
Alexey Pronin, Qiang Wang, Vladlen Z Slepak
Pilocarpine is a prototypical drug used to treat glaucoma and dry mouth and classified as either a full or partial muscarinic agonist. Here, we report several unexpected results pertaining to its interaction with muscarinic M3 receptor (M3R). We found that pilocarpine was 1,000 times less potent in stimulating mouse eye pupil constriction than muscarinic agonists oxotremorin-M (Oxo-M) or carbachol (CCh), even though all three ligands have similar Kd values for M3R. In contrast to CCh or Oxo-M, pilocarpine does not induce Ca2+ mobilization via endogenous M3R in HEK293T or mouse insulinoma MIN6 cells...
September 11, 2017: Molecular Pharmacology
https://www.readbyqxmd.com/read/28893841/endogenous-signalling-pathways-and-caged-ip3-evoke-ca-2-puffs-at-the-same-abundant-immobile-intracellular-sites
#9
Michael V Keebler, Colin W Taylor
The building blocks for intracellular Ca(2+) signals evoked by inositol 1,4,5-trisphosphate receptors (IP3Rs) are Ca(2+) puffs, transient focal increases in Ca(2+) concentration that reflect the opening of a small clusters of IP3Rs. We use total internal reflection fluorescence microscopy and automated analyses to detect Ca(2+) puffs in human embryonic kidney 293 cells evoked by photolysis of caged-IP3 or activation of endogenous muscarinic receptors with carbachol. Ca(2+) puffs evoked by carbachol initiated at an estimated 65 ± 7 sites/cell, and the sites remained immobile for many minutes...
September 11, 2017: Journal of Cell Science
https://www.readbyqxmd.com/read/28893562/positive-allosteric-modulation-of-m1-and-m4-muscarinic-receptors-as-potential-therapeutic-treatments-for-schizophrenia
#10
REVIEW
Samantha E Yohn, P Jeffrey Conn
Current antipsychotic drugs provide symptomatic relief for positive symptoms of schizophrenia, but do not offer symptom management for negative and cognitive symptoms. In addition, many patients discontinue treatment due to adverse side effects. Therefore, there is a critical need to develop more effective and safe treatment options. Although the etiology of schizophrenia is unclear, considerable data from post-mortem, neuroimaging and neuropharmacology studies support a role of the muscarinic acetylcholine (mAChRs) in the pathophysiology of schizophrenia...
September 9, 2017: Neuropharmacology
https://www.readbyqxmd.com/read/28892404/mechanisms-underlying-metabolic-disturbances-associated-with-psychosis-and-antipsychotic-drug-treatment
#11
Gavin P Reynolds, Olga O McGowan
The increase in cardiovascular disease and reduced life expectancy in schizophrenia likely relate to an increased prevalence of metabolic disturbances. Such metabolic risk factors in schizophrenia may result from both symptom-related effects and aetiological factors. However, a major contributory factor is that of treatment with antipsychotic drugs. These drugs differ in effects on body weight; the underlying mechanisms are not fully understood and may vary between drugs, but may include actions at receptors associated with the hypothalamic control of food intake...
August 1, 2017: Journal of Psychopharmacology
https://www.readbyqxmd.com/read/28890048/molecular-cellular-and-circuit-basis-of-cholinergic-modulation-of-pain
#12
Paul V Naser, Rohini Kuner
In addition to being a key component of the autonomic nervous system, acetylcholine acts as a prominent neurotransmitter and neuromodulator upon release from key groups of cholinergic projection neurons and interneurons distributed across the central nervous system. It has been more than forty years since it was discovered that cholinergic transmission profoundly modifies the perception of pain. Directly activating cholinergic receptors or extending the action of endogenous acetylcholine via pharmacological blockade of acetylcholine esterase reduces pain in rodents as well as humans; conversely, inhibition of muscarinic cholinergic receptors induces nociceptive hypersensitivity...
September 8, 2017: Neuroscience
https://www.readbyqxmd.com/read/28888822/discovery-of-novel-steroidal-histamine-h3-receptor-antagonists-inverse-agonists
#13
Istvan Ledneczki, Pál Tapolcsányi, Eszter Gábor, János Éles, István Greiner, Éva Schmidt, Zsolt Némethy, Rita Soukupné Kedves, Ottilia Balázs, Viktor Román, György Lévay, Sándor Mahó
Emerging from an HTS campaign, novel steroid-based histamine H3 receptor antagonists were identified and characterized. Structural moieties of the hit compounds were combined to improve binding affinities which resulted in compound 4 as lead molecule. During the lead optimization due to the versatile modifications of diamino steroid derivatives, several in vitro potent compounds with subnanomolar binding affinities to histamine H3 receptors were found. The unfavorable binding to rat muscarinic receptors was successfully reduced by tuning the basicity...
September 1, 2017: Bioorganic & Medicinal Chemistry Letters
https://www.readbyqxmd.com/read/28887860/regulation-of-radial-glial-process-growth-by-glutamate-via-mglur5-trpc3-and-neuregulin-erbb4
#14
Lauri M Louhivuori, Pauli M Turunen, Verna Louhivuori, Venkatram Yellapragada, Tommy Nordström, Per Uhlén, Karl E Åkerman
Radial glial cells play an essential role through their function as guides for neuronal migration during development. Disruption of metabotropic glutamate receptor 5 (mGluR5) function retards the growth of radial glial processes in vitro. Neuregulins (NRG) are activated by proteolytic cleavage and regulate (radial) glial maintenance via ErbB3/ErbB4 receptors. We show here that blocking ErbB4 disrupts radial process extension. Soluble NRG acting on ErbB4 receptors is able to promote radial process extension in particular where process elongation has been impeded by blockade of mGluR5, the nonselective cation channel canonical transient receptor potential 3 (TRPC3), or matrix metalloproteases (MMP)...
September 9, 2017: Glia
https://www.readbyqxmd.com/read/28884467/cre-expressing-neurons-in-visual-cortex-of-ntsr1-cre-gn220-mice-are-corticothalamic-and-are-depolarized-by-acetylcholine
#15
Sofie Charlotte Sundberg, Sarah Helen Lindström, Gonzalo Manuel Sanchez, Björn Granseth
The Ntsr1-Cre GN220 mouse expresses Cre-recombinase in corticothalamic (CT) neurons in neocortical layer 6. It is not known if the other major types of pyramidal neurons in this layer also express this enzyme. By electrophysiological recordings in slices and histological analysis of the uptake of retrogradely transported beads we show that Cre-positive neurons are corticothalamic and not corticocortical or cortico-claustral types. Furthermore, we show that Ntsr1-Cre-positive cells are immuno-positive for the nuclear transcription factor Forkhead box protein P2 (FoxP2)...
September 7, 2017: Journal of Comparative Neurology
https://www.readbyqxmd.com/read/28878678/verapamil-blocks-scopolamine-enhancement-effect-on-memory-consolidation-in-passive-avoidance-task-in-rats
#16
Verónica Giménez De Béjar, María Caballero Bleda, Natalija Popović, Miroljub Popović
Our recent data have indicated that scopolamine, a non-selective muscarinic receptor antagonist, improves memory consolidation, in a passive avoidance task, tested in rats. It has been found that verapamil, a phenylalkylamine class of the L-type voltage-dependent calcium channel antagonist, inhibits [3H] N-methyl scopolamine binding to M1 muscarinic receptors. However, there are no data about the effect of verapamil on memory consolidation in the passive avoidance task, in rats. The purpose of the present study was to examine the effects of verapamil (0...
2017: Frontiers in Pharmacology
https://www.readbyqxmd.com/read/28877931/prostaglandin-e2-inhibits-histamine-evoked-ca2-release-in-human-aortic-smooth-muscle-cells-through-hyperactive-camp-signalling-junctions-and-protein-kinase-a
#17
Emily J A Taylor, Evangelia Pantazaka, Kathryn L Shelley, Colin W Taylor
In human aortic smooth muscle cells (ASMC), prostaglandin E2 (PGE2) stimulates adenylyl cyclase (AC) and attenuates the increase in intracellular free Ca(2+) concentration ([Ca(2+)]i) evoked by activation of histamine H1 receptors. The mechanisms are not resolved. We show that cAMP mediates inhibition of histamine-evoked Ca(2+) signals by PGE2 Exchange proteins activated by cAMP (EPACs) were not required, but the effects were attenuated by inhibition of cAMP-dependent protein kinase (PKA). PGE2 had no effect on the Ca(2+) signals evoked by protease-activated receptors, heterologously expressed muscarinic M3 receptors, or by direct activation of inositol 1,4,5-trisphosphate (IP3) receptors by photolysis of caged IP3 The rate of Ca(2+) removal from the cytosol was unaffected by PGE2, but PGE2 attenuated histamine-evoked IP3 accumulation...
September 6, 2017: Molecular Pharmacology
https://www.readbyqxmd.com/read/28876363/dipyrone-in-association-with-atropine-inhibits-the-effect-on-gastric-emptying-induced-by-hypoglycemia-in-rats
#18
E F Collares, A M Vinagre, C B Collares-Buzato
Atropine (AT) and dipyrone (Dp) induce a delay of gastric emptying (GE) of liquids in rats by inhibiting muscarinic receptors and activating β2-adrenergic receptors, respectively. The objective of the present study was to determine the effects of pretreatment with AT and Dp, given alone or in combination, on the effect of hypoglycemia in the liquid GE in rats. Male Wistar adult rats (280-310 g) were pretreated intravenously with AT, Dp, AT plus Dp or their vehicle and then treated 30 min later with iv insulin or its vehicle (n=8-10 animals/group)...
August 31, 2017: Brazilian Journal of Medical and Biological Research, Revista Brasileira de Pesquisas Médicas e Biológicas
https://www.readbyqxmd.com/read/28875855/impurity-profile-of-bronchodilators-used-in-asthma-a-critical-review
#19
Krunal J Prajapati, Charmy Kothari
BACKGROUND: Asthma is defined as a heterogeneous disease usually characterized by chronic airway inflammation (GINA 2016) affecting almost 334 million people worldwide (Global asthma report 2014). Treatment of asthma with a long-acting bronchodilator is important because it reduces the symptoms that occur at night or in the early morning and it is very effective to use as a long term control medication for asthma by preventing asthmatic symptoms. The main objective of this review is to describe the impurity profile and force degradation studies for three major classes of bronchodilators namely β2-adrenoceptor agonists, muscarinic receptor antagonists and xanthine...
August 29, 2017: Current Drug Discovery Technologies
https://www.readbyqxmd.com/read/28864239/network-oscillatory-activity-driven-by-context-memory-processing-is-differently-regulated-by-glutamatergic-and-cholinergic-neurotransmission
#20
Adam M P Miller, Brendan J Frick, David M Smith, Jelena Radulovic, Kevin A Corcoran
Memory retrieval requires coordinated intra- and inter-regional activity in networks of brain structures. Dysfunction of these networks and memory impairment are seen in many psychiatric disorders, but relatively little is known about how memory retrieval and memory failure are represented at the level of local and regional oscillatory activity. To address this question, we measured local field potentials (LFPs) from mice as they explored a novel context, retrieved memories for contextual fear conditioning, and after administration of two amnestic agents: the NMDA receptor antagonist MK-801 and muscarinic acetylcholine receptor antagonist scopolamine (SCOP)...
August 30, 2017: Neurobiology of Learning and Memory
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