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https://www.readbyqxmd.com/read/28413263/intensified-microwave-assisted-n-acylation-procedure-synthesis-and-activity-evaluation-of-trpc3-channel-agonists-with-a-1-3-dihydro-2h-benzo-d-imidazol-2-one-core
#1
Gema Guedes de la Cruz, Barbora Svobodova, Michaela Lichtenegger, Oleksandra Tiapko, Klaus Groschner, Toma Glasnov
Upon controlled microwave heating and using cyanuric chloride as a coupling reagent, an efficient amidation procedure for the synthesis of 1,3-dihydro-2H-benzo[d]imidazol-2-one-based agonists of TRPC3/6 ion channels has been developed. Compared to the few conventional protocols, a drastic reduction in processing time from ca. 2 days down to 10 minutes was achieved accompanied by significantly improved product yields. The robustness of the method was confirmed by 18 additional examples including aromatic, aliphatic, and heterocyclic amines and acids...
April 2017: Synlett: Accounts and Rapid Communications in Synthetic Organic Chemistry
https://www.readbyqxmd.com/read/28395930/acetylcholine-attenuated-tnf-%C3%AE-induced-intracellular-ca-2-overload-by-inhibiting-the-formation-of-the-ncx1-trpc3-ip3r1-complex-in-human-umbilical-vein-endothelial-cells
#2
Ming Zhao, Hang-Huan Jia, Long-Zhu Liu, Xue-Yuan Bi, Man Xu, Xiao-Jiang Yu, Xi He, Wei-Jin Zang
The endoplasmic reticulum (ER) forms discrete junctions with the plasma membrane (PM) that play a critical role in the regulation of Ca(2+) signaling during cellular bioenergetics, apoptosis and autophagy. We have previously confirmed that acetylcholine can inhibit ER stress and apoptosis after inflammatory injury. However, limited research has focused on the effects of acetylcholine on ER-PM junctions. In this work, we evaluated the structure and function of the supramolecular sodium-calcium exchanger 1 (NCX1)-transient receptor potential canonical 3 (TRPC3)-inositol 1,4,5-trisphosphate receptor 1 (IP3R1) complex, which is involved in regulating Ca(2+) homeostasis during inflammatory injury...
April 7, 2017: Journal of Molecular and Cellular Cardiology
https://www.readbyqxmd.com/read/28395140/pyrazolopyrimidines-as-potent-stimulators-for-transient-receptor-potential-canonical-3-6-7-channels
#3
Chunrong Qu, Mingmin Ding, Yingmin Zhu, Yungang Lu, Juan Du, Melissa R Miller, Jinbin Tian, Jinmei Zhu, Jian Xu, Meng Wen, Aga Er-Bu, Jule Wang, Yuling Xiao, Meng Wu, Owen B McManus, Min Li, Jilin Wu, Huai-Rong Luo, Zheng-Yu Cao, Bing Shen, Hongbo Wang, Michael X Zhu, Xuechuan Hong
Transient receptor potential canonical 3/6/7 (TRPC3/6/7) are highly homologous receptor-operated non-selective cation channels. Despite their physiological significance, very few selective and potent agonists are available for functional examination of these channels. Using a cell-based high throughput screening approach, a lead compound with the pyrazolopyrimidine skeleton was identified as a TRPC6 agonist. Synthetic schemes for the lead and its analogs were established and structural-activity relationship studies were carried out...
April 10, 2017: Journal of Medicinal Chemistry
https://www.readbyqxmd.com/read/28392759/calcium-dependent-and-synapsin-dependent-pathways-for-the-presynaptic-actions-of-bdnf
#4
Qing Cheng, Sang-Ho Song, George J Augustine
We used cultured hippocampal neurons to determine the signaling pathways mediating brain-derived neurotrophic factor (BDNF) regulation of spontaneous glutamate and GABA release. BDNF treatment elevated calcium concentration in presynaptic terminals; this calcium signal reached a peak within 1 min and declined in the sustained presence of BDNF. This BDNF-induced transient rise in presynaptic calcium was reduced by SKF96365, indicating that BDNF causes presynaptic calcium influx via TRPC channels. BDNF treatment increased the frequency of miniature excitatory postsynaptic currents (mEPSCs)...
2017: Frontiers in Cellular Neuroscience
https://www.readbyqxmd.com/read/28367116/microglial-intracellular-ca-2-signaling-in-synaptic-development-and-its-alterations-in-neurodevelopmental-disorders
#5
REVIEW
Yoshito Mizoguchi, Akira Monji
Autism spectrum disorders (ASDs) are neurodevelopmental disorders characterized by deficits in social interaction, difficulties with language and repetitive/restricted behaviors. Microglia are resident innate immune cells which release many factors including proinflammatory cytokines, nitric oxide (NO) and brain-derived neurotrophic factor (BDNF) when they are activated in response to immunological stimuli. Recent in vivo imaging has shown that microglia sculpt and refine the synaptic circuitry by removing excess and unwanted synapses and be involved in the development of neural circuits or synaptic plasticity thereby maintaining the brain homeostasis...
2017: Frontiers in Cellular Neuroscience
https://www.readbyqxmd.com/read/28325835/picomolar-selective-and-subtype-specific-small-molecule-inhibition-of-trpc1-4-5-channels
#6
Hussein N Rubaiy, Melanie J Ludlow, Matthias Henrot, Hannah J Gaunt, Katarina Miteva, Sin Yin Cheung, Yasuyuki Tanahashi, Nurasyikin Hamzah, Katie E Musialowski, Nicola M Blythe, Hollie L Appleby, Marc A Bailey, Lynn McKeown, Roger Taylor, Richard Foster, Herbert Waldmann, Peter Nussbaumer, Mathias Christmann, Robin S Bon, Katsuhiko Muraki, David J Beech
The concentration of free cytosolic Ca(2+) and the voltage across the plasma membrane are major determinants of cell function. Ca(2+)-permeable non-selective cationic channels are known to regulate these parameters but understanding of these channels remains inadequate. Here we focus on Transient Receptor Potential Canonical 4 and 5 proteins (TRPC4 and TRPC5) which assemble as homomers or heteromerize with TRPC1 to form Ca(2+)-permeable non-selective cationic channels in many mammalian cell types. Multiple roles have been suggested including in epilepsy, innate fear, pain and cardiac remodeling but limitations in tools to probe these channels have restricted progress...
March 21, 2017: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/28314576/trpc6-and-kidney-disease-sclerosing-more-than-just-glomeruli
#7
Johannes Schlondorff
Fibrosis is a common response to injury but can also perpetuate tissue dysfunction. Transient receptor potential C6 (TRPC6) is implicated in cardiac and skin healing via regulation of myofibroblast differentiation. Wu et al. now demonstrate a role for TRPC6 in renal fibrosis, via a mechanism that also relies on TRPC3 and is antagonized by soluble klotho. Modulation of TRPC3/6 activity may provide a means of dampening the fibrotic response involved in chronic kidney disease progression.
April 2017: Kidney International
https://www.readbyqxmd.com/read/28292887/orai-and-trpc-channel-characterization-in-fc%C3%AE%C2%B5ri-mediated-calcium-signaling-and-mediator-secretion-in-human-mast-cells
#8
Hannah E Wajdner, Jasmine Farrington, Claire Barnard, Peter T Peachell, Christine G Schnackenberg, Joseph P Marino, Xiaoping Xu, Karen Affleck, Malcolm Begg, Elizabeth P Seward
Inappropriate activation of mast cells via the FcεRI receptor leads to the release of inflammatory mediators and symptoms of allergic disease. Calcium influx is a critical regulator of mast cell signaling and is required for exocytosis of preformed mediators and for synthesis of eicosanoids, cytokines and chemokines. Studies in rodent and human mast cells have identified Orai calcium channels as key contributors to FcεRI-initiated mediator release. However, until now the role of TRPC calcium channels in FcεRI-mediated human mast cell signaling has not been published...
March 2017: Physiological Reports
https://www.readbyqxmd.com/read/28274093/canonical-transient-receptor-potential-channels-and-their-link-with-cardio-cerebro-vascular-diseases
#9
REVIEW
Xiong Xiao, Hui-Xia Liu, Kuo Shen, Wei Cao, Xiao-Qiang Li
The canonical transient receptor potential channels (TRPCs) constitute a series of nonselective cation channels with variable degrees of Ca²⁺ selectivity. TRPCs consist of seven mammalian members, TRPC1, TRPC2, TRPC3, TRPC4, TRPC5, TRPC6, and TRPC7, which are further divided into four subtypes, TRPC1, TRPC2, TRPC4/5, and TRPC3/6/7. These channels take charge of various essential cell functions such as contraction, relaxation, proliferation, and dysfunction. This review, organized into seven main sections, will provide an overview of current knowledge about the underlying pathogenesis of TRPCs in cardio/cerebrovascular diseases, including hypertension, pulmonary arterial hypertension, cardiac hypertrophy, atherosclerosis, arrhythmia, and cerebrovascular ischemia reperfusion injury...
March 10, 2017: Biomolecules & Therapeutics
https://www.readbyqxmd.com/read/28242818/characterization-of-flow-regulated-cortical-collecting-duct-endothelin-1-production
#10
Nirupama Ramkumar, Yang Gao, Donald E Kohan
Collecting duct (CD) endothelin-1 (ET-1) is an autocrine inhibitor of Na(+) and water reabsorption. Salt or water loading increases CD ET-1 production; this is likely due, at least in part, to increased tubule fluid flow. The mechanisms by which flow stimulates CD ET-1 production are incompletely understood. In particular, flow induction of cortical CD (CCD) and inner medullary CD (IMCD) ET-1 synthesis may occur via different mechanisms. Since flow-mediated ET-1 production in IMCD has been more extensively characterized than in the CCD, this study was undertaken to further examine putative signaling pathways involved in flow-stimulated CCD ET-1 production...
February 2017: Physiological Reports
https://www.readbyqxmd.com/read/28237334/functional-involvement-of-protein-kinase-c-rho-kinase-and-trpc3-decreases-while-plc-increases-with-advancement-of-pregnancy-in-mediating-oxytocin-induced-myometrial-contractions-in-water-buffaloes-bubalus-bubalis
#11
Abhishek Sharma, Udayraj P Nakade, Soumen Choudhury, Satish Kumar Garg
Present study unravels the involvement of different calcium signaling pathways in oxytocin-induced contractions in myometrium of non-pregnant and pregnant buffaloes during early and mid-pregnancy stages. Uteri of pregnant animals were more sensitive than of non-pregnant buffaloes. Phasic contractions and frequency of contraction significantly increased with advancement of pregnancy, while tonic contractions non-significantly and amplitude significantly decreased from six months pregnancy onward. Oxytocin produced concentration-dependent-contraction on isolated myometrial strips of pregnant and non-pregnant buffaloes and the dose response curves (DRCs) of oxytocin were significantly (P < 0...
April 1, 2017: Theriogenology
https://www.readbyqxmd.com/read/28223224/transient-receptor-potential-canonical-type-3-channels-interactions-role-and-relevance-a-vascular-focus
#12
REVIEW
T H Grayson, Timothy V Murphy, Shaun L Sandow
Transient receptor potential canonical type 3 channels (TRPC3) are expressed in neural, cardiac, respiratory and vascular tissues, with both similarities and differences between human and animal models for the same cell types. In common with all members of the six subfamilies of TRP channels, TRPC3 are non-voltage gated, non-selective cation channels that are mainly permeated by Ca(2+), and have distinct molecular, biophysical, anatomical and functional properties. TRP channels are present in excitable and non-excitable cells where they sense and respond to a wide variety of physical and chemical stimuli...
February 14, 2017: Pharmacology & Therapeutics
https://www.readbyqxmd.com/read/28217875/mechanisms-of-pruritogen-induced-activation-of-itch-nerves-in-isolated-mouse-skin
#13
F Ru, H Sun, D Jurcakova, R A Herbstsomer, J Meixong, X Dong, B J Undem
Chloroquine (CQ) and histamine are pruritogens commonly used to study itch in the mouse. A novel skin-nerve preparation was used to evaluate chloroquine (CQ)- and histamine- induced activation of afferent nerves in the dorsal thoracic skin of the mouse. All CQ sensitive nerves were C-fibres, and were also sensitive to histamine. The response to CQ, but not histamine, was largely absent in mrgpr cluster Δ -/- mice supporting the hypothesis that CQ evokes itch largely via stimulation of MrgprA3 receptors. The CQ-induced action potential discharge was largely absent in phospholipase Cβ3 knockout animals...
February 19, 2017: Journal of Physiology
https://www.readbyqxmd.com/read/28186192/reduced-necrosis-and-content-of-apoptotic-m1-macrophages-in-advanced-atherosclerotic-plaques-of-mice-with-macrophage-specific-loss-of-trpc3
#14
Sumeet Solanki, Prabhatchandra R Dube, Lutz Birnbaumer, Guillermo Vazquez
In previous work we reported that ApoeKO mice transplanted with bone marrow cells deficient in the Transient Receptor Potential Canonical 3 (TRPC3) channel have reduced necrosis and number of apoptotic macrophages in advanced atherosclerotic plaques. Also, in vitro studies with polarized macrophages derived from mice with macrophage-specific loss of TRPC3 showed that M1, but not M2 macrophages, deficient in Trpc3 are less susceptible to ER stress-induced apoptosis than Trpc3 expressing cells. The questions remained (a) whether the plaque phenotype in transplanted mice resulted from a genuine effect of Trpc3 on macrophages, and (b) whether the reduced necrosis and macrophage apoptosis in plaques of these mice was a manifestation of the selective effect of TRPC3 on apoptosis of M1 macrophages previously observed in vitro...
February 10, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28181498/arrestin-biased-at1r-agonism-induces-acute-catecholamine-secretion-through-trpc3-coupling
#15
Chun-Hua Liu, Zheng Gong, Zong-Lai Liang, Zhi-Xin Liu, Fan Yang, Yu-Jing Sun, Ming-Liang Ma, Yi-Jing Wang, Chao-Ran Ji, Yu-Hong Wang, Mei-Jie Wang, Fu-Ai Cui, Amy Lin, Wen-Shuai Zheng, Dong-Fang He, Chang-Xiu Qu, Peng Xiao, Chuan-Yong Liu, Alex R B Thomsen, Thomas Joseph Cahill, Alem W Kahsai, Fan Yi, Kun-Hong Xiao, Tian Xue, Zhuan Zhou, Xiao Yu, Jin-Peng Sun
Acute hormone secretion triggered by G protein-coupled receptor (GPCR) activation underlies many fundamental physiological processes. GPCR signalling is negatively regulated by β-arrestins, adaptor molecules that also activate different intracellular signalling pathways. Here we reveal that TRV120027, a β-arrestin-1-biased agonist of the angiotensin II receptor type 1 (AT1R), stimulates acute catecholamine secretion through coupling with the transient receptor potential cation channel subfamily C 3 (TRPC3)...
February 9, 2017: Nature Communications
https://www.readbyqxmd.com/read/28124739/the-regulation-of-transient-receptor-potential-canonical-4-trpc4-channel-by-phosphodiesterase-5-inhibitor-via-the-cyclic-guanosine-3-5-monophosphate
#16
Jinhong Wie, SeungJoo Jeong, Misun Kwak, Jongyun Myeong, MeeRee Chae, Jong Kwan Park, Sung Won Lee, Insuk So
The transient receptor potential (TRP) protein superfamily consists of a diverse group of cation channels that bear structural similarities to the fruit fly Drosophila TRP. The TRP superfamily is distinct from other groups of ion channels in displaying a large diversity in ion selectivity, modes of activation, and physiological functions. Classical TRP (transient receptor potential canonical (TRPC)) channels are activated by stimulation of Gq-PLC-coupled receptors and modulated by phosphorylation. The cyclic guanosine monophosphate (cGMP)-PKG pathway is involved in the regulation of TRPC3 and TRPC6 channels...
January 26, 2017: Pflügers Archiv: European Journal of Physiology
https://www.readbyqxmd.com/read/28105583/trpc3-participates-in-angiotensin-ii-type-1-receptor-dependent-stress-induced-slow-increase-in-intracellular-ca-2-concentration-in-mouse-cardiomyocytes
#17
Yohei Yamaguchi, Gentaro Iribe, Toshiyuki Kaneko, Ken Takahashi, Takuro Numaga-Tomita, Motohiro Nishida, Lutz Birnbaumer, Keiji Naruse
When a cardiac muscle is held in a stretched position, its [Ca(2+)] transient increases slowly over several minutes in a process known as stress-induced slow increase in intracellular Ca(2+) concentration ([Ca(2+)]i) (SSC). Transient receptor potential canonical (TRPC) 3 forms a non-selective cation channel regulated by the angiotensin II type 1 receptor (AT1R). In this study, we investigated the role of TRPC3 in the SSC. Isolated mouse ventricular myocytes were electrically stimulated and subjected to sustained stretch...
January 19, 2017: Journal of Physiological Sciences: JPS
https://www.readbyqxmd.com/read/28051144/deep-transcriptomic-profiling-of-m1-macrophages-lacking-trpc3
#18
Sivarajan Kumarasamy, Sumeet Solanki, Oluwatomisin T Atolagbe, Bina Joe, Lutz Birnbaumer, Guillermo Vazquez
In previous studies using mice with macrophage-specific loss of TRPC3 we found a significant, selective effect of TRPC3 on the biology of M1, or inflammatory macrophages. Whereas activation of some components of the unfolded protein response and the pro-apoptotic mediators CamkII and Stat1 was impaired in Trpc3-deficient M1 cells, gathering insight about other molecular signatures within macrophages that might be affected by Trpc3 expression requires an alternative approach. In the present study we conducted RNA-seq analysis to interrogate the transcriptome of M1 macrophages derived from mice with macrophage-specific loss of TRPC3 and their littermate controls...
January 4, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28034747/inhibition-of-trpc3-downregulates-airway-hyperresponsiveness-remodeling-of-ova-sensitized-mouse
#19
Lingwei Wang, Jie Li, Jian Zhang, Qi He, Xuanwen Weng, Yanmei Huang, Minjie Guan, Chen Qiu
Airway hyperresponsiveness (AHR), airway remodeling and inflammation are the fundamental pathological alterations that occur in asthma. Transient receptor potential canonical 3 (TRPC3) has been implicated in diverse functions of airway smooth muscle cells (ASMCs) in asthma. However, the underlying mechanisms remain incompletely understood. We investigated the mRNA and protein expression of TRPC3 in ASMCs from normal and OVA-sensitized mouse. And the effects of inhibition or knockdown of TRPC3 with Ethyl-1- (4- (2,3,3-trichloroacrylamide) phenyl) -5 - (trifluoromethyl) -1H -pyrazole -4-carboxylate (Pyr3) and lentiviral shRNA on OVA-sensitized mouse AHR, airway remodeling, circulating inflammatory cytokines, cell proliferation and migration...
December 26, 2016: Biochemical and Biophysical Research Communications
https://www.readbyqxmd.com/read/28018223/pharmacological-characterization-of-the-native-store-operated-calcium-channels-of-cortical-neurons-from-embryonic-mouse-brain
#20
Sylvain Chauvet, Louis Jarvis, Mireille Chevallet, Niroj Shrestha, Klaus Groschner, Alexandre Bouron
In the murine brain, the first post-mitotic cortical neurons formed during embryogenesis express store-operated channels (SOCs) sensitive to Pyr3, initially proposed as a blocker of the transient receptor potential channel of C type 3 (TRPC3 channel). However, Pyr3 does not discriminate between Orai and TRPC3 channels, questioning the contribution of TRPC3 in SOCs. This study was undertaken to clarify the molecular identity and the pharmacological profile of native SOCs from E13 cortical neurons. The mRNA expression of STIM1-2 and Orai1-3 was assessed by quantitative reverse transcription polymerase chain reaction...
2016: Frontiers in Pharmacology
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