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https://www.readbyqxmd.com/read/27904901/effect-of-ticagrelor-on-endothelial-calcium-signalling-and-barrier-function
#1
Dursun Gündüz, Christian Tanislav, Klaus-Dieter Schlüter, Rainer Schulz, Christian Hamm, Muhammad Aslam
The P2Y12 receptor is a Gi-coupled receptor whose activation inhibits adenylyl cyclase and thereby reduces the concentration of intracellular cAMP. Here the hypothesis was tested whether AR-C 66096 or ticagrelor, two direct-acting and reversibly binding P2Y12 receptor antagonists, protect endothelial cell (EC) barrier function by raising intracellular cAMP in ECs. The study was carried out on primary human umbilical vein ECs (HUVECs) and human pulmonary microvascular ECs (hPMECs). AR-C66096 (10 µM) induced a 50 % increase in cAMP in ECs whereas ticagrelor (2-10 µM) had no effect...
December 1, 2016: Thrombosis and Haemostasis
https://www.readbyqxmd.com/read/27888240/topological-organisation-of-the-phosphatidylinositol-4-5-bisphosphate-phospholipase-c-resynthesis-cycle-pitps-bridge-the-er-pm-gap
#2
REVIEW
Shamshad Cockcroft, Padinjat Raghu
Phospholipase C (PLC) is a receptor-regulated enzyme that hydrolyses phosphatidylinositol 4,5-bisphosphate (PI(4,5)P2) at the plasma membrane (PM) triggering three biochemical consequences, the generation of soluble inositol 1,4,5-trisphosphate (IP3), membrane-associated diacylglycerol (DG) and the consumption of PM PI(4,5)P2 Each of these three signals triggers multiple molecular processes impacting key cellular properties. The activation of PLC also triggers a sequence of biochemical reactions, collectively referred to as the PI(4,5)P2 cycle that culminates in the resynthesis of this lipid...
December 1, 2016: Biochemical Journal
https://www.readbyqxmd.com/read/27887748/probes-for-manipulating-and-monitoring-ip3
#3
REVIEW
Akitoshi Miyamoto, Katsuhiko Mikoshiba
Inositol 1,4,5-trisphosphate (IP3) is an important second messenger produced via G-protein-coupled receptor- or receptor tyrosine kinase-mediated pathways. IP3 levels induce Ca(2+) release from the endoplasmic reticulum (ER) via IP3 receptor (IP3R) located in the ER membrane. The resultant spatiotemporal pattern of Ca(2+) signals regulates diverse cellular functions, including fertilization, gene expression, synaptic plasticity, and cell death. Therefore, monitoring and manipulating IP3 levels is important to elucidate not only the functions of IP3-mediated pathways but also the encoding mechanism of IP3R as a converter of intracellular signals from IP3 to Ca(2+)...
November 17, 2016: Cell Calcium
https://www.readbyqxmd.com/read/27856517/mglur-long-term-depression-regulates-glua2-association-with-copii-vesicles-and-exit-from-the-endoplasmic-reticulum
#4
Joseph E Pick, Latika Khatri, Matheus F Sathler, Edward B Ziff
mGluR long-term depression (mGluR-LTD) is a form of synaptic plasticity induced at excitatory synapses by metabotropic glutamate receptors (mGluRs). mGluR-LTD reduces synaptic strength and is relevant to learning and memory, autism, and sensitization to cocaine; however, the mechanism is not known. Here we show that activation of Group I mGluRs in medium spiny neurons induces trafficking of GluA2 from the endoplasmic reticulum (ER) to the synapse by enhancing GluA2 binding to essential COPII vesicle proteins, Sec23 and Sec13...
November 17, 2016: EMBO Journal
https://www.readbyqxmd.com/read/27848113/calcium-waves-in-a-grid-of-clustered-channels-with-synchronous-ip3-binding-and-unbinding
#5
M Rückl, S Rüdiger
Calcium signals in cells occur at multiple spatial scales and variable temporal duration. However, a physical explanation for transitions between long-lasting global oscillations and localized short-term elevations (puffs) of cytoplasmic Ca(2+) is still lacking. Here we introduce a phenomenological, coarse-grained model for the calcium variable, which is represented by ordinary differential equations. Due to its small number of parameters, and its simplicity, this model allows us to numerically study the interplay of multi-scale calcium concentrations with stochastic ion channel gating dynamics even in larger systems...
November 2016: European Physical Journal. E, Soft Matter
https://www.readbyqxmd.com/read/27836216/regulation-of-ip3-receptors-by-cyclic-amp
#6
REVIEW
Colin W Taylor
Ca(2+) and cAMP are ubiquitous intracellular messengers and interactions between them are commonplace. Here the effects of cAMP on inositol 1,4,5-trisphosphate receptors (IP3Rs) are briefly reviewed. All three subtypes of IP3R are phosphorylated by cAMP-dependent protein kinase (PKA). This potentiates IP3-evoked Ca(2+) release through IP3R1 and IP3R2, but probably has little effect on IP3R3. In addition, cAMP can directly sensitize all three IP3R subtypes to IP3. The high concentrations of cAMP required for this PKA-independent modulation of IP3Rs is delivered to them within signalling junctions that include type 6 adenylyl cyclase and IP3R2...
November 6, 2016: Cell Calcium
https://www.readbyqxmd.com/read/27823962/the-transient-receptor-potential-ankyrin-1-mediates-mechanical-hyperalgesia-induced-by-the-activation-of-b1-receptor-in-mice
#7
Flavia Carla Meotti, Cláudia Pinto Figueiredo, Marianne Manjavachi, João B Calixto
The kinin receptor B1 and the transient receptor potential ankyrin 1 (TRPA1) work as initiators and gatekeepers of nociception and inflammation. This study reports that the nociceptive transmission induced by activation of B1 receptor is dependent on TRPA1 ion channel. The mechanical hyperalgesia was induced by intrathecal (i.t.) injection of B1 agonist des-Arginine(9)-bradykinin (DABK) or TRPA1 agonist cinnamaldehyde and was evaluated by the withdrawal response after von Frey Hair application in the hind paw...
November 4, 2016: Biochemical Pharmacology
https://www.readbyqxmd.com/read/27788256/p2y1-receptor-signaling-contributes-to-high-salt-induced-priming-of-the-nlrp3-inflammasome-in-retinal-pigment-epithelial-cells
#8
Philipp Prager, Margrit Hollborn, Anja Steffen, Peter Wiedemann, Leon Kohen, Andreas Bringmann
BACKGROUND: Systemic hypertension is a risk factor of age-related macular degeneration (AMD), a chronic inflammatory disease. Acute hypertension is caused by increased extracellular osmolarity after intake of dietary salt (NaCl). We determined in cultured human retinal pigment epithelial (RPE) cells whether high extracellular NaCl alters the gene expression of inflammasome-associated proteins, and whether autocrine/paracrine purinergic (P2) receptor signaling contributes to the NaCl-induced NLRP3 gene expression...
2016: PloS One
https://www.readbyqxmd.com/read/27777977/ip3-receptors-regulate-vascular-smooth-muscle-contractility-and-hypertension
#9
Qingsong Lin, Guiling Zhao, Xi Fang, Xiaohong Peng, Huayuan Tang, Hong Wang, Ran Jing, Jie Liu, W Jonathan Lederer, Ju Chen, Kunfu Ouyang
Inositol 1, 4, 5-trisphosphate receptor-mediated (IP3R-mediated) calcium (Ca(2+)) release has been proposed to play an important role in regulating vascular smooth muscle cell (VSMC) contraction for decades. However, whether and how IP3R regulates blood pressure in vivo remains unclear. To address these questions, we have generated a smooth muscle-specific IP3R triple-knockout (smTKO) mouse model using a tamoxifen-inducible system. In this study, the role of IP3R-mediated Ca(2+) release in adult VSMCs on aortic vascular contractility and blood pressure was assessed following tamoxifen induction...
October 20, 2016: JCI Insight
https://www.readbyqxmd.com/read/27768902/regulation-of-proteasome-activity-by-p2y2-receptor-underlies-the-neuroprotective-effects-of-extracellular-nucleotides
#10
Laura de Diego-García, Mercedes Ramírez-Escudero, Álvaro Sebastián-Serrano, Juan Ignacio Diaz-Hernández, Jesús Pintor, José J Lucas, Miguel Díaz-Hernández
The Ubiquitin-Proteasome System (UPS) is essential for the regulation of the cellular proteostasis. Indeed, it has been postulated that an UPS dysregulation is the common mechanism that underlies several neurological disorders. Considering that extracellular nucleotides, through their selective P2Y2 receptor (P2Y2R), play a neuroprotective role in various neurological disorders that course with an UPS impairment, we wonder if this neuroprotective capacity resulted from their ability to modulate the UPS. Using a cellular model expressing two different UPS reporters, we found that the stimulation of P2Y2R by its selective agonist Up4U induced a significant reduction of UPS reporter levels...
October 18, 2016: Biochimica et Biophysica Acta
https://www.readbyqxmd.com/read/27749281/comparison-of-gating-dynamics-of-different-ip3r-channels-with-immune-algorithm-searching-for-channel-parameter-distributions
#11
Xiuhong Cai, Xiang Li, Hong Qi, Fang Wei, Jianyong Chen, Jianwei Shuai
The gating properties of the inositol 1, 4, 5-trisphosphate (IP3) receptor (IP3R) are determined by the binding and unbinding capability of Ca(2+) ions and IP3 messengers. With the patch clamp experiments, the stationary properties have been discussed for Xenopus oocyte type-1 IP3R (Oo-IP3R1), type-3 IP3R (Oo-IP3R3) and Spodoptera frugiperda IP3R (Sf-IP3R). In this paper, in order to provide insights about the relation between the observed gating characteristics and the gating parameters in different IP3Rs, we apply the immune algorithm to fit the parameters of a modified DeYoung-Keizer model...
October 17, 2016: Physical Biology
https://www.readbyqxmd.com/read/27744004/histamine-h3-receptor-activation-stimulates-calcium-mobilization-in-a-subpopulation-of-rat-striatal-neurons-in-primary-culture-but-not-in-synaptosomes
#12
Nayeli Rivera-Ramírez, Wilber Montejo-López, María-Cristina López-Méndez, Agustín Guerrero-Hernández, Anayansi Molina-Hernández, Ubaldo García-Hernández, José-Antonio Arias-Montaño
The histamine H3 receptor (H3R) is abundantly expressed in the Central Nervous System where it regulates several functions pre and postsynaptically. H3Rs couple to Gαi/o proteins and trigger or modulate several intracellular signaling pathways, including the cAMP/PKA pathway and the opening of N- and P/Q-type voltage-gated Ca(2+) channels. In transfected cells, activation of the human H3R of 445 amino acids (hH3R445) results in phospholipase C (PLC) stimulation and release of Ca(2+) from intracellular stores...
December 2016: Neurochemistry International
https://www.readbyqxmd.com/read/27743014/membrane-protein-quantity-control-at-the-endoplasmic-reticulum
#13
Ignat Printsev, Daniel Curiel, Kermit L Carraway
The canonical function of the endoplasmic reticulum-associated degradation (ERAD) system is to enforce quality control among membrane-associated proteins by targeting misfolded secreted, intra-organellar, and intramembrane proteins for degradation. However, increasing evidence suggests that ERAD additionally functions in maintaining appropriate levels of a subset of membrane-associated proteins. In this 'quantity control' capacity, ERAD responds to environmental cues to regulate the proteasomal degradation of specific ERAD substrates according to cellular need...
October 14, 2016: Journal of Membrane Biology
https://www.readbyqxmd.com/read/27721178/foeniculum-vulgare-mill-increases-cytosolic-ca-2-concentration-and-inhibits-store-operated-ca-2-entry-in-vascular-endothelial-cells
#14
A Young Han, Hui Su Lee, Geun Hee Seol
This study assessed the effects of essential oil of Foeniculum vulgare Mill. (fennel oil) and of trans-anethole, the main component of fennel oil, on extracellular Ca(2+)-induced store-operated Ca(2+) entry (SOCE) into vascular endothelial (EA) cells and their mechanisms of action. Components of fennel oil were analyzed by gas chromatography-mass spectrometry. Cytosolic Ca(2+) concentration ([Ca(2+)]c) in EA cells was determined using Fura-2 fluorescence. In the presence of extracellular Ca(2+), fennel oil significantly increased [Ca(2+)]c in EA cells; this increase was significantly inhibited by the Ca(2+) channel blockers La(3+) and nifedipine...
October 6, 2016: Biomedicine & Pharmacotherapy, Biomédecine & Pharmacothérapie
https://www.readbyqxmd.com/read/27720892/carbon-monoxide-releasing-molecule-induces-endothelial-nitric-oxide-synthase-activation-through-a-calcium-and-phosphatidylinositol-3-kinase-akt-mechanism
#15
Po-Min Yang, Yu-Ting Huang, Yu-Qi Zhang, Chia-Wen Hsieh, Being-Sun Wung
The production of nitric oxide (NO) by endothelial NO synthase (eNOS) plays a major role in maintaining vascular homeostasis. This study elucidated the potential role of carbon monoxide (CO)-releasing molecules (CORMs) in NO production and explored the underlying mechanisms in endothelial cells. We observed that 25μM CORM-2 could increase NO production and stimulate an increase in the intracellular Ca(2+) level. Furthermore, ethylene glycol-bis(β-aminoethyl ether)-N,N,N',N'-tetra acetic acid caused CORM-2-induced NO production, which was abolished by 1,2-bis(2-aminophenoxy) ethane-N,N,N',N'-tetraacetic acid tetraacetoxy-methyl ester (BAPTA-AM), indicating that intracellular Ca(2+) release plays a major role in eNOS activation...
October 5, 2016: Vascular Pharmacology
https://www.readbyqxmd.com/read/27716400/perk-regulates-gq-protein-coupled-intracellular-ca-2-dynamics-in-primary-cortical-neurons
#16
Siying Zhu, Barbara C McGrath, Yuting Bai, Xin Tang, Douglas R Cavener
PERK (EIF2AK3) is an ER-resident eIF2α kinase required for behavioral flexibility and metabotropic glutamate receptor-dependent long-term depression via its translational control. Motivated by the recent discoveries that PERK regulates Ca(2+) dynamics in insulin-secreting β-cells underlying glucose-stimulated insulin secretion, and modulates Ca(2+) signals-dependent working memory, we explored the role of PERK in regulating Gq protein-coupled Ca(2+) dynamics in pyramidal neurons. We found that acute PERK inhibition by the use of a highly specific PERK inhibitor reduced the intracellular Ca(2+) rise stimulated by the activation of acetylcholine, metabotropic glutamate and bradykinin-2 receptors in primary cortical neurons...
October 1, 2016: Molecular Brain
https://www.readbyqxmd.com/read/27683906/hypocretin-orexin-peptides-alter-spike-encoding-by-serotonergic-dorsal-raphe-neurons-through-two-distinct-mechanisms-that-increase-the-late-afterhyperpolarization
#17
Masaru Ishibashi, Iryna Gumenchuk, Kenichi Miyazaki, Takafumi Inoue, William N Ross, Christopher S Leonard
UNLABELLED: Orexins (hypocretins) are neuropeptides that regulate multiple homeostatic processes, including reward and arousal, in part by exciting serotonergic dorsal raphe neurons, the major source of forebrain serotonin. Here, using mouse brain slices, we found that, instead of simply depolarizing these neurons, orexin-A altered the spike encoding process by increasing the postspike afterhyperpolarization (AHP) via two distinct mechanisms. This orexin-enhanced AHP (oeAHP) was mediated by both OX1 and OX2 receptors, required Ca(2+) influx, reversed near EK, and decayed with two components, the faster of which resulted from enhanced SK channel activation, whereas the slower component decayed like a slow AHP (sAHP), but was not blocked by UCL2077, an antagonist of sAHPs in some neurons...
September 28, 2016: Journal of Neuroscience: the Official Journal of the Society for Neuroscience
https://www.readbyqxmd.com/read/27677282/at-the-cross-point-of-connexins-calcium-and-atp-blocking-hemichannels-inhibits-vasoconstriction-of-rat-small-mesenteric-arteries
#18
Mélissa Bol, Nan Wang, Marijke De Bock, Benjamin Wacquier, Elke Decrock, Ashish Gadicherla, Kelly Decaluwé, Bert Vanheel, Harold V van Rijen, Dmitri V Krysko, Geert Bultynck, Geneviève Dupont, Johan Van de Voorde, Luc Leybaert
AIMS: Connexins form gap-junctions (GJs) that directly connect cells, thereby coordinating vascular cell function and controlling vessel diameter and blood flow. GJs are composed of two hemichannels contributed by each of the connecting cells. Hemichannels also exist as non-junctional channels that, when open, lead to the entry/loss of ions and the escape of ATP. Here we investigated cross-talk between hemichannels and Ca(2+)/purinergic signaling in controlling blood vessel contraction...
September 27, 2016: Cardiovascular Research
https://www.readbyqxmd.com/read/27665314/role-of-subcellular-calcium-redistribution-in-regulating-apoptosis-and-autophagy-in-cadmium-exposed-primary-rat-proximal-tubular-cells
#19
Fei Liu, Zi-Fa Li, Zhen-Yong Wang, Lin Wang
Ca(2+) signaling plays a vital role in regulating apoptosis and autophagy. We previously proved that cytosolic Ca(2+) overload is involved in cadmium (Cd)-induced apoptosis in rat proximal tubular (rPT) cells, but the source of elevated cytosolic Ca(2+) concentration ([Ca(2+)]c) and the effect of potential subcellular Ca(2+) redistribution on apoptosis and autophagy remain to be elucidated. Firstly, data showed that Cd-induced elevation of [Ca(2+)]c was primarily generated intracellularly. Moreover, elevations of [Ca(2+)]c and mitochondrial Ca(2+) concentration ([Ca(2+)]mit) with depletion of endoplasmic reticulum (ER) Ca(2+) levels ([Ca(2+)]ER) were revealed in Cd-treated rPT cells, but this subcellular Ca(2+) redistribution was significantly suppressed by 2-Aminoethoxydiphenyl borate (2-APB)...
September 14, 2016: Journal of Inorganic Biochemistry
https://www.readbyqxmd.com/read/27641745/cannabinoid-signalling-inhibits-sarcoplasmic-ca-2-release-and-regulates-excitation-contraction-coupling-in-mammalian-skeletal-muscle
#20
Tamás Oláh, Dóra Bodnár, Adrienn Tóth, János Vincze, János Fodor, Barbara Reischl, Adrienn Kovács, Olga Ruzsnavszky, Beatrix Dienes, Péter Szentesi, Oliver Friedrich, László Csernoch
Marijuana was found to cause muscle weakness, but it is unknown whether it affects the muscles directly, or modulates only the motor control of the central nervous system. Although the presence of CB1 cannabinoid receptors (CB1R) - responsible for the psychoactive effects of the drug in the brain - have recently been shown in skeletal muscle, it is unclear how CB1R-mediated signalling affects the contraction and Ca²⁺ homeostasis of mammalian skeletal muscle. Here we demonstrate that in vitro CB1R activation increased muscle fatigability, decreased the Ca(2+) -sensitivity of the contractile apparatus, but did not alter the amplitude of single twitch contractions...
September 19, 2016: Journal of Physiology
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