scholarly journals High-content RNAi screening identifies the Type 1 inositol triphosphate receptor as a modifier of TDP-43 localization and neurotoxicity

2012 ◽  
Vol 21 (22) ◽  
pp. 4845-4856 ◽  
Author(s):  
Sang Hwa Kim ◽  
Lihong Zhan ◽  
Keith A. Hanson ◽  
Randal S. Tibbetts
Keyword(s):  
Inositol Triphosphate ◽  
Rnai Screening ◽  
Inositol Triphosphate Receptor

scholarly journals Desensitization of angiotensin II: effect on [Ca2+]i, inositol triphosphate, and prolactin in pituitary cells

2001 ◽  
Vol 280 (3) ◽  
pp. E462-E470 ◽  
Author(s):  
Arturo González Iglesias ◽  
Cecilia Suárez ◽  
Claudia Feierstein ◽  
Graciela Dı́az-Torga ◽  
Damasia Becu-Villalobos
Keyword(s):  
Inositol Phosphate ◽  
Prolactin Secretion ◽  
Inositol Triphosphate ◽  
Pituitary Cells ◽  
Partial Recovery ◽  
Ang Ii ◽  
Pretreated Group ◽  
Intracellular Ca ◽  
Heterologous Desensitization

Activation of pituitary angiotensin (ANG II) type 1 receptors (AT1) mobilizes intracellular Ca2+, resulting in increased prolactin secretion. We first assessed desensitization of AT1 receptors by testing ANG II-induced intracellular Ca2+ concentration ([Ca2+]i) response in rat anterior pituitary cells. A period as short as 1 min with 10−7 M ANG II was effective in producing desensitization (remaining response was 66.8 ± 2.1% of nondesensitized cells). Desensitization was a concentration-related event (EC50: 1.1 nM). Although partial recovery was obtained 15 min after removal of ANG II, full response could not be achieved even after 4 h (77.6 ± 2.4%). Experiments with 5 × 10−7 M ionomycin indicated that intracellular Ca2+ stores of desensitized cells had already recovered when desensitization was still significant. The thyrotropin-releasing hormone (TRH)-induced intracellular Ca2+ peak was attenuated in the ANG II-pretreated group. ANG II pretreatment also desensitized ANG II- and TRH-induced inositol phosphate generation (72.8 ± 3.5 and 69.6 ± 6.1%, respectively, for inositol triphosphate) and prolactin secretion (53.4 ± 2.3 and 65.1 ± 7.2%), effects independent of PKC activation. We conclude that, in pituitary cells, inositol triphosphate formation, [Ca2+]i mobilization, and prolactin release in response to ANG II undergo rapid, long-lasting, homologous and heterologous desensitization.

The inositol triphosphate receptor family

1996 ◽  
Vol 8 (1) ◽  
pp. 1-7 ◽  
Author(s):  
Suresh K. Joseph
Keyword(s):  
Inositol Triphosphate ◽  
Inositol Triphosphate Receptor ◽  
Receptor Family

scholarly journals Search for inositol triphosphate receptor.

1986 ◽  
Vol 26 (5) ◽  
pp. 229-234
Author(s):  
MASATO HIRATA
Keyword(s):  
Inositol Triphosphate ◽  
Inositol Triphosphate Receptor

Abstract 279: Inositol Triphosphate Receptor Activation Alters the Electrical Properties of Human Ventricular Myocytes

2012 ◽  
Vol 111 (suppl_1) ◽  
Author(s):  
Sergio Signore ◽  
João Ferreira-Martins ◽  
Kazuya Isobe ◽  
Ramaswamy Kannappan ◽  
Andrea Sorrentino ◽  
...  
Keyword(s):  
Electrical Properties ◽  
Ventricular Myocytes ◽  
Receptor Activation ◽  
Resting Potential ◽  
Inositol Triphosphate ◽  
Receptor Agonists ◽  
Protein Receptor ◽  
Inositol Triphosphate Receptor ◽  
Human And Mouse

The recognition that ryanodine receptor (RyR) dysfunction is associated to arrhythmogenic diseases raises the possibility that alternative Ca2+ release channels alter the electrical properties of ventricular myocytes. The aim of this study was to determine whether inositol triphosphate receptor (IP3R)-mediated Ca2+ mobilization modulates Ca2+ cycling and electrical behavior in LV myocytes. Cells were obtained from human and mouse hearts and the expression and function of IP3Rs were evaluated. IP3Rs were identified in isolated myocytes by immunocytochemistry and Western blotting. In field-stimulated cells, IP3R activation via Gq-protein receptor agonists (ET-1, ATP) or enhancer of ligand affinity (thimerosal) increased diastolic Ca2+ and transient amplitude by 11% and 44%, respectively. Additionally, extra-systolic Ca2+ release and sustained Ca2+ elevations were detected. These effects were prevented by inhibition of IP3 production or by IP3R blockade. Importantly, myocytes obtained from mice infected in vivo with small hairpin RNA (shRNA) targeting IP3R type 2, failed to respond to Gq-protein receptor agonists. In patch-clamped human and mouse cells, changes in Ca2+ transient properties following IP3R activation were accompanied by a decrease in resting potential, action potential (AP) prolongation, and emergence of arrhythmic events. In mouse cardiomyocytes, assessment of excitation-contraction coupling gain and blockade of RyR channels under IP3R stimulation, excluded the contribution of RyRs to the effects induced by IP3R activation. In voltage-clamped cells, IP3R agonists promoted transient inward currents at the membrane potential of -70 mV and increased a nickel-sensitive current in the range of potentials corresponding to forward mode operation of the Na-Ca exchanger. To establish whether enhanced Ca2+ load was responsible for the altered electrical properties under IP3R activation, conditions buffering cytosolic Ca2+ levels were employed. Under these circumstances, IPR stimulation failed to prolong the AP and to induce arrhythmias. In conclusions, our observations demonstrate that Ca2+ mobilization via IP3Rs directly alters the electrical properties of human and rodent myocytes.

scholarly journals Glucocorticoid and mineralocorticoid regulation of angiotensin II type 1 receptor binding and inositol triphosphate formation in WB cells

1999 ◽  
Vol 162 (3) ◽  
pp. 381-391 ◽  
Author(s):  
SG Shelat ◽  
LM Flanagan-Cato ◽  
SJ Fluharty
Keyword(s):  
Angiotensin Ii ◽  
Cell Line ◽  
At1 Receptor ◽  
Inositol Triphosphate ◽  
Epithelial Cell Line ◽  
Salt Appetite ◽  
Pressor Responses ◽  
The Brain

Mineralocorticoids, glucocorticoids, and angiotensin II (AngII) act cooperatively to maintain body fluid homeostasis. Mineralocorticoids, such as aldosterone and deoxycorticosterone-acetate (DOCA), function synergistically with AngII in the brain to increase salt appetite and blood pressure. In addition, glucocorticoids increase AngII-induced drinking and pressor responses and may also facilitate the actions of aldosterone on salt appetite. The AngII Type 1 (AT1) receptor mediates many of the physiological and behavioral actions of AngII. This receptor is coupled to the G-protein Gq, which mediates AngII-induced inositol triphosphate (IP3) formation. The WB cell line, a liver epithelial cell line that expresses the AT1 receptor, was used to examine the cellular basis of glucocorticoid and mineralocorticoid regulation of AT1 function. In this study corticosterone and dexamethasone treatments increased the number of AT1 receptors by activating the glucocorticoid receptor (GR). This increase in AT1 binding resulted in enhanced AngII-stimulated IP3 formation. However, only supraphysiological doses of aldosterone or DOCA increased AT1 binding, and this effect also was mediated by GR activation. Furthermore, despite evidence that mineralocorticoids and glucocorticoids function together to increase AngII-stimulated actions in vivo, aldosterone and dexamethasone did not act synergistically to affect AT1 binding, Gq expression, or IP3 formation. These results indicate that GR activation, and the subsequent increases in AT1 binding and in AngII-stimulated IP3 formation, may represent a cellular mechanism underlying the synergy between adrenal steroids and AngII.

Hypoxia-induced modification of the inositol triphosphate receptor in neuronal nuclei of newborn piglets: Role of nitric oxide

2003 ◽  
Vol 74 (2) ◽  
pp. 333-338 ◽  
Author(s):  
Om Prakash Mishra ◽  
Imaran Qayyum ◽  
Maria Delivoria-Papadopoulos
Keyword(s):  
Nitric Oxide ◽  
Inositol Triphosphate ◽  
Neuronal Nuclei ◽  
Newborn Piglets ◽  
Inositol Triphosphate Receptor

scholarly journals Taste dysfunction in BTBR mice due to a mutation of Itpr3, the inositol triphosphate receptor 3 gene

2013 ◽  
Vol 45 (18) ◽  
pp. 834-855 ◽  
Author(s):  
Michael G. Tordoff ◽  
Hillary T. Ellis
Keyword(s):  
Congenic Strain ◽  
Genetic Basis ◽  
Spontaneous Mutation ◽  
G Protein Coupled Receptors ◽  
Chromosome 17 ◽  
Inositol Triphosphate ◽  
Inositol Triphosphate Receptor ◽  
Congenic Region ◽  
Taste Dysfunction ◽  
G Protein Coupled

The BTBR T+ tf/J (BTBR) mouse strain is indifferent to exemplars of sweet, Polycose, umami, bitter, and calcium tastes, which share in common transduction by G protein-coupled receptors (GPCRs). To investigate the genetic basis for this taste dysfunction, we screened 610 BTBR × NZW/LacJ F2 hybrids, identified a potent QTL on chromosome 17, and isolated this in a congenic strain. Mice carrying the BTBR/BTBR haplotype in the 0.8-Mb (21-gene) congenic region were indifferent to sweet, Polycose, umami, bitter, and calcium tastes. To assess the contribution of a likely causative culprit, Itpr3, the inositol triphosphate receptor 3 gene, we produced and tested Itpr3 knockout mice. These were also indifferent to GPCR-mediated taste compounds. Sequencing the BTBR form of Itpr3 revealed a unique 12 bp deletion in Exon 23 (Chr 17: 27238069; Build 37). We conclude that a spontaneous mutation of Itpr3 in a progenitor of the BTBR strain produced a heretofore unrecognized dysfunction of GPCR-mediated taste transduction.

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