Browse
Submit Data
Databases
API
Help

Dataset Information

0 Views

0 Connections

0 Citations

0 Reanalyses

0 Downloads

Omics score: 0

Collagen stimulates [3H]inositol trisphosphate formation in indomethacin-treated human platelets.

ABSTRACT: The present study investigates the pathway of metabolism of inositol phospholipids in human platelets exposed to collagen. Platelet activation by collagen was preceded by a lag phase usually lasting 10-20 s. Formation of [3H]inositol trisphosphate (IP3) was not observed during this period, but occurred in parallel with the onset of aggregation, release of ATP and phosphorylation of a 20 000 Da and a 40 000 Da protein. Indomethacin treatment partially inhibited all of these responses. Aggregation and ATP release, but not IP3 formation, were further inhibited in indomethacin-treated platelets loaded with the fluorescent Ca2+ indicator, quin2. Under these conditions there was no detectable mobilization of Ca2+. These results demonstrate that activation of platelets by collagen is associated with rapid hydrolysis of polyphosphoinositides by phospholipase C, thereby producing IP3. This observation is discussed in relation to IP3 as a possible Ca2+-mobilizing agent.

SUBMITTER: Watson SP

PROVIDER: S-EPMC1144783 | biostudies-other | 1985 Mar

REPOSITORIES: biostudies-other

ACCESS DATA

Json Xml

Similar Datasets

Formation and metabolism of inositol 1,4,5-trisphosphate in human platelets.

Project description:1. myo-[3H]Inositol 1,4,5-trisphosphate [Ins(1,4,5)P3], when added to lysed platelets, was rapidly converted into [3H]inositol 1,3,4,5-tetrakisphosphate [Ins(1,3,4,5)P4], which was in turn converted into [3H]inositol 1,3,4-trisphosphate [Ins(1,3,4)P3]. This result demonstrates that platelets have the same metabolic pathways for interconversion of inositol polyphosphates that are found in other cells. 2. Labelling of platelets with [32P]Pi, followed by h.p.l.c., was used to measure thrombin-induced changes in the three inositol polyphosphates. Interfering compounds were removed by a combination of enzymic and non-enzymic techniques. 3. Ins(1,4,5)P3 was formed rapidly, and reached a maximum at about 4 s. It was also rapidly degraded, and was no longer detectable after 30-60 s. 4. Formation of Ins(1,3,4,5)P4 was almost as rapid as that of Ins(1,4,5)P3, and it remained detectable for a longer time. 5. Ins(1,3,4)P3 was formed after an initial lag, and this isomer reached its maximum, which was 10-fold higher than that of Ins(1,4,5)P3, at 30 s. 6. Comparison of the intracellular Ca2+ concentration as measured with fura-2 indicates that agents other than Ins(1,4,5)P3 are responsible for the sustained maintenance of a high concentration of intracellular Ca2+. It is proposed that either Ins(1,3,4)P3 or Ins(1,3,4,5)P4 may also be Ca2+-mobilizing agents.

| S-EPMC1148246 | biostudies-other

RANTES stimulates Ca2+ mobilization and inositol trisphosphate (IP3) formation in cells transfected with G protein-coupled receptor 75.

Project description:BACKGROUND AND PURPOSE: RANTES is an inflammatory chemokine with a critical role in T-lymphocyte activation and proliferation. Its effects are mediated through G protein-coupled heptahelical receptors (GPCRs). We show for the first time that RANTES activates the orphan G protein-coupled receptor 75 (GPR75). EXPERIMENTAL APPROACH: To identify a ligand for GPR75 we have used three different and independent methods, namely luciferase assay, bioluminescence assay and IP3 accumulation assay. KEY RESULTS: Treatment of cells expressing GPR75 with subnanomolar concentrations of RANTES led to stimulation of the luciferase activity in a reporter-gene assay, an increase in inositol trisphosphate, and intracellular Ca2+. The latter effect was blocked by the phospholipase-C inhibitor (PLC) U73122 indicating that Gq proteins mediate GPR75 signaling. RANTES enhanced the phosphorylation of AKT and mitogen-activated protein kinase (MAPK) in GPR75-transfected cells and this effect was blocked by the PLC inhibitor U73122 and the phosphatidylinositol 3-kinase (PI3K) inhibitor, wortmannin. The hippocampal cell line HT22, which expresses GPR75 endogenously, but not the other known RANTES receptors, was used to study the effects of RANTES and GPR75 on neuronal survival. Treatment of HT22 cells with RANTES significantly reduced the neurotoxicity of amyloid-beta peptides, by activating PLC and PI3K. CONCLUSIONS AND IMPLICATIONS: This demonstrate clearly and undoubtedly the ability of RANTES to act on GPR75. Defects in the RANTES/GPR75-signaling pathway may contribute to neuroinflammatory and neurodegenerative processes as observed in Alzheimer's disease.

| S-EPMC2014681 | biostudies-literature

Light stimulates the rapid formation of inositol trisphosphate in squid retinas.

Project description:To test the hypothesis that inositol trisphosphate (InsP3) mediates adaptation and excitation in invertebrate photoreceptors, we measured its formation on a rapid time scale in squid retinas. For squid, excitation and adaption occurs within 0.1 and 1-2 s respectively. We could detect an elevation in InsP3 within 200 ms of a bright flash. This increase is about 240% over dark basal levels and is maintained for at least 2 min after a flash. The increase probably occurs in the photoreceptors, which are the only neurons in squid retinas. Analysis by h.p.l.c. indicates that the light-regulated isomer is Ins(1,4,5)P3, which is formed by the hydrolysis of phosphatidylinositol bisphosphate (PtdInsP2).

| S-EPMC1147511 | biostudies-other

Inositol Trisphosphate Receptor Mediated Ca2+ Signalling Stimulates Mitochondrial Function and Gene Expression in Core Myopathy Patients [Human arrays]

Project description:Elevated inositol trisphosphate receptor (IP3R) levels have been previously reported in skeletal muscle myotubes derived from patients with ryanodine receptor 1 (RyR1) mutation related core myopathies. However, the functional relevance and the relationship of IP3R mediated Ca2+ signalling with the pathophysiology of the disease is unclear. It has also been suggested that mitochondrial dysfunction underlies the development of central and diffuse multi-mini-cores, devoid of mitochondrial activity, a key pathological consequence of RyR1 mutations. Here we used muscle biopsies of central core and multi-minicore disease patients with RyR1 mutations, as well as cellular and in vivo mouse models of the disease to characterise whole genome and mitochondrial gene expression to assess if remodeling of skeletal muscle following loss of functional RyR1 mediates bioenergetic adaptation.

2020-09-15 | GSE103854 | GEO

Inositol Trisphosphate Receptor Mediated Ca2+ Signalling Stimulates Mitochondrial Function and Gene Expression in Core Myopathy Patients

Project description:This SuperSeries is composed of the SubSeries listed below.

2020-09-15 | GSE103855 | GEO

Inositol 1,4,5-trisphosphate Receptor Mutations associated with Human Disease.

Project description:Calcium release into the cytosol via the inositol 1,4,5-trisphosphate receptor (IP3R) calcium channel is important for a variety of cellular processes. As a result, impairment or inhibition of this release can result in disease. Recently, mutations in all four domains of the IP3R have been suggested to cause diseases such as ataxia, cancer, and anhidrosis; however, most of these mutations have not been functionally characterized. In this review we summarize the reported mutations, as well as the associated symptoms. Additionally, we use clues from transgenic animals, receptor stoichiometry, and domain location of mutations to speculate on the effects of individual mutations on receptor structure and function and the overall mechanism of disease.

| S-EPMC6128530 | biostudies-literature

Inositol trisphosphate receptor-mediated Ca2+ signalling stimulates mitochondrial function and gene expression in core myopathy patients.

Project description:Core myopathies are a group of childhood muscle disorders caused by mutations of the ryanodine receptor (RyR1), the Ca2+ release channel of the sarcoplasmic reticulum. These mutations have previously been associated with elevated inositol trisphosphate receptor (IP3R) levels in skeletal muscle myotubes derived from patients. However, the functional relevance and the relationship of IP3R mediated Ca2+ signalling with the pathophysiology of the disease is unclear. It has also been suggested that mitochondrial dysfunction underlies the development of central and diffuse multi-mini-cores, devoid of mitochondrial activity, which is a key pathological consequence of RyR1 mutations. Here we used muscle biopsies of central core and multi-minicore disease patients with RyR1 mutations, as well as cellular and in vivo mouse models of the disease to characterize global cellular and mitochondrial Ca2+ signalling, mitochondrial function and gene expression associated with the disease. We show that RyR1 mutations that lead to the depletion of the channel are associated with increased IP3-mediated nuclear and mitochondrial Ca2+ signals and increased mitochondrial activity. Moreover, western blot and microarray analysis indicated enhanced mitochondrial biogenesis at the transcriptional and protein levels and was reflected in increased mitochondrial DNA content. The phenotype was recapitulated by RYR1 silencing in mouse cellular myotube models. Altogether, these data indicate that remodelling of skeletal muscle Ca2+ signalling following loss of functional RyR1 mediates bioenergetic adaptation.

| S-EPMC6005141 | biostudies-literature

Inositol 1,4,5-Trisphosphate Receptors in Human Disease: A Comprehensive Update.

Project description:Inositol 1,4,5-trisphosphate receptors (ITPRs) are intracellular calcium release channels located on the endoplasmic reticulum of virtually every cell. Herein, we are reporting an updated systematic summary of the current knowledge on the functional role of ITPRs in human disorders. Specifically, we are describing the involvement of its loss-of-function and gain-of-function mutations in the pathogenesis of neurological, immunological, cardiovascular, and neoplastic human disease. Recent results from genome-wide association studies are also discussed.

| S-EPMC7231134 | biostudies-literature

Calcium modulates the generation of inositol 1,3,4-trisphosphate in human platelets by the activation of inositol 1,4,5-trisphosphate 3-kinase.

Project description:We observed that more total inositol trisphosphate (InsP3) was formed when human platelets were stimulated with agonists (15-hydroxy-9,11-azo-prosta-5,13-dienoic acid or thrombin) in the presence of extracellular Ca2+ than in its absence. Analysis of the InsP3 by h.p.l.c. indicated that the increased InsP3 formed in the presence of extracellular Ca2+ was primarily the 1,3,4-trisphosphate [Ins(1,3,4)P3]. In addition, more inositol 1,3,4,5-tetrakisphosphate (InsP4) was formed in the presence of extracellular Ca2+. Experiments conducted with electrically permeabilized platelets demonstrated that conversion of [3H]Ins(1,4,5)P3 to [3H]InsP4 in platelets was Ca2+-dependent, with half-maximal conversion observed at approx. 2.5 microM-Ca2+. By contrast, dephosphorylation of [3H]InsP4 to [3H]Ins(1,3,4)P3 was not activated by Ca2+. A partially purified preparation of Ins(1,4,5)P3 3-kinase from human platelets was found to be insensitive to Ca2+, but addition of calmodulin restored Ca2+-sensitivity to the kinase, increasing its activity about 5-fold. These results show that in human platelets the metabolism of Ins(1,4,5)P3 is regulated by Ca2+-calmodulin, and suggest that the metabolites of Ins(1,4,5)P3 may also have important second-messenger functions in platelets, and are consistent with the hypothesis that the activation of phospholipase C is not dependent on extracellular Ca2+.

| S-EPMC1149372 | biostudies-other

Inositol Trisphosphate Receptor Mediated Ca2+ Signalling Stimulates Mitochondrial Function and Gene Expression in Core Myopathy Patients [Mouse arrays]

2020-09-15 | GSE103853 | GEO