SEARCH · Search PubMed

Results for “Inositol Phosphates”

Search indexed PubMed citations on genomics, clinical trials, systematic reviews and public health. Explore titles, authors and supplied subject terms, then open the PubMed record.

SourceResearch connectionFrom yearThrough year

Quote a phrase for an exact phrase match. Source license links do not imply unrestricted reuse.

At least 559 records · Page 31Linked to original sources

PubMed1989

N-formyl-methionyl-leucyl-phenylalanine induced accumulation of inositol phosphates indicates the presence of oligopeptide chemoattractant receptors on circulating human lymphocytes.

Using [3H]-inositol-labeled human lymphocytes, formation of inositolphosphates was found as a specific response to the chemotactic formylpeptide, N-formyl-methionyl-leucyl-phenylalanine (fMLP), in a fashion similar to the effects of fMLP in human granulocytes. Inositol phosphate formation could be significantly augmented by lithium ions. The results suggest that fMLP-mediated hydrolysis of phosphoinositides is involved in its chemotactic effects on human lymphocytes.

Adult↗

PubMed1994

Nitrergic stimulation does not inhibit carbachol-induced inositol phosphate generation in the rat anococcygeus.

Carbachol (50 microM) produced a rapid, transient increase in inositol-1,4,5-trisphosphate (IP3) levels in the rat anococcygeus; the peak increase observed at 10 s (3-fold above controls) was greatly reduced in the presence of atropine (100 nM), but was unaffected by nitrergic stimulation (10 Hz), sodium nitroprusside (10 microM) or 8-Br-cyclic GMP (200 microM). Following loading of muscles with [3H]myo-inositol, subsequent exposure to carbachol for 30 min resulted in a 6-fold increase in the accumulation of [3H]inositol-1-monophosphate; again, this action of carbachol was greatly attenuated by atropine, but unaffected by nitrergic stimulation, sodium nitroprusside or 8-Br-cyclic GMP. It is concluded that inhibition of agonist-induced generation of inositol phosphates cannot explain the ability of nitrergic activation to relax (by 54-62%) carbachol-induced tone in this tissue.

Anal Canal↗

PubMed2002

Effect of traditional, microwave and industrial cooking on inositol phosphate content in beans, chickpeas and lentils.

An high-performance liquid chromatography method for determining inositol phosphate fractions was adapted to legumes. The validity of the method was assessed by estimating the following analytical parameters: linearity (linear response between 125 and 5000 microg inositol hexaphosphate (IP(6))/ml); instrumental precision and method precision (relative standard deviation, %) were 1.9% (IP(6)) for instrumental, and 2.5% (IP(6)) and 8.2% (IP(5)) for method precision. An accuracy was estimated by percentage recovery (72 +/- 3%). The application of this method to raw, conventional, microwave-cooked and ready-to-eat beans, chickpeas and lentils gave IP(6) contents ranging from 0.63 g/100 g dry matter in ready-to-eat lentils to 1.87 g/100 g dry matter in raw beans. The IP(6) content was reduced by all the cooking procedures, while the relative percentage of inositol pentaphosphate increased in all the legumes studied, and reached the maximum of 31% (expressed in relation to dry matter) in ready-to-eat beans.

Chromatography, High Pressure Liquid↗

PubMed1990

Muscarinic cholinergic stimulation of inositol phosphate production in cultured embryonic chick atrial cells. Evidence for a role of two guanine-nucleotide-binding proteins.

These studies demonstrate a novel mechanism for the coupling of the muscarinic receptor to phospholipase C activity in embryonic chick atrial cells. In monolayer cultures of atrial cells from hearts of embryonic chicks at 14 days in ovo, carbamylcholine stimulated the sequential appearance of InsP3, InsP2 and InsP1 with an EC50 (concn. causing 50% of maximal stimulation) of 30 microM. In the presence of 15 mM-Li, a 5 min exposure to carbamylcholine (0.1 mM) increased InsP3 levels to a maximum of 47 +/- 12% over basal, InsP2 to 108 +/- 13% over basal and InsP1 to 42 +/- 5% over basal. This effect was blocked by 5 microM-atropine. Incubation of these cells with pertussis toxin (15 h; 0.5 ng/ml) inhibited carbamylcholine-stimulated InsP3, InsP2 and InsP1 formation by 42 +/- 7%, 30 +/- 3% and 48 +/- 7% respectively. The IC50 (concn. causing 50% inhibition) for pertussis toxin inhibition of all three inositol phosphates was 0.01 ng/ml, with a half-time of 6 h at 0.5 ng/ml. This partial sensitivity to pertussis toxin was not due to incomplete ADP-ribosylation of the guanine-nucleotide-binding protein (G-protein), since autoradiography of polyacrylamide gels of cell homogenates incubated with [32P]NAD+ in the presence of pertussis toxin demonstrated that incubation of cells with 0.5 ng of pertussis toxin/ml for 15 h resulted in complete ADP-ribosylation of pertussis toxin substrates by endogenous NAD+. In cells permeabilized with saponin (10 micrograms/ml), 0.1 mM-GTP[S] (guanosine 5'-[gamma-thio]triphosphate) stimulated InsP1 by 102 +/- 15% (mean +/- S.E.M., n = 4), InsP2 by 421 +/- 67% and InsP3 by 124 +/- 33% above basal. Incubation of cells for 15 h with 0.5 ng of pertussis toxin/ml decreased GTP[S]-stimulated InsP1 production in saponin-treated cells by 30 +/- 10% (n = 3), InsP2 production by 45 +/- 7% (n = 4) and InsP3 production by 49 +/- 6% (n = 4). These data demonstrate that in embryonic chick atrial cells at least two independent G-proteins, a pertussis toxin-sensitive G-protein and a pertussis toxin-insensitive G-protein, play a role in coupling muscarinic agonist binding to phospholipase C activation and to inositol phosphate production.

Adenosine Diphosphate Ribose↗

PubMed1987

Histamine stimulates inositol phosphate accumulation via the H1-receptor in cultured human endothelial cells.

The effects of histamine on [3H]inositol phosphate ([3H]IP) accumulation was examined in the presence of lithium in [3H]inositol-prelabelled human umbilical vein endothelial cells. Histamine stimulated total [3H]IP formation in a dose-dependent manner with a half-maximal value (EC50) of around 1-2 X 10(-6) M. Mepyramine, but not cimetidine, completely abolished the histamine response indicating that activation of phosphoinositide hydrolysis is mediated via H1-receptors. These data are the first to suggest that activation of inositol lipid hydrolysis is the underlying transmembrane signalling mechanism histamine H1-receptors employ in mediating various endothelial cell functions.

Cells, Cultured↗

PubMed1994

Time course of formation of inositol phosphates during enzymatic hydrolysis of phytic acid (myo-inositol hexaphosphoric acid) by phytase determined by capillary isotachophoresis.

Capillary isotachophoresis with conductivity detection was applied to the investigation of the hydrolytic decomposition of phytic acid (myo-inositol hexaphosphoric acid) by phytase, and for the formation of the reaction products as a function of time. The quantitation of all analytes (besides phytic acid the mono- to penta-phosphorylated inositols and orthophosphate) can be carried out using two different buffer systems.

6-Phytase↗

PubMed1991

Effects of transformation with the v-src oncogene on inositol phosphate metabolism in rat-1 fibroblasts. D-myo-inositol 1,4,5,6-tetrakisphosphate is increased in v-src-transformed rat-1 fibroblasts and can be synthesized from D-myo-inositol 1,3,4-trisphosphate in cytosolic extracts.

Rat-1 fibroblasts transformed with the v-src oncogene show a 6-fold increase in the apparent amount of an inositol polyphosphate which has a high performance liquid chromatography (HPLC) elution characteristic of the D/L-myo-inositol 1,4,5,6-tetrakisphosphate enantiomeric pair (Johnson, R.M., Wasilenko, W.J., Mattingly, R.R., Weber, M.J., and Garrison, J.C. (1989) Science 246, 121-124). By chemical and enzymatic analysis, the structure of this compound produced in both normal and v-src-transformed rat-1 fibroblasts has been determined to be principally D-myoinositol 1,4,5,6-tetrakisphosphate (D-Ins(1,4,5,6)P4). Chronic stimulation with endothelin-1 in the presence of Li+ significantly increased the amount of D/L-Ins(1,4,5,6)P4 only in the v-src-transformed rat-1 cells, suggesting that production of this compound may be remotely coupled to long term agonist-induced phosphatidylinositol turnover. Further evidence for such a link is provided by the progressive loss of D-Ins(1,4,5,6)P4 from the normal cells deprived of serum stimulation. To define a possible synthetic pathway for D-Ins(1,4,5,6)P4, cytosolic extracts of normal and v-src-transformed cells were incubated with [3H]inositol polyphosphates, and the reaction products were identified by HPLC elution and chemical analysis. Although inositol 1,3,4-trisphosphate 6-kinase activity was prominent in extracts of both normal and transformed cells, only the cytosol from v-src-transformed cells ultimately formed measurable amounts of D-Ins(1,4,5,6)P4 from [3H]inositol 1,3,4-trisphosphate. Approximately 6% of 0.1 microM inositol 1,3,4-trisphosphate was converted to D-Ins(1,4,5,6)P4 during a 2-h incubation at 37 degrees C. Inositol pentakisphosphate was identified as a likely intermediate in this conversion, and extracts of both normal and transformed cells converted [3H]inositol 1,3,4,5,6-pentakisphosphate to D-Ins(1,4,5,6)P4. The synthetic pathway described is consistent with the long term regulation of D/L-Ins(1,4,5,6)P4 levels in rat-1 fibroblasts seen in response to src transformation, serum withdrawal, and chronic endothelin treatment, and identifies several new potential interactions between the pathways of inositol polyphosphate metabolism and those of src transformation.

Animals↗

PubMed1990

Paradoxical digestion of myo-inositol phosphates by alkaline phosphatase at low pH.

The ability of bovine intestinal alkaline phosphatase (0.1-10 units/ml) to cleave myo-inositol bound phosphate moieties was examined. Paradoxically the digestion was optimal for a number of isomers at pH 5-7. It is possible that digestion at higher pH (9-10) does not proceed at maximal rates due to a conformation of the myo-inositol phosphate molecule which stabilizes the molecule against enzymatic attack. Alkaline phosphatase activity did not require the addition of added divalent cations. Moreover, several divalent cations, particularly zinc, were found to have a marked inhibitory effect. Further studies into this phenomenon suggested that some divalent cations can form insoluble complexes with myo-inositol phosphates, particularly those possessing a number of phosphate moieties, preventing the action of degradative enzymes. On the basis of these experiments we conclude that phosphate moieties can be removed from myo-inositol using relatively low concentrations of alkaline phosphatase as long as optimal incubation conditions are selected. This includes the use of a slightly acidic incubation media without the addition of divalent cations, particularly zinc.

Alkaline Phosphatase↗

PubMed1989

Scrape-loaded p21ras down-regulates agonist-stimulated inositol phosphate production by a mechanism involving protein kinase C.

The effect of scrape-loaded [Val-12]p21ras on agonist-stimulated phosphatidylinositol 4,5-bisphosphate (PIP2) turnover in Swiss-3T3 cells was studied. Previously [Morris, Price, Lloyd, Marshall & Hall (1989) Oncogene 4, 27-31] we demonstrated that [Val-12]p21ras activates protein kinase C within 10 min of scrape loading. Here, we show that [Val-12]p21ras inhibits bombesin and platelet-derived growth factor-stimulated PIP2 breakdown 1.5-4 h after scrape loading. This effect persisted for at least 18 h and could be mimicked in control cells by activation of protein kinase C with 12-O-tetradecanoyl 13-acetate (TPA) 15 min prior to ligand stimulation. When protein kinase C was down-regulated by chronic TPA treatment, [Val-12]p21ras was no longer able to inhibit agonist-stimulated inositol phosphate production. These results indicate that changes in inositol phosphate levels caused by ras protein are probably due to activation of protein kinase C and not to an interaction of ras with phospholipase C.

Animals↗

PubMed1991

The effect of glycosyl inositol-phosphate on cAMP production in isolated rat fat-cells is transduced by a pertussis toxin sensitive G-protein.

In fat-cells, insulin increases synergistically the inhibitory effects of adenosine and prostaglandin E2 on adenylyl cyclase activity. When the endogenous production of these feedback inhibitors is suppressed, insulin is no more active in conditions where glycosyl inositol-phosphate which is a putative mediator of its action, is always efficient. Moreover, glycosyl inositol-phosphate signal is transduced by a G protein sensitive to IAP intoxication.

Adenosine↗

PubMed1992

P2 purinoceptors stimulate inositol phosphate release in the organ of Corti.

We examined the effects of purinoceptor agonists on inositol phosphate (IP) release in the guinea-pig organ of Corti. The P2y receptor agonist ATP-gamma-S (200 microM) increased IPs 4-fold; identical concentrations of alpha, beta-methylene ATP, a P2x agonist, and adenosine, a P1 agonist, did not significantly affect IP release. In calcium-free incubations, simulated IP release decreased by 35% indicating partial dependence of ATP-mediated phosphoinositide hydrolysis on calcium influx. ATP-stimulated IP release was not enhanced by the cholinergic agonist carbachol known to increase IPs via muscarinic receptors in the organ of Corti. This is consistent with the notion that ATP and carbachol have a common target, most likely outer hair cells. P2 purinoceptors coupled to the phosphoinositide cascade suggest ATP as an afferent neuromodulator or efferent neurotransmitter in the cochlea.

Animals↗

PubMed1990

Potentiation by gamma-aminobutyric acid of alpha 1-agonist-induced accumulation of inositol phosphates in slices of rat cerebral cortex.

Noradrenaline-induced accumulation of 3H-labeled inositol mono-, bis-, and trisphosphate (IP1, IP2, and IP3, respectively) in lithium-treated slices of rat cerebral cortex preincubated with [3H]inositol was potentiated by gamma-aminobutyric acid (GABA). However, the effect on [3H]IP2 accumulation was much greater than that on [3H]IP1 or [3H]IP3 accumulation. The principal effect of GABA on noradrenaline concentration-response curves for both [3H]IP1 and [3H]IP2 was to cause an increase in the maximal response attainable. However, whereas the EC50 for GABA potentiation of [3H]IP1 formation was 0.5 mM, the curve for the potentiation of [3H]IP2 formation showed a marked upturn at GABA concentrations of greater than 1 mM. Prazosin (1 microM) blocked the noradrenaline-induced formation of all three inositol phosphates (IPs), in both the presence and the absence of 2 mM GABA. 3H-IP formation induced by phenylephrine and methoxamine was also potentiated by GABA, and again the greatest effect was on [3H]IP2 accumulation. The ratio of [3H]IP2/[3H]IP1 formed in response to 100 microM noradrenaline was increased by 2 mM GABA at all times from 10 to 60 min, whereas the ratio of [3H]IP3/[3H]IP1 was little altered. The effect of GABA was not mimicked by the GABAA agonists isoguvacine and 3-aminopropanesulphonic acid and was not blocked by bicuculline methiodide. (-)-Baclofen, a GABAB agonist, did produce some stimulation of the response to noradrenaline, but to a much lesser extent than GABA. Of the agents tested, nipecotic acid came nearest to reproducing the effect of GABA, in that the major effect was on [3H]IP2 accumulation. The effects of 2 mM GABA and 2 mM nipecotic acid were not additive. GABA potentiation of noradrenaline-induced 3H-IP formation was still apparent in the absence of Li+, but the increase of [3H]IP2 content was less than that of [3H]IP1 content.

Adrenergic alpha-Agonists↗

PubMed1992

Histamine activates phosphorylase and inositol phosphate production in guinea pig hepatocytes.

In guinea pig hepatocytes, histamine increased phosphorylase activity and inositol phosphate production. Similar effects were obtained with 2-(2-aminoethyl)-thiazole, a histamine H1 receptor agonist, but not with dimaprit or impromidine, H2 receptor agonists. These effects of histamine were dose-dependently inhibited by the H1 antihistamines, (+)-chlorpheniramine and mepyramine (pyrilamine) but not by cimetidine or ranitidine, H2 antagonists. (+)-Chlorpheniramine and mepyramine had similar potencies (apparent Ki values approximately 3 nM) when incubated with the cells for 1 min (phosphorylase a assays) but the former was 15-20-fold more potent than the latter at longer incubation times (apparent Ki values approximately 3-4 nM and 45-90 nM, respectively) indicating that mepyramine is actively metabolized by guinea pig hepatocytes. Histamine increased cytosol calcium approximately 2-fold, an effect also mediated through H1 receptors. The actions of histamine were not affected by in vivo ADP-ribosylation by pertussis toxin. Our data clearly indicate that histamine modulates the metabolism of guinea pig hepatocytes via activation of H1 receptors. These receptors are coupled to the phosphoinositide turnover-calcium mobilization signalling pathway through a pertussis toxin-insensitive process.

Animals↗

PubMed1990

Different pathways of [3H]inositol phosphate formation mediated by alpha 1a- and alpha 1b-adrenergic receptors.

The types of inositol phosphates (InsPs) formed in response to activation of alpha 1-adrenergic receptor subtypes were determined in collagenase-dispersed renal cells and hepatocytes by high pressure liquid chromatography separation. In hepatocytes, which contain only the alpha 1b subtype, norepinephrine stimulated rapid (10-s) formation of [3H]Ins(1,4,5)P3 and [3H]Ins(1,3,4)P3 and slower (5-min) formation of Ins(1,4)P2 and Ins(1)P. Selective inactivation of alpha 1b receptors by chloroethylclonidine almost completely blocked the effects of norepinephrine in hepatocytes. In renal cells, which contain both alpha 1a and alpha 1b receptors in a 60:40 ratio, norepinephrine did not significantly increase the size of any peaks until 5 min after agonist activation. At this time, only a peak eluting with Ins(1)P and one eluting shortly after Ins(1,4)P2 were significantly elevated. Incubation with norepinephrine for 2 h caused small but significant increases in peaks co-eluting with Ins(1)P and Ins(1,4,5)P3 in renal cells; however, only the increase in Ins(1)P was inhibited by chloroethylclonidine pretreatment. Extraction under neutral conditions suggested that cyclic InsPs may be the primary compounds formed in response to norepinephrine in renal cells. Removal of extracellular Ca2+ caused a 60% reduction in the InsP response to norepinephrine in renal cells but had no effect in hepatocytes. These results suggest that activation of alpha 1a and alpha 1b receptor subtypes results in formation of different InsPs and that the response to alpha 1a activation may require influx of extracellular Ca2+.

Animals↗

PubMed1992

Gonadotropin-releasing hormone-stimulated intracellular Ca2+ fluctuations and luteinizing hormone release can be uncoupled from inositol phosphate production.

In order to study the dependence of GnRH-stimulated LH release on inositol phosphate (IP) turnover, this study used an inhibitor of phospholipase C activity, 1-[6-[[17 beta-3- methoxyestra-1,3,5(10)-triene-17-yl]amino]hexyl]-1H-pyrrole-dione (U-73122) and an inactive analog 1-[6[[17 beta-3-methoxyestra-1,3,5(10)- triene-17-yl]amino]hexyl]2,5-pyrrolidine-dione (U-73343). U-73122 (10 microM) decreased GnRH-provoked (1 microM, 45 min) IP accumulation from 873 +/- 61 dpm to 365 +/- 50 dpm (basal accumulation also was decreased from 420 +/- 18 dpm to 207 +/- 16 dpm) while LH release was not inhibited (30.2 +/- 1.4% of cellular LH in control compared to 30.3 +/- 1.1% in U-73122 pretreated cells). GnRH provoked increased IP3 accumulation (123% of basal) after 15 sec of stimulation, IP2 accumulation (131% of basal) after 30 sec, and IP1 (121% of basal) after 1 min. Pretreatment with U-73122 blocked accumulation of IPs at these early timepoints. Sodium fluoride (NaF)-stimulated IP accumulation was also inhibited by U-73122 (from 1539 +/- 132 dpm to 414 +/- 21 dpm) while LH release increased from 22.9 +/- 1.4% total cellular LH to 28.0 +/- 2.2%. In contrast, GnRH- and NaF-stimulated IP accumulation were not significantly decreased in U-73343 pretreated cells (GnRH: 817 +/- 43 dpm compared to 873 +/- 61 dpm in control; NaF: 1133 +/- 74 dpm compared to 1539 +/- 132 dpm in control cells). Results of a perifusion study showed that U-73122 did not block the initial phase of GnRH-stimulated LH release or interfere with the development of desensitization to the releasing hormone. In addition, GnRH-stimulated intracellular Ca2+ fluctuations were similar in magnitude and duration in U-73122-pretreated compared to U-73343-pretreated cells. These results demonstrate that GnRH- as well as NaF-stimulated LH release can be uncoupled from IP production calling to question the role of IP3 as a second messenger for GnRH-stimulated LH release.

Animals↗

PubMed2000

Diphospho-myo-inositol phosphates during the life cycle of Dictyostelium and Polysphondylium.

The intracellular amounts of diphospho-myo-inositol phosphates and InsP6 were determined in Dictyostelium discoideum AX2 throughout the life cycle, including exponential growth, starvation, differentiation, sporulation and spore germination. Similar experiments were performed with the closely related species Polysphondylium pallidum under conditions resulting in microcyst formation. A distinct accumulation of these compounds is observed during the early starvation phase of the cell population before the onset of the actual differentiation program. When exponentially growing D. discoideum cells were shifted to starvation conditions, a 25-fold accumulation of 5,6-bis-PP-InsP4 within 3 h was observed. In P. pallidum, the 5,6-bis-PP-InsP4 pool rises around 20-fold within 8 h during the formation of microcysts from vegetative cells. Finally, the diphosphoinositol phosphates are deposited in spores or microcysts and are degraded when spores or microcysts germinate at low cell density.

Animals↗

PubMed1993

Receptor cross-talk can optimize assays for autoantibodies to the thyrotropin receptor: effect of phenylisopropyladenosine on adenosine 3',5'-monophosphate and inositol phosphate levels in rat FRTL-5 thyroid cells.

Immunoglobulins (IgG) from patients with Graves' disease increase inositol phosphate (IP) as well as cAMP production in rat thyroid FRTL-5 cells; IgGs from normal control subjects do not. Graves' IgG-and TSH-induced IP formation is inhibited by blocking TSH receptor (TSHR) antibodies from hypothyroid patients with primary myxedema, as is the cAMP response; this suggests that the Graves' IgG are acting through the TSHR to induce both the cAMP and phosphatidyl-inositol 4,5-biphosphate signal cascades in FRTL-5 thyroid cells as in cells with recombinant TSHR. Optimal conditions for measuring the Graves' IgG-induced IP increase include a NaCl-free Hanks' Balanced Salt Solution (HBSS) buffer system and a P1 purinergic receptor agonist; the action of each is additive. Optimization by NaCl-free HBSS is similar to that observed in cAMP assays and is specific for TSH or Graves' IgG; thus, NaCl-free HBSS did not affect ATP-induced, and actually inhibited norepinephrine-induced, IP production in FRTL-5 cells. The P1 purinergic receptor agonist acts via receptor cross-talk, which also allows further optimization of cAMP assays. Thus, adenosine deaminase improves Graves' IgG-induced cAMP production by removing adenosine from the medium. Although NaCl-free HBSS improved TSH- or Graves' IgG-induced IP and cAMP production in cells with recombinant TSHR; the modulatory action of phenylisopropyladenosine was lost.

Animals↗

PubMed1988

Inhibition of the amplified bombesin-stimulated inositol phosphate response in N-ras transformed cells by high density culturing.

The bombesin-stimulated inositol phosphate response is only increased in cells transformed by the overexpression of N-ras when they are cultured under sub-confluent conditions. The inhibition of the amplified bombesin stimulation can be partially reversed by either, incubation of the cells for 5 h with 1 mM suramin, or by a 30 min preincubation of cells in excess buffer. The inhibitory effects are probably caused by the effects of autocrines and may explain some of the different published observations concerning the effects of ras gene products upon inositol phospholipid metabolism.

Bombesin↗