Disease relevance of inositol 1,4,5-trisphosphate

• A tenfold increase in phospholipase C activity specific for phosphatidylinositol 4,5-bisphosphate (PIP2) was immunopurified from extracts of A-431 epidermoid carcinoma cells stimulated with epidermal growth factor [1].
• HIV-1 Nef interacts with inositol trisphosphate receptor to activate calcium signaling in T cells [2].
• Effect of thrombin on calcium homeostasis in chick embryonic heart cells. Receptor-operated calcium entry with inositol trisphosphate and a pertussis toxin-sensitive G protein as second messengers [3].
• Thus, hypoxia, which increases alpha 1-adrenergic receptor density, also leads to an enhanced production of inositol trisphosphate and could account for the enhanced alpha 1-adrenergic responsivity in the ischemic heart in vivo, which is known to facilitate arrhythmogenesis [4].
• Diminished agonist-stimulated inositol trisphosphate generation blocks stimulus-secretion coupling in mouse pancreatic acini during diet-induced experimental pancreatitis [5].

Psychiatry related information on inositol 1,4,5-trisphosphate

• It was found that there were no significant difference in [3H]Ins(1,4,5)P3 binding with respect to the number of sites measured at different protein concentrations or to the sensitivity of the binding to inhibition by nonradioactive Ins(1,4,5)P3 between Alzheimer disease platelets and controls [6].
• CONCLUSION: This longitudinal study suggests that therapeutic doses of lithium significantly decrease platelet membrane PIP2 levels in vivo in bipolar disorder subjects, which may be related to lithium's mechanism of action in bipolar disorder [7].
• Electroconvulsive shock stimulates polyphosphoinositide degradation and inositol trisphosphate accumulation in rat cerebrum: lithium pretreatment does not potentiate these changes [8].
• Finally, a possible significance of microvillous olfactory epithelial cells and inositol trisphosphate in olfaction will be discussed [9].

High impact information on inositol 1,4,5-trisphosphate

• Inositol trisphosphate and diacylglycerol: two interacting second messengers [10].
• Gap junction channels are responsible for direct intercellular transfer of ions and small molecules including propagation of inositol trisphosphate-dependent calcium waves [11].
• We find that TIRAP contains a phosphatidylinositol 4,5-bisphosphate (PIP2) binding domain, which mediates TIRAP recruitment to the plasma membrane [12].
• PIP2 and PIP3: complex roles at the cell surface [13].
• Here we use optical tweezers tether force measurements and show that plasma membrane phosphatidylinositol 4,5-bisphosphate (PIP2) acts as a second messenger that regulates the adhesion energy between the cytoskeleton and the plasma membrane [14].

Chemical compound and disease context of inositol 1,4,5-trisphosphate

• Hypoxia produced a marked leftward shift in the dose-response curve for the production of inositol trisphosphate in response to norepinephrine stimulation (EC50 = 1.2 x 10(-8) M) [4].
• Using this method, we detected elevated concentrations of PIP2 in human fibroblasts from patients with Lowe syndrome, a genetic disorder that affects phosphoinositide metabolism [15].
• When myocardial phosphoinositides were prelabeled with [3H]inositol, reperfusion after 30 minutes of normothermic global ischemia resulted in significant accumulations of radiolabeled inositol phosphate, inositol bisphosphate, and inositol trisphosphate [16].
• Though believed to lack receptors for pertussis toxin, intact platelets, when incubated with the toxin (5-20 micrograms/ml), undergo aggregation and accumulate inositol trisphosphate and phosphatidic acid [17].
• Incubation of intact PMNs, with the Bordetella pertussis toxin (islet-activating protein) eliminated the ability of fMet-Leu-Phe plus GTP to promote PIP2 breakdown in the isolated plasma membranes, but did not inhibit PIP2 degradation in the presence of 1 mM CaCl2 [18].

Biological context of inositol 1,4,5-trisphosphate

• Based on the in vitro effects of PI-TP, we surmise that it is involved in transporting PI from intracellular compartments for conversion to PI bisphosphate (PIP2) prior to hydrolysis by PLC-beta 2/PLC-beta 3, the endogenous PLC isoforms present in these cells [19].
• We have found that levels of the phosphatidylinositol metabolites inositol-trisphosphate and diacylglycerol significantly decrease within 2 hr of induction of Friend cell differentiation [20].
• Our study suggests that plasma membrane PIP2 controls dynamic membrane functions and cell shape by locally increasing and decreasing the adhesion between the actin-based cortical cytoskeleton and the plasma membrane [14].
• PIP2, which is regulated by activation stimuli, is sufficient in vitro to target the BAF complex to chromatin, but it has no effect on related chromatin remodeling complexes containing SNF2L or hISWI [21].
• Activation of at least ERM proteins can be accomplished by C-terminal phosphorylation in the presence of PIP2 [22].

Anatomical context of inositol 1,4,5-trisphosphate

• Thrombin stimulates 32Pi incorporation into phosphatidylinositol 4-phosphate (PIP), phosphatidylinositol 4,5-bis-phosphate (PIP2), and phosphatidylinositol (PI), and initiates DNA synthesis in hamster (NIL) fibroblasts at a half-maximal concentration of 125 ng/ml [23].
• An Ins(1,4,5)P3 binding protein, purified from brain membranes, has been shown to be phosphorylated by cyclic-AMP-dependent protein kinase and localized by immunohistochemical techniques to intracellular particles associated with the endoplasmic reticulum [24].
• Inositol 1,4,5-trisphosphate (Ins(1,4,5)P3) has recently been shown to mobilize Ca2+ from intracellular stores, referable to endoplasmic reticulum, in a variety of cell types (see ref. 8 for review), including smooth muscle cells of the porcine coronary artery and canine cardiac muscle cells [25].
• Bell-shaped calcium-response curves of Ins(1,4,5)P3- and calcium-gated channels from endoplasmic reticulum of cerebellum [26].
• Here we report that Ins(1,4,5)P3-induced channel activation in permeabilized hepatocytes is followed by a time-dependent inactivation, which is a direct consequence of ligand binding [27].

Associations of inositol 1,4,5-trisphosphate with other chemical compounds

• Melatonin receptor regulates several second messengers: cAMP, cGMP, diacylglycerol, inositol trisphosphate, arachidonic acid, and intracellular Ca2+ concentration ([Ca2+]i) [28].
• On the basis of certain structural requirements for Ca2+-releasing activity by inositol phosphates, it has been postulated that Ins(1,4,5)P3 acts by binding to a specific intracellular receptor, probably on a component of the endoplasmic reticulum [29].
• Inositol 1,4,5-trisphosphate (Ins(1,4,5)P3) serves as an intracellular second messenger for several neurotransmitters, hormones and growth factors by initiating calcium release from intracellular stores [30].
• We report here that the phosphoinositide messenger system oscillates during the early embryonic cell cycle in the sea urchin, leading to cyclic increases in inositol trisphosphate that trigger cell-cycle [Ca2+]i transients and mitosis by calcium release from intracellular stores [31].
• Two of the earliest events seen after stimulation are the hydrolysis of phosphatidylinositol bisphosphate to inositol trisphosphate (Ins P3) and 1,2-diacylglycerol (DAG), and an increase in the concentration of intracellular Ca2+ ([Ca2+]i) [32].

Gene context of inositol 1,4,5-trisphosphate

• N-WASP is tightly regulated by multiple signals: Only costimulation by Cdc42 and phosphatidylinositol (4,5)-bisphosphate (PIP2) yields potent polymerization [33].
• We report here that this Rac1-dependent pathway involves recruitment of phosphoinositol-4-phosphate-5-kinase (PIP5K) to form phosphoinositol-4,5-bisphosphate (PIP2) at the phagocytic cup [34].
• The results suggest that Ca2+ influx prevents PIP2 depletion by inhibiting PLC activity and facilitating PIP2 recycling [35].
• Calcium influx via TRP channels is required to maintain PIP2 levels in Drosophila photoreceptors [35].
• Two independent mutations in the PIP2 recycling pathway (rdgB and cds) prevented recovery from inactivation [35].

Analytical, diagnostic and therapeutic context of inositol 1,4,5-trisphosphate

• A cerebellar Ins(1,4,5)P3 receptor has been characterized biochemically and shown by immunocytochemistry to be present in intracellular membranes in Purkinje cells [30].
• Mitogenesis in response to PDGF and bombesin abolished by microinjection of antibody to PIP2 [36].
• Using genetically targeted PIP2-sensitive inward rectifier channels (Kir2.1) as biosensors, we provide evidence that trp decay reflects depletion of PIP2 [35].
• Partially purified DdLIMP bound specifically to PIP2 in sedimentation and gel filtration assays [37].
• Electrical stimulation of hippocampal neurons resulted in a decrease of the PH-GFP signal at the plasma membrane, most probably due to a PLC-mediated hydrolysis of PIP2 [38].

References