Inositol 1,4,5-trisphosphate production

Okubo Y., Kakizawa S., Hirose K., and lino M. (2004). Cross talk between metabotropic and ionotropic glutamate receptor- mediated signaling in parallel fiber-induced inositol 1,4,5-trisphosphate production in cerebellar Purkinje cells. J. Neurosci. 24 9513-9520. 

GU-7, a 3-arylcoumarin derivative, has been isolated fi om Glycyrrhizae radix, which is a crude herbal medicine. GU-7 caused inhibition of platelet aggregation, phosphorylation of 40K and 20K dalton proteins, inositol 1,4,5-trisphosphate production, intraplatelet calcium increase and phosphodiesterase activity in vitro. The data indicate that GU-7 inhibits platelet aggregation by increasing intraplatelet cAMP concentration. Antiplatelet action may also explain the mechanism by which traditional medicines are effective in diabetic neuropathy [236]. Osthole causes hypotension in vivo, and inhibits platelet aggregation and smooth muscle contraction in vitro. It may interfere with calcium influx and cyclic nucleotide phosphodiesterases [12]. Cloricromene, a synthetic coumarin derivative, also possesses antithrombotic-antiplatelet activity [237]. Some of these properties of cloricromene have been attributed to the inhibition of arachidonate release from membrane phospholipids [12]. 

I Kojima, H Shibata, E Ogata. (1986). Pertussis toxin blocks angiotensin II-induced calcium influx but not inositol trisphosphate production in adrenal glomerulosa cell. FEBS Lett 204 347-351. 

Inositol trisphosphate Receptor/G-protein cascades. As discussed above, IP3 is one of the products of the hydrolysis of PIP2. To say that it acts as a second messenger means that a rise in its concentration occurs as a result of some meaningful event and that the rise causes some other significant event. In terms of information flow, the signal immediately preceding the rise in IP3 is a rise in the concentration of active PLC. This rise is due to the binding of a subset of G-proteins... 

The phosphorylated phospholipid, phosphatidylinositol bisphosphate, is present in cell membranes. On hydrolysis by a phospholipase, it produces two products, inositol trisphosphate and diacylglycerol (Figure 11.25), as follows ... 

Further support for the hypothesis that Ca2+ plays a central role in regulating phytoalexin accumulation is provided by experiments in which the turnover of phosphatidylinositol was measured in the plasma membrane of elicitor-treated carrot cells [17]. The carrot cells were first labelled with [3H]myo-inositol and, after the addition of elicitors, acid extracts of the cells were analyzed chromatographically for the production of inositol trisphosphate (IP3). In cells treated with elicitor, the release of radioactive IP3 increased with time and attained a maximum at 3 - 5 min after treatment. Phospholipase activity responsible for the degradation of phosphorylated phosphatidylinositol increased correspondingly. Several reports have shown that IP3 induces rapid release of Ca2+ from intracellular stores in animal cells [18, 19]. Studies on plant cells have also demonstrated that exogenous IP3 releases Ca2+ from microsomal preparations at micromolar concentrations, although only limited... 

After activation of the TCR, there is induction of Src family tyrosine kinase (p56lek), which phosphorylates phospholipase Oyl. This is followed by the hydrolysis of phosphatidylinositol 4,5-bisphosphate, resulting in the production of diacyl-glycerol (DAG) and inositol trisphosphate (IP3). Protein kinase C is activated by DAG, which phosphorylates Ras. Ras is a GTPase and its phosphorylation induces Raf and initiation of MAP kinase signaling pathway. IP3 is involved in calcium-dependent activation of IL-2 gene expression via nuclear factor of activated T cells (NFAT). 

Fig. 2 Presynaptic mGluRs on human and rat neocortical cholinergic (ACh) nerve endings and effect of the HIV-1 protein Tat. In human neocortex, Tat activates mGluRl leading to inositol trisphosphate (IP3) production, IP3 receptor (IP3R) activation, mobilization of Ca2+ from the endoplasmic reticulum (ER), and vesicular ACh release. In rat neocortex ACh terminals Tat binds to an unidentified receptor whose activation also leads to ACh release. This release again is dependent on intraterminal Ca2+, but this is mobilized by ryanodine receptor (RYR) activation via the endogenous agonist cyclic adenosine diphosphoribose (cADPR).

Drbak, B.K., and Watkins, P.A., 2000, Inositol(l,4,5)trisphosphate production in plant cells an early response to salinity and hyperosmotic stress. FEBS Lett. 481 240-244. 

There are two major types of vasopressin receptors, VI and V2. The VI receptor occurs in vascular smooth muscle and is coupled via to activation of the phosphoinositide cascade-signaling system and generation of the second messenger inositol trisphosphate (IP3) and diacylglycerol. V2 receptors are found in kidney and are coupled via to activation of adenylate cyclase and production of the second messenger cyclic AMP. 

Little is known of the intracellular events involved in the augmentation of cyclic AMP accumulation elicited by H, -receptors in mammalian brain slices. However, it seems certain that another second messenger is involved, since the effect is not observed in membrane preparations [81, 205]. Calcium appears to be important for the response, since removal of external calcium reduces H,-receptor-mediated cyclic AMP accumulation in guinea-pig cerebral cortical slices [206]. Inositol phospholipid breakdown or its products (inositol trisphosphate and diacylglycerol) may also be involved, since H,-receptor stimulation is accompanied by an accumulation of inositol phosphates in slices of guinea-pig cerebral cortex [60, 207, 208]. Inositol trisphosphate may then... 

Effects at al receptors. When hormones acting at al receptors interact with the receptors, they cause an activation of phospholipase C via transduction, utilizing the G protein (as seen in Fig. 16.1). The products of phospholipase C are inositol trisphosphate (IP3), which increases cytosolic Ca2+, and diacylglycerol (DAG), which activates protein... 

Fig. 1. Stimulus-induced turnover of phosphatidylinositol 4,5-bisphosphate (PIPo) and the role of turnover products in signal transduction. PI, phosphatidylinositol PIP, phosphatidylinositol 4-phosphate PIPo, phosphatidylinositol 4,5 bisphosphate IP, inositol trisphosphate IP, inositol tetrakisphosphate IPo inositol bisphosphate IP, inositol monophosphate ER, endoplasmic reticulum DG, diacylglycerol MG, monoglyceride AA, arachidonic acid PA, phosphatidic acid. [Adapted from 38]...

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