Inositol trisphosphate calcium mobilization

Kiang JG, Smallridge RC. 1994. Sodium cyanide increases cytosolic free calcium evidence for activation of the reversed mode of the Na+/Ca2+ exchanger and Ca2+ mobilization from inositol trisphosphate-insensitive pools. Toxicol Appl Pharmacol 127(2) 173-181. 

The effects of VIP are mediated by G protein-coupled receptors two subtypes, VPAC1 and VPAC2, have been cloned from human tissues. Both subtypes are widely distributed in the central nervous system and in the heart, blood vessels, and other tissues. VIP has a high affinity for both receptor subtypes. Binding of VIP to its receptors results in activation of adenylyl cyclase and formation of cAMP, which is responsible for the vasodilation and many other effects of the peptide. Other actions may be mediated by inositol trisphosphate synthesis and calcium mobilization. 

The actions of substance P and neurokinins A and are mediated by three G protein-coupled tachykinin receptors designated NK i, NK 2, and NK 3. Substance P is the preferred ligand for the NK receptor, the predominant tachykinin receptor in the human brain. However, neurokinins A and also possess considerable affinity for this receptor. In humans, most of the central and peripheral effects of substance P are mediated by NKi receptors. All three receptor subtypes are coupled to inositol trisphosphate synthesis and calcium mobilization. 

Falsafi R, Tatakis DN, Hagel-Bradway S, Dziak R. 1991. Effects of inositol trisphosphate on calcium mobilization in bone cells. Calcif Tissue Int 49 333-9. 

Further studies have revealed that pumiliotoxin B interacts with voltage-dependent sodium channels to elicit an increased influx of sodium ions (101,102) and, in brain and heart preparations, a stimulation of phosphoino-sitide breakdown (101,103-106). The phosphoinositide breakdown can, via inositol trisphosphate, cause release of calcium from internal storage sites. The cardiotonic activity of pumiliotoxin B and various congeners and synthetic analogs correlates well with the stimulation of phosphoinositide breakdown (104,105). A number of studies on stimulation of sodium uptake by pumiliotoxin B and inhibition by local anesthetics and other agents have appeared (106-108). The effects of pumiliotoxin B on neuromuscular preparations have been reinterpreted as due primarily to effects on sodium channels, although additional direct effects on calcium mobilization remain possible (109). It has recently been proposed that pumiliotoxin B enhances the rate of activation of sodium channels (110). One characteristic effect of pumiliotoxin B is to elicit repetitive firing in neurons, apparently because of effects on sodium channel function (109-111). 

DeWald, D.B., Torabinejad, J., Jones, C.A., Shope, J.C., Cangelosi, A.R., Thompson, J.E., Prestwich, G.D., and Hama, H., 2001, Rapid accumulation of phosphatidylinositol 4,5-bisphosphate and inositol 1,4,5-trisphosphate correlates with calcium mobilization in salt-stressed Arabidopsis. Plant Physiol. 126 759-769. 

IQindu, N. and Huzoor-Akbar Inositol trisphosphate generation and mobilization of calcium is increased... 

Lee, H. C., and Aarhus, R. (1995). A derivative of NADP mobilizes calcium stores insensitive to inositol trisphosphate and cyclic ADP-ribose. J. Biol Chem. 270,2152-2157. 

It is now generally accepted that both of the products of phosphatidylinositol 4,5-bisphosphate hydrolysis can function as intracellular second messengers. 1,2-Diacylglycerol can affect a variety of intracellular processes by activation of protein kinase C [ 148, 229, 230]. Inositol 1,4,5-trisphosphate, on the other hand, has been shown to release calcium ions from non-mitochondrial stores in a number of peripheral tissues and may thus be the link between the receptor and the intracellular calcium store in many pharmacological responses [231-233]. Furthermore, it remains a possibility that inositol phospholipid hydrolysis may also have a r61e in calcium gating [221,234]. If inositol phospholipid metabolism is closely coupled to receptor-mediated calcium mobilization, then this response may be a more general consequence of H,-receptor stimulation than other H,-responses. 

Many oncogenes such as ras, src, sis, fms, and fes enhance cellular PI turnover. Phosphatidyl breakdown by phospholipase C generates two second messengers, diacyIglycerol and inositol trisphosphate. The formed directly activates protein kinase C, and the latter binds to the receptor on endoplasmic reticulum to mobilize calcium ions. Therefore, we screened culture filtrates of microorganisms for inhibitors of PI turnover and thus isolated psi-tectorigenin (Fig. 11, ref. 23). ... 

The anthranilamide, DP-012, stimulates a rise in [Ce ]i under conditions of Ca -free saline similar to that observed with standard saline, indicating that this chemistry mobilizes calcium from internal calcium stores rather than through external entry via voltage-gated Ca channels. Three possible targets are involved in release of internal calcium stores, inositol trisphosphate receptors (IP3RS), ryanodine receptors (RyRs), and sarco-endoplasmic reticulum ATPase (SERCA). These P. americana neurons possess fimctional ryanodine receptors. 

Kaplin Al, Snyder SH, Linden DJ. 1996. Reduced nicotinamide adenine dinucleotide-selective stimulation of inositol 1,4,5-trisphosphate receptors mediates hypoxic mobilization of calcium. The Journal of Neuroscience 16(6) 2002-2011. 

Neurotransmitters, photons and hormones stimulate receptors on the surface of the target cells causing mobilization of the calcium ion in intracellular stores, thereby triggering physiological responses to occur. The physiological process had been known but it was not clear how the outer information (first messengers), which cannot permeate the cell membrane, was transmitted to the calcium stores. In 1983, this question was resolved by showing experimentally that D-myo-inositol 1, 4, 5-trisphosphate... 

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