Inositol 1,4,5-trisphosphate calcium release

The signal transduction mechanisms triggered by binding of ET-1 to its vascular receptors include stimulation of phospholipase C, formation of inositol trisphosphate, and release of calcium from the endoplasmic reticulum, which results in vasoconstriction. Conversely, stimulation of PGI2 and nitric oxide synthesis results in decreased intracellular calcium concentration and vasodilation. 

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). 

McGrath J, Solter D 1984 Inability of mouse blastomere nuclei transferred to enucleated zygotes to support development invitro. Science 226 1317-1319 Miyazaki S 1988 Inositol 1,4,5-trisphosphate-induced calcium release and guanine nucleotidebinding protein-mediated periodic calcium rises in golden hamster eggs. J Cell Biol 106 345-353... 

Yang, J., McBride, S., Mak, D. O. etal. Identification of a family of calcium sensors as protein ligands of inositol trisphosphate receptor Ca(2+) release channels. Proc. Natl Acad. Sci. U.S.A. 99 7711-7716, 2002. 

Missiaen L, Taylor CW, Berridge MJ 1992 Luminal Ca2+ promoting spontaneous Ca2+ release from inositol trisphosphate-sensitive stores in rat hepatocytes. J Physiol 455 623-640 Nazer MA, van Breemen C 1998 Functional linkage of Na+-Ca2+ exchange and sarcoplasmic reticulum Ca2+ release mediates Ca2+ cycling in vascular smooth muscle. Cell Calcium 24 275-283... 

Bulbring E, T omita T 1969 Effect of calcium, barium and manganese on the action of adrenaline in the smooth muscle of the guinea-pig taenia coli. Proc R Soc Lond B Biol Sci 172 121-136 Marchant JS, Taylor CW 1998 Rapid activation and partial inactivation of inositol trisphosphate receptors by inositol trisphosphate. Biochemistry 37 11524-11533 Somlyo AV, Horiuti K, Trentham DR, Kitazawa T, Somlyo AP 1992 Kinetics of Ca2+ release and contraction induced by photolysis of caged D-myo-inositol 1,4,5-trisphosphate in smooth muscle the effects of heparin, procaine, and adenine nucleotides. J Biol Chem 267 22316-22322... 

Finch EA, Turner TJ, Goldin SM 1991 Calcium as a coagonist of inositol 1,4,5-trisphosphate-induced calcium release. Science 252 443-446... 

Figure 14-3. Signaling through protein kinase C (PKC). Activated phospholipase C cleaves the inositol phospholipid PIP2 to form both soluble (IP3) and membrane-associated (DAG) second messengers. DAG recruits PKC to the membrane, where binding of calcium ions to PKC fully activates it. To accomplish this, IP3 promotes a transient increase of intracellular concentration by binding to a receptor on the endoplasmic reticulum, which opens a channel allowing release of stored calcium ions. PIP2, phosphatidylinositol 4,5-bisphosphate DAG, diacylglycerol PLC, phospholipase C IP3, inositol trisphosphate.

Three subtypes of vasopressin G protein-coupled receptors have been identified. Via receptors mediate the vasoconstrictor action of vasopressin V , receptors potentiate the release of ACTH by pituitary corticotropes and V 2 receptors mediate the antidiuretic action. Via effects are mediated by activation of phospholipase C, formation of inositol trisphosphate, and increased intracellular calcium concentration. V2 effects are mediated by activation of adenylyl cyclase. 

The main molecular target of LSD and other hallucinogens is the 5-HT2A receptor. This receptor couples to G proteins of the Gq type and generates inositol trisphosphate (IP3), leading to a release of intracellular calcium. Although hallucinogens, and LSD in particular, have been proposed for several therapeutic indications, efficacy has never been demonstrated. 

The large amount of work in this area reported by Russian workers and covered in our previous review [1] has also been reviewed by the Russian workers [284], These glycolipids have recently acquired a vastly increased biological interest since the discovery that various agonists at the cell surface stimulate a phospholipase which releases D-wiyo-inositol 1,4,5-trisphosphate from the membrane-bound phosphatidyl-inositol-4,5-bisphosphate. The released inositol trisphosphate acts as a second messenger by mobilising intra-cellular calcium ions [285-290]. 

Derived from Hodgkin-Huxley s celebrated theory and inspired by the experimental observations, cellular calcium dynamics, either stimulated via inositol 1,4,5-trisphosphate (IP3) receptor in many non-muscle cells [69,139], or via the ryanodine receptor in muscle cells [108], is another extensively studied oscillatory system. Both receptors are themselves Ca2+ channels, and both can be activated by Ca2+, leading to calcium-induced calcium release from endoplasmic reticulum. 

In osteoblasts, keratinocytes, and colonocytes, andpossibly other cells, calcitriol acts via cell surface receptors linked to phospholipase C, resulting in release of diacylglycerol and inositol trisphosphate (Section 14.4.1), followed by opening of intracellular calcium channels and activation of protein kinase C and mitogen-activated protein (MAP) kinases. The effect of this is inhibition of cell proliferation and induction of differentiation. A variety of analogs of calcitriol that do not bind to the nuclear receptor do bind to, and activate, the cell surface receptor, including l,25-dihydroxy-7-dehydrocholesterol and 1,25-dihydroxylumisterol. The rapid nongenomic responses to vitamin D can be demonstrated in knockout mice that lack the vitamin D nuclear receptor (Farach-Carson and Ridall, 1998 Nemere and Farach-Carson, 1998). 

Both cADP-rihose and NAADP act to increase cytosolic calcium concentrations, releasing calcium from intracellular stores via a receptor distinct from that which responds to inositol trisphosphate (Section 14.4.1). The responses to cADP-rihose and NAADP are additive, and they seem to act on different intracellular calcium stores (Jacohson et al., 1995 Patel et al., 2001). 

Fohr KJ, Scott J, Ahnert-Hilger G et ol. (1989) Characterization of the inositol 1,4,5,-trisphosphate-induced calcium release from permeabilized endocrine cells and its inhibition by decavanadate and p-hydroxymercuribenzoate. Biochem. J. 262 83-89. 

Bootman, M.D., Berridge, M.J. and Roderick, H.L. (2002) Activating calcium release through inositol 1,4,5-trisphosphate receptors without inositol 1,4,5-trisphosphate. Proc.Nad.Acad.Sd. U.S.A, 99, 7320-7322. 

There are some extremely complex interactions in this area. To follow just two examples The Aj activation of phospholipase C causes increased hydrolyis of inositol lipids so that inositol-1,4,5-trisphosphate is produced and can induce calcium release from microsomes. Caffeine can directly inhibit opening of the calcium channel in the microsomes beyond any action it may have on the initial Aj receptor [212, 213], Caffeine acting on hippocampal Ai receptors appears to stimulate release of acetylcholine, but it is actually blocking adenosine receptors that inhibit the release [214, 215]. The end-result is increased wakefulness produced by caffeine. 

Supattopone, P., Danoff, S. K., Theibert, A., et al. 1988). Cyclic AMP-dependent phosphorylation of brain inositol trisphosphate receptor decreases its release of calcium. Proc. Natl. Acad. Sci. U.S.A. 85, 8747-8750. 

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