Inositol 1,4,5-trisphosphate receptor, calcium

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. 

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... 

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. 

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. 

Morris, S. A. Correa, V. Cardy, T. J. A. O Beime, G. Taylor, C. W. Interactions between inositol trisphosphate receptors and fluorescent Ca indicators. Cell Calcium 1999, 25, 137-142. 

This can be illustrated by known interactions between the cAMP and Ca2+ pathways. A first messenger that initially activates the cAMP pathway would be expected to exert secondary effects on the Ca2+ pathway at many levels via phosphorylation by PKA. First, Ca2+ channels and the inositol trisphosphate (IP3) receptor will be phosphorylated by PKA to modulate intracellular concentrations of Ca2+. Second, phospholipase C (PLC) is a substrate for PKA, and its phosphorylation modulates intracellular calcium concentrations, via the generation of IP3) as well as the activity of PKC, via the generation of DAG, and several types of CAMK. Similarly, the Ca2+ pathway exerts potent effects on the cAMP pathway, for example, by activating or inhibiting the various forms of adenylyl cyclase expressed in mammalian tissues (see Ch. 21). 

Boehning, D., Patterson, R. L., Sedaghat, L. et al. Cytochrome c binds to inositol (1,4,5) trisphosphate receptors, amplifying calcium-dependent apoptosis. Nat. Cell Biol. 5 1051-1061, 2003. 

Nelson MT, Patlak JB, Worley JF, Standen NB 1990 Calcium channels, potassium channels, and voltage dependence of arterial smooth muscle tone. Am J Physiol 259 C3-C18 Nixon GF, Mignery GA, Somlyo AV 1994 Immunogold localization of inositol 1,4,5-trisphosphate receptors and characterization of ultrastructural features of the sarcoplasmic reticulum in phasic and tonic smooth muscle. J Muscle Res Cell Motil 15 682-700 Peng H, Matchkov V, Ivarsen A, Aalkjaer C, Nilsson H 2001 Hypothesis for the initiation of vasomotion. CircRes 88 810-815... 

Putney JW Jr 1997 Capacitative calcium entry. Springer-Verlag, Heidelberg Putney JW Jr 1999 TRP, inositol 1,4,5-trisphosphate receptors, and capacitative calcium entry. Proc Natl Acad Sci USA 96 14669-14671... 

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. 

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 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. 

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. 

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. 

Multicomponent Hormonal Systems Facilitate a Great Variety of Responses The Guanylate Cyclase Pathway Calcium and the Inositol Trisphosphate Pathway Steroid Receptors Modulate the Rate of Transcription... 

Bezprozvanny I. 2005 The inositol 1,4,5-trisphosphate receptors. Cell Calcium 38, 261-272. 

Cameron, A. M., Steiner, J. P, Sabatini, D. M., Kaplin, A. I., Walensky, L. D., and Snyder, S. H. (1995a). Immunophilin FK506 binding protein associated with inositol 1,4,5-trisphosphate receptor modulates calcium flux. Proc. Natl. Acad. Sci. U.S.A. 92, 1784-1788. 

The major substrates of All-activated PLC remain a matter of controversy. Purified PLC activated by calcium has been shown to directly hydrolyse PI, PIP and PIP2 in vitro to yield diacylglycerol and, respectively, inositol monophosphate (IPj), inositol bisphosphate (IP2) and inositol trisphosphate (IP3). In intact cells the substrate specificity of receptor-activated PLC has been investigated by monitoring the loss of radiolabeled inositol incorporated into phosphoinositides. In the target tissues under discussion, activation of PLC by All results in an immediate (approx. 15 s) reduction in the levels of PIP2 and PIP and a subsequent loss (approx. 5 min) of PI [26-28]. These losses could result either from the direct PLC-catalysed hy-... 

---