Inositol -trisphosphate Ins

Shoback, D.M., Membreno, L.A., and McGhee, J.G., High calcium and other divalent cations increase inositol trisphosphate in bovine parathyroid cells, Endocrinology 123, 382-389, 1988. 

Yao Y, Choi J, Parker I. Quantal puffs of intracellular Ca evoked by inositol trisphosphate in Xenopus oocytes. J. Physiol. 1995 482 533-553. 

Activation of PLC generates diacylglycerol (DAG) and inositol trisphosphate (Ins(l,4,5)/>3). In contrast with many cells, islet PLC may also be directly... 

I, 4-bisphosphate and inositol 1,4,5-trisphosphate [59,60]. More recent studies, however, have shown that acid conditions are necessary for the extraction of these latter inositol phosphates [238]. With this modification to the experimental protocol it is possible to demonstrate a rapid accumulation of inositol trisphosphate in slices of guinea-pig cerebellum in response to histamine [238]. The rate of accumulation of inositol trisphosphate in this brain region is more rapid than that of the less polar inositol phosphates and the highest rate of accumulation is normally achieved during the first 5 min of... 

Fig. 10. Crystal structure of phosphatidylinositol-PLC5 showing the C2 and catalytic domains. The position of the PH domain that would be attached to the EF-hand domain is indicated. The membrane surface would be parallel to the top surface of the molecule as shown. Calcium ions are shown hound to the active site and to the C2 domain. The position of inositol trisphosphate in space-filling format at the active site is indicated. Adapted from L.-O. Essen (1996) and Ref [32]. (See color plate section, plate no. 10.)...

Europe-Finner, G.N. P.C. Newell. 1987. Cyclic AMP stimulates accumulation of inositol trisphosphate in Dictyostelium. J. Cell Sci. 87 221-9. 

Ito, K. Miyashita, Y. Kasai, H. Kinetic control of multiple forms of Ca(2 +) spikes by inositol trisphosphate in pancreatic acinar cells. J. Cell Biol 1999, 146, 405-413. 

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 inositol is present in ph osphatidylinositol as the stereoisomer, myoinositol (Figure 14—8). Phosphatidylinositol 4,5-hisphosphate is an important constituent of cell membrane phosphohpids upon stimulation by a suitable hormone agonist, it is cleaved into diacylglycerol and inositol trisphosphate, both of which act as internal signals or second messengers. 

Fig. 12. Tentative model of the signal transduction chain that links the perception of pectic fragments to defense responses in carrot cells. Abbreviations apy, heterotrimeric G protein CaM, calmodulin 4CL, 4-coumarate-CoA ligase CTX, cholera toxin FC, fusicoccine GDP-P-S and GTP-y-S, guanosine 5 -0-(2-thiodiphosphate) and guanosine 5 -0-(3-thiotriphosphate) IP3, 1,4,5-inositol trisphosphate PAL, phenylalanine ammonia-lyase PLC, phospholipase C PR, pathogenesis related PTX, pertussis toxin Rc, receptor SP, staurosporine. Activation and inhibition are symbolized by + and -respectively.

Wekesa K. and Anholt R. (1997). Pheromone regulated production of inositol-(l,4,5)-trisphosphate in the mammalian vomeronasal organ. Endocrinology 138, 3497-3504. 

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. 

JD Johnson, JC Garrison. (1987). Epidermal growth factor and angiotensin II stimulates formation of inositol 1,4,5 and inositol 1,3,4-trisphosphate in hepatocytes. J Biol Chem 262 17285-17293. 

Tanimura, A., Nezu, A., Morita, T., Turner, R. J. and Tojyo, Y. (2004). Fluorescent biosensor for quantitative real-time measurements of inositol 1,4,5-trisphosphate in single living cells. J. Biol. Chem. 279, 38095-8. 

The other activity associated with transmembrane receptors is phospholipase C. Phosphatidyl inositol is a membrane phospholipid that after phosphorylation on the head group is found in the membrane as a phos-photidylinostitol bis phosphate. Phospholipase C cleaves this into a membrane associated diacylglycerol (the lipid part) and inositol trisphosphate (IP3, the soluble part). Both play a later role in elevating the level of the second messenger, Ca2+. 

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). 

Rosel, P, Arranz, B., San, L. et al. Altered 5-HT2A binding sites and second messenger inositol trisphosphate (IP3) levels in hippocampus but not in frontal cortex from depressed suicide victims. Psych. Res. Neuroimag. 99 173-181,2000. 

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... 

Swatton JE, Morris SA, Cardy TJA, Taylor CW 1999 Type 3 inositol trisphosphate receptors in RINm5F cells are biphasically regulated by cytosolic Ca2+ and mediate quantal Ca2+ mobilization. Biochem j 344 55—60... 

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... 

Chadwick CC, Saito A, Fleischer S 1990 Isolation and characterization of the inositol trisphosphate receptor from smooth muscle. Proc Nad Acad Sci USA 87 2132-2136 Chambers P, Neal DE, Gillespie JI1999 Ryanodine receptors in human bladder smooth muscle. 

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