Phosphatidylinositol turnover

FIGURE 14-6 Main signaling pathways for histamine receptors. Histamine can couple to a variety of G-protein-linked signal transduction pathways via its four different receptors. The Hj receptor activates the phosphatidylinositol turnover via Gq/11 proteins. The other receptors either positively (H2 receptor) or negatively (H3 and H4 receptor) regulate adenylyl cyclase activity via Gs and GUo protein activation respectively. Several additional signaling pathways have been described, which are not shown. Abbreviations PfP2, phosphatidylinositol 4,5-bisphosphate PIC, phospholipase C AC, adenylyl cyclase ATP, adenosine triphosphate cAMP, cyclic AMP PKC, protein kinase C PICA, protein kinase A. 

An effective treatment for bipolar disorder (manic -depressive illness) is the administration of lithium salts 445/1111-11133 Inhibition of the hydrolysis of inositol phosphate by Li+ (Fig. 11-9) may be related to its therapeutic effect. Reduced phosphatidylinositol turnover may dampen responses to neurotransmitters.1114 Li+ may affect gene expression in neuropeptide-secreting neurons.1115 Bipolar disorder apparently has more than one cause. There are strong indications of genetic susceptibility,1116 and genes that increase susceptibility have been located on chromosomes 4,12,13,18,21, and X.1117... 

Conn PJ, Sanders-Bush E, Hoffman BJ, Hartig PR. A unique serotonin receptor in choroid plexus is linked to phosphatidylinositol turnover. Proc Natl Acad Sci USA 1986 83 4086-4088. 

In the anterior pituitary, stimulation with a GnRH agonist causes an increase in phosphatidylinositol turnover [86—88], After stimulation with GnRH, prelabeled... 

Pike, L.J. and Miller, J.M. (1998) Cholesterol depletion delocalizes phosphatidylinositol bisphosphate and inhibits hormone-stimulated phosphatidylinositol turnover. J. Biol. Chem. 273, 22298-22304. 

Of the effector systems that have been implicated in the transduction mechanisms for opioid receptors, the best studied is opioid inhibition of adenylyl cyclase (see Refs. 69, 97-99 for reviews). Thus binding of an agonist to opioid receptors inhibits the activity of adenylyl cyclase and decreases intracellular cAMP in a number of different tissues. Pertussis toxin sensitivity of opioid inhibition of adenylyl cyclase has been demonstrated in many systems, indicating the involvement of either Gi or Go in the transduction mechanism. Agonist activation of all three types of cloned opioid receptors to inhibit adenyl cyclase has been demonstrated (see Ref 100 and references cited therein). There is also some evidence that (M and 8 opioid receptors can stimulate adenylyl cyclase in certain tissues (see Refs. 69, 97 for reviews). There are conflicting reports on whether k opioid receptors stimulate or inhibit phosphatidylinositol turnover in some tissues (see Ref 100) 8 and fx receptors, however, do not appear to be coupled to phosphatidylinositol turnover in neuroblastoma cell lines NG108-15 and SK-N-SH (101). 

Piericidin Bi N-oxidc inhibited phosphatidylinositol turnover more strongly than piericidin B1 (IC50 = 1.2 pg/ml, 5.0 (xg/ml, respectively). It also displayed activity against gram positive and gram negative bacteria, and fungi, while 38 did not [152],... 

Both 39 and 39a inhibited phosphatidylinositol turnover in the A431 cell assay system, with IC50 = 10.0 pg/ml and 1.1 pg/ml, respectively[154], Piericidin B5 A-oxide was active against gram positive and some gram negative bacteria and fungi piericidin B5 was inactive [154]. 

Phosphatidylinositol turnover was assayed by incorporation of labeled inositol into phospholipids. A431 cells were preincubated in HEPES-buffered saline containing [ H]inositol at 37°C for 30 min. Then, test chemical and EGF were added, and the incubation was continued for 60 min. Subsequently, 10% trichloroacetic acid containing 0.01 M sodium pyrophosphate was added, and the acid-insoluble fraction was scraped off from the dish in H2O. The lipid was extracted from it by the addition of CHCI3 and CH3OH (1 1), and [3r]inositol-labeled lipids were counted by liquid scintillation spectrophotometry. 

Phospholipase C is a rate-limiting enzyme of phosphatidylinositol turnover. Psi-tectorigenin does not inhibit phospholipase C, but we recently found that it inhibits activation of the enzyme by EGF (24). The phospholipase C activity in a homogenate prepared from EGF-treated A431 cells was 4-fold higher than that from untreated cells, and EGF failed to activate the enzyme in the presence of psi-tectorigenin. 

Raymond, V., Leung, P.C.K. and Labrie, F. (1983). Stimulation of PGp2a of phosphatidic acid-phosphatidylinositol turnover in rat luteal cells. Biochem. Biophys. Res. Commm., 116, 39-46... 

The process of lymphocyte activation can be investigated by determining whether or not a particular parameter of activation is prevented by inhibitors of ADPRT. Events that are not inhibited either occur before ADPRT is required or are independent of it. Such changes are the binding of mitogen to the cell surface, the early increase in phosphatidylinositol turnover in the plasma membrane [4], and the early increase in membrane chemiluminescence. Events that are inhibited presumably occur after ADPRT is required. These include the rejoining of DNA breaks (see below), subsequent protein and DNA synthesis [3, 4] and the increased expression of the c-myc gene [11] (Fig. 2). The later response of activated blasts to IL-2 does not appear to involve ADPRT [17]. 

Hess F, Estrugo D, Fischer A et al (2007) Integrin-linked kinase interacts with caspase-9 and -8 in an adhesion-dependent manner for promoting radiation-induced apoptosis in human leukemia cells. Oncogene 26 1372-1384 Hirao M, Sato N, KondoT etal (1996) Regulation mechanism of ERM (ezrin/radixin/moesin) protein/plasma membrane association possible involvement of phosphatidylinositol turnover and Rho-dependent signaling pathway. J Cell Biol 135 37 51... 

Stimulation of phosphatidylinositol turnover by ACh. As shown in Table 2 the slices of caudate nucleus actively incorporate 32pi into the various phospholipids the highest specific radioactivity being achieved by the fraction containing PI plus PS. When the slices were incubated in presence of 10 mM ACh, there was a... 

Kamada, Y. and Muto, S. (1990) Ca " regulation of phosphatidylinositol turnover in the plasma membrane... 

Kishimoto, A, Takai, Y, Mori, T, Kikkawa, U and Nishizuka, Y (1980) Activation of calcium and phospholipid-dependent protein kinase by diacylglycerol its possible relation to phosphatidylinositol turnover. Journal of Biological Chemistry, 255, 2273-2276. 

Morr6 DJ, Gripshover B, Monroe A, Morr6 JT (1984) Phosphatidylinositol turnover in isolated soybean membranes stimulated by the synthetic growth hormone 2,4-dichlorophenoxyacetic acid. 

Holian A. Leukotriene B4 stimulation of phosphatidylinositol turnover in macrophages and inhibition by pertussis toxin. FEBS Lett 1986 201 15-19. 

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