Arachidonic acid mobilization

Bianco, I. D., Balsinde, J., Beltramo, D. M., Castagna, L. F., Landa, C. A., and Dennis, E. A. (2000). Chitosan-induced phospholipase A2 activation and arachidonic acid mobilization in P388D, macrophages. FEBS Lett. 466, 292-294. 

Feinstein M. B. and Halenda S. P. (1988). Arachidonic acid mobilization in platelets The possible role of protein kinase C and G-proteins. Experientia 44 101-104. 

Balboa M. A., Perez R., and Balsinde J. (2003). Amplification mechanisms of inflammation Paracrine stimulation of arachidonic acid mobilization by secreted phospholipase A2 is regulated by cytosolic phospholipase A2-derived hydroperoxyeicosatetraenoic acid. J. Immunol. 

MA Balboa, J Balsinde, EA Dennis. Involvement of phosphatidate phosphohydrolase in arachidonic acid mobilization in human amnionic WISH cells. J Biol Chem 273 7684-7690, 1998. 

Luo, M., Flamand, N., and Brock, T.G., Metabolism of arachidonic acid to eicosanoids within the nucleus, Biochim. Biophys. Acta 1761, 618-625, 2006 Balboa, M.A. and Balsinde, J., Oxidative stress and arachidonic acid mobilization, Biochim. Biophys. Acta 1761, 385-391, 2006. 

E. Interleukin-1 stimulates prostacyclin production by cultured human endothelial cells by increasing arachidonic acid mobilization and conversion. Arteriosclerosis 10, 129-134... 

Shivachar AC, Martin BR, and Ellis EF (1996) Anandamide- and delta9-tetrahydrocannabinol-evoked arachidonic acid mobilization and blockade by SR141716A [N-(Piperidin-l-yl)-5-(4-chlorophenyl)-l-(2,4-dichlo-rophenyl)-4-methyl-lH-pyrazole-3-carboximide hydrochloride]. Biochem Pharmacol 51 669-676. 

Balsinde, J, Winstead, MV and Dennis, EA (2002) Phospholipase A(2) regulation of arachidonic acid mobilization. FEBS Lett, 531, 2-6. 

Table 2.4. Select inhibitors of arachidonic acid mobilization... 

Balsinde J, Barbour SE, Bianco I, Dennis EA. Arachidonic acid mobilization in P3881Di macrophages is controlled by two distinct phospholipase A2 enzymes. Proc Natl Acad Sci USA 1994 91 11060-11064. 

Berridge MJ 1997 Elementary and global aspects of calcium signalling. J Physiol 499 291—306 Broad LM, Cannon TR, Taylor CW 1999 A non-capacitative pathway activated by arachidonic acid is the major Ca2+ entry mechanism in rat A7r5 smooth muscle cells stimulated with low concentrations of vasopressin. J Physiol 517 121-134 Byron KL, Taylor CW 1995 Vasopressin stimulation of Ca2+ mobilization, two bivalent cation entry pathways and Ca2+ efflux in A7r5 rat smooth muscle cells. J Physiol 485 455—468... 

Neutrophil membranes contain inositol lipids, which comprise about 5-6% of the total membrane lipids. About 80% of these inositol lipids possess stearic acid (Cl8 0) at Cl and arachidonic acid (C20 4) at C2 positions. Phosphatidylinositol accounts for most of these lipids (90%), with smaller amounts of PIP (6%) and PIP 2 (4%), which are synthesised sequentially by the action of 4- and 5-specific kinases, respectively (see Fig. 6.6). Neutrophil membranes also possess a phosphatidylinositol-specific phospholipase C which cleaves phosphatidylinositol 4,5-bisphosphate (PIP2) into Ins 1,4,5 P3 and DAG (Fig. 6.7). Both PLC-/3(/ 2) and PLC-y (72) families appear to be present in neutrophils. The coupling of receptor occupancy to PLC activation in neutrophils can be through a heterotrimeric G-protein, the mobile subunit of which has been termed G p. Evidence for this G-protein link comes from the following facts ... 

One class of agents which inhibits LT production in stimulated cell systems, but probably not by direct 5-LO inhibition, is the anti-inflammatory corticosteroids, represented by dexamethasone (10) [30-34]. The well-known inhibition of PG production seen with eorticosteroids is not due to direct CO inhibition, but has been attributed to the inhibition of arachidon-ic acid mobilization by phospholipase A2, caused by enhanced biosynthesis of one or more proteins called lipocortins [35] (although this hypothesis is now being seriously questioned [36]). More recent evidence indicates the possibility of down-regulation of CO enzyme levels [37-39] similar mechanisms involving altered gene regulation could be involved in the observed effects on LT production as well. 

Recently, Strivastava [137] has suggested a mechanism for the vitamin s anti-aggregatory action in platelets that does not involve the arachidonic acid cascade system. The author proposed that the inhibition of aggregation could be due to inhibition of intracellular mobilization of Ca2 + from the dense tubular system of the cytoplasm. 

Endothelial cells and the kidneys play probably an important role in the longterm homeostasis as well as in the development of AD. Endothelial cells synthesize and release vasorelaxant and vasoconstrictor substances. The vasoconstrictor mediators, endothelins, were isolated, purified, sequenced, and cloned [100], The human endothelin receptor has seven membrane helices and is apparently G-protein-coupled. Endothelin-induced smooth muscle contraction involves the following processes activation of PLC, PIP2 hydrolysis, generation of 1,4,5-IP3, accumulation of DAG, mobilization of intracellular Ca2+ with facilitation of Ca2+ influx, activation of PKC, activation of PLA2 and arachidonic acid release, activation of PLD, and stimulation of Na+-H+... 

In many cell types, D2 receptor stimulation has an effect on enzymes metabolizing membrane lipids. We have mentioned above that in mesenchyme-derived cells and in striatal neurons, D2 agonists stimulate the activity of PLCp by mobilizing Gpy complex, and produce an inositol triphosphate-dependent Ca2+ release from intracellular stores (Ghahremani et al., 1999). In CHO cells stably transfected with D2 receptors, D2 agonists potently enhance the release of arachidonic acid when intracellular Ca2+ levels are already enhanced. This effect was observed following stimulation of various Gi/o-coupled... 

Using a variety of cell lines, D2R has been shown to couple to numerous G-proteins including Got i, Gai2, Gai3, Ga0 and Gaz. Depending on the cell type and isoform expressed, D2R activation can lead to the inhibition of AC and cAMP production, activation of potassium channels, inhibition of L-type calcium channels, stimulation of PLC activity and calcium mobilization, potentiation of Ca2+-evoked arachidonic acid release, stimulation of Na+/H+ exchange, and regulation of PI hydrolysis (Di Marzo et al., 1993 Mercier et al., 2001). 

Nilsson CL, Hellstrand M, Ekman A, Eriksson E (1998) Direct dopamine D2-receptor-mediated modulation of arachidonic acid release in transfected CHO cells without the concomitant administration of a Ca2+-mobilizing agent. Br J Pharmacol 724 1651-1658. 

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