Arachidonic acid release

Functionally, the Dl-like receptors (Dl, D5) are coupled to the G protein Gas and thus can stimulate adenylyl cyclase. The D2-like receptors (D2, D3, and D4) couple to pertussis toxin sensitive G proteins (Gai/0), and consequently inhibit adenylyl cyclase activity. While the Dl-like receptors almost exclusively signal through Gas-mediated activation of adenylyl cyclase, the D2-like receptors have been reported to modulate the activity of a plethora of signaling molecules and pathways. Many of these actions are mediated through the G(3y subunit. Some of these molecules and pathways include the calcium channels, potassium channels, sodium-hydrogen exchanger, arachidonic acid release, and mitogen-activated protein kinase pathways. 

Shanker G, Mutkus LA, Walker SJ, Aschner M. 2002. Methylmercury enhances arachidonic acid release and cytosolic phospholipase A2 expression in primary cultures of neonatal astrocytes. Brain Res Mol Brain Res 106 1-11. 

Braughler, J.M., Chase, R.L., NefF, G.L., Yonkers, P.A., Day, J.S., HaU, E.D., Sethy, V.H. and Lahti, R.A. (1988). A new 21-amino steroid antioxidant lacking glucocorticoid activity stimulates ACTH secretion and blocks arachidonic acid release from mouse pituitary tumor (ArT-20) cells. J. Pharmacol. Exp. Ther, 244, 423-427. 

Free radicals are by-products of prostaglandin metabolism and may even regulate the activity of the arachidonate pathway. Arachidonic acid, released from lipids as a result of activation of phospholipases by tissue injury or by hormones, may be metabolized by the prostaglandin or leu-kotriene pathways. The peroxidase-catalysed conversion of prostaglandin G2 to prostaglandin H2 (unstable prostanoids) and the mechanism of hydroperoxy fatty acid to the hydroxy fatty acid conversion both yield oxygen radicals, which can be detected by e.s.r. (Rice-Evans et al., 1991). 

Levine L (2003b) Tamoxifen stimulates arachidonic acid release from rat liver cells by an estrogen receptor-independent, non-genomic mechanism. BMC Cancer 3(1) 24... 

The G-protein that has been termed Gp, and that is linked to phospholipase C activation, may in fact be Gaj 2 or Gc. 3. Ga is designated as the G-protein responsible for activation of phospholipase A2, which results in arachidonic acid release. Some experimental evidence indicates that, at least in HL-60 cells, different agonists can preferentially activate different phospholipases, and some of these are responsible for the activation of secretion. In neutrophils, the two pertussis-toxin-sensitive Ga-proteins (Gaj-2 and G j 3) have been identified by peptide mapping of proteolytic digests of the proteins, by peptide sequencing and by immunoblotting. Complementary-DNA clones for the mRNA of these two molecules have also been isolated from an HL-60 cDNA library. Gai-2 is five to ten times more abundant than Gai.3, the former component comprising 3% of the total plasma membrane proteins. It is possible that these two different Ga-subunits are coupled to different phospholipases (e.g. phospholipases C and D). Pertussis toxin inhibits the secretion of O2 after stimulation of neutrophils by fMet-Leu-Phe, but pertussis-toxin-insensitive G-proteins are also present in neutrophils. These may be members of the Gq family and may be involved in the activation of phospholipase Cp (see 6.3.1). 

Exposure of neutrophils to heat shock also results in the synthesis of HSPs and a decrease in their ability to generate reactive oxidants. This is not due to cell death, because the response is reversible and other cellular functions are unaffected. For example, after 20 min exposure at 45 °C, the NADPH oxidase is non-functional, but arachidonic acid release is 73% of control values and PGE2 formation is unaffected. Oxidase activity returns to normal levels 150 min later. Several HSPs are synthesised (e.g. hsp70 and hsp85 at 41 °C, hsp48 and hsp60-65 at 43 °C). (The hsp numbers refer to the relative molecular masses of the proteins.)... 

Prostaglandins are a subgroup of a larger family of compounds known collectively as eicosanoids, which are synthesized from arachidonic acid (arachidonate) this is a 20-carbon omega-6 unsaturated fatty acid (C20 4). The source of the arachidonic acid for PG synthesis is the cell membrane. Most membrane phospholipids have an unsaturated fatty acid as arachidonate at carbon 2 on the glycerol backbone to help maintain membrane fluidity. The arachidonic acid released from the membrane by the... 

Pharmacological approaches include the inhibition of release of arachidonic acid by inhibition of phospholipase A2 and the inhibition of acylcarnitine transferase I by and oxfenicine, the latter of which has been shown to prevent or at least delay ischemia-induced uncoupling. There are at present no data available on the possible effects of inhibitors of arachidonic acid release on ischemia-induced uncoupling. 

Garcia, M., Sakamoto, K., Shigekawa, M., Nakanishi, S., Ito, S. Multiple mechanisms of arachidonic acid release in Chinese hamster ovary cells transfected with cDNA of substance P receptor, Biochem. Pharmacol. 1994, 48, 1735-1741. 

Initial biochemical studies indicate that agonist binding was regulated by guanyl nucleotides, implying that the receptor belongs to the superfamily of receptors coupled to G proteins. In addition, various intracellular responses were found to be associated with Hi-receptor stimulation inositol phosphate release, increase in Ca2+ fluxes, cyclic AMP or cyclic GMP accumulation in whole cells and arachidonic acid release [1],... 

Tordera M, Ferrandiz ML, Alcaraz MJ. 1994. Influence of anti-inflammatory flavonoids on degradation and arachidonic acid release in rat neutrophils. Z Naturforsch [C] 49 235-240. 

Axelrod J. (1990). Receptor-mediated activation of phospholipase A2 and arachidonic acid release in signal transduction. Biochem. Soc. Trans. 18 503-507. 

Farooqui A. A., Ong W. Y., Lu X. R., Halliwell B., and Horrocks L. A. (2001). Neurochemical consequences of kainate-induced toxicity in brain involvement of arachidonic acid release and prevention of toxicity by phospholipase A2 inhibitors. Brain Res. Rev. 38 61-78. 

Lazarewicz J. W., Wroblewski J. T., and Costa E. (1990). N-methyl-D-aspartate-sensitive glutamate receptors induce calcium-mediated arachidonic acid release in primary cultures of cerebellar granule cells. J. Neurochem. 55 1875-1881. 

Monoamine oxidase, tyrosine hydroxylase, and L-amino acid oxidase generate hydrogen peroxide as their reaction product. Hydrogen peroxide is also produced by auto-oxidation of catecholamines in the presence of vitamin C. Moreover, phospholipase A2 (PLA2), cyclooxygenase (COX), and lipoxygenase (LOX), the enzymes associated with arachidonic acid release and the arachidonic acid cascade,... 

Carlstedt-Duke, J., Bronnegard, M., and B. Strandvik, 1986, Pathological regulation of arachidonic acid release in cystic fibrosis the putative basic defect. Proc Natl Acad Sci USA. 83(23) 9202-6. 

Croxtall, J.D., Choudhury, Q., and RJ. Flower, 1998, Inhibitory effect of peptides derived from the N-terminus of lipocortin 1 on arachidonic acid release and proliferation in die A549 cell line identification of E-Q-E-Y-V as a crucial component Br J Pharmacol. 123(5) 975—83. 

Strandvik, B., Bronnegard, M., Gilljam, H., and J, Carlstedt-Duke, 1988, Relation between defective regulation of arachidonic acid release and symptoms in cystic fibrosis. Scand J Gastroenterol Suppl. 143 1-4. 

Arachidonic acid released from membrane phospholipids or other sources is metabolized by the LO pathway to the smooth muscle contractile and vasoactive leukotrienes (LT), LTC4, and LTD4, as well as to the potent chemoattractant LTB4. These molecules are intimately involved in inflammation, asthma, and allergy, as well as in other multiple physiological and pathological processes. For example, cirsiliol (3, 4, 5-trihydroxy-6,7-dimethoxyflavone) proved to be a potent inhibitor of 5-LO (IC50, 0.1 pM) derived from basophilic leukemia cells and peritoneal polymorphonuclear leukocytes. 

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