Arachidonic release, inositol phospholipids

Lynch M. A. and Voss K. L. (1990). Arachidonic acid increases inositol phospholipid metabolism and glutamate release in synaptosomes prepared from hippocampal tissue. J. Neurochem. 55 215-221. 

Rather than being reincorporated into inositol phospholipids, DAG can be broken down to release some arachidonate which is the precursor of prostaglandin E which, in turn, can react with plasma membrane receptors linked to adenyl cyclase and cAMP production. IL-3 does not activate phospholipase C but does promote phosphorylation of the glucose transporter by phosphokinase C (Dexter and Spooner, 1987). 

Kanterman RY, Felder CC, Brenneman DE, Ma AL, Fitzgerald S, Axelrod J. arAdrenergic receptor mediates arachidonic-acid release in spinal-cord neurons independent of inositol phospholipid turnover. J Neurochem 1990 54 1225-1232. 

GU-7, a 3-arylcoumarin derivative, has been isolated fi om Glycyrrhizae radix, which is a crude herbal medicine. GU-7 caused inhibition of platelet aggregation, phosphorylation of 40K and 20K dalton proteins, inositol 1,4,5-trisphosphate production, intraplatelet calcium increase and phosphodiesterase activity in vitro. The data indicate that GU-7 inhibits platelet aggregation by increasing intraplatelet cAMP concentration. Antiplatelet action may also explain the mechanism by which traditional medicines are effective in diabetic neuropathy [236]. Osthole causes hypotension in vivo, and inhibits platelet aggregation and smooth muscle contraction in vitro. It may interfere with calcium influx and cyclic nucleotide phosphodiesterases [12]. Cloricromene, a synthetic coumarin derivative, also possesses antithrombotic-antiplatelet activity [237]. Some of these properties of cloricromene have been attributed to the inhibition of arachidonate release from membrane phospholipids [12]. 

Takenawa, T., Ishitoya, J. and Nagai, Y. (1986). Inhibitory effect of prostaglandin E2, forskolin, and dibutyryl cAMP on arachidonic acid release and inositol phospholipid metabolism in guinea pig neutrophils. ]. Biol Chem., 261, 1092-1098... 

Nakamura T, Ui M (1985) Simultaneous inhibitions of inositol phospholipid breakdown, arachidonic acid release and histamine secretion in mast cells by islet-activating protein, pertussis toxin. A possible involvement of the toxin-specific substrate in the Ca -mobilizing receptor-mediated biosignaling system. J Biol Chem 260 3584-3593... 

The dietary precursor of the eicosanoids is the essential fatty acid, linoleic acid. It is elongated and desaturated to arachidonic acid, the immediate precursor of prostaglandins, which is stored in the membrane as a component of a phospholipid—generally phosphatidyl-inositol (PI). Arachidonic acid is released from PI by phospholipase A2. 

Arachidonic acid, a 20-carbon fatty acid, is the primary precursor of the prostaglandins and related compounds (see Figure 39.3). Arachidonic acid is present as a component of the phospholipids of cell membranes, primarily phosphatidyl inositol and other complex lipids.1 Free arachidonic acid is released from tissue phospholipids by the action of phospholipase A2 and other acyl hydrolases, via a process controlled by hormones and other stimuli (see Figure 39.3). There are two major pathways in the synthesis of the eicosanoids from arachidonic acid (see Figure 39.3). 

The arachidonic acid present in membrane phospholipids is released from the lipid bilayer as a consequence of the activation of membrane-bound phospholipase A2 or C (see Fig. 33.31 and Fig. 35.2). This activation occurs when a variety of stimuli (agonists), such as histamine and the cytokines, interact with a specific plasma membrane receptor on the target cell surface. Phospholipase A2 is specific for the sn-2 position of phosphoacylglycerols, the site of attachment of arachidonic acid to the glycerol moiety. Phospholipase C hydrolyzes phosphorylated inositol... 

A correlation between the metabolism of arachidonic acid and phosphatidyl inositol has been observed in platelets, where this phospholipid appears to be the donor of the arachidonic acid which is released after stimulation with aggregating agents (Schoene lacono, 1976). 

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