Platelet arachidonate metabolism

Previously, we reported the effects of Morus flavonoids on arachidonate metabolism in rat platelet homogenates, such as inhibition of 12-hydroxy-5,8,10-heptadecatrienoic acid (HHT), thromboxane B2, and 12-hydroxy -5,8,10,14-eicosatetraenoic acid (12-HETE) [79,80]. As described in the... 

Platelets have been shown to cooperate with leukocytes in production of chemotactic fectors which the cells are unable to synthesize themselves. 12-HETE from platelets are metabolized by unstimulated neutrophils to 12,20-di-HETE (Marcus et al, 1984,1988). Leukocytes produces increased amounts of leukotrienes, because 12-HPETE produced in activated platelets stimulates the activity of leukocyte 5-lipoxygenase (Maclouf et al, 1982 Romano and Sethan, 1992). Neutrophils convert arachidonic acid released from stimulated platelets to produce 5-HETE and leukotriene B4 (LTB ) (Marcus et al, 1982). Platelet activating fector (PAF) are shown to stimulate production of LTB from tiiese cells (Lin et al, 1982). Platelets can also produce the vasoconstrictor leukotriene C4 (LTC4) from leukotriene A4 (LTA4) synthesized by leukocytes (Maclouf and Murphy, 1988). Activated platelets and neutrophils release PAF (Lynch and Henson, 1986) which is a potent mediator of inflammation and asthma. 

Roth 01. (1986). Platelet arachidonic acid metabolism and platelet-activating factor. In Biodiemistry of Platelets (Phillips DR, and Shuman MA Eds.X PP. 69-100, Academic Press Inc. (London) Ltd., Londoa... 

Effects of Natural Products Isolated from Medicinal Plants on Arachidonate Metabolism and Degranulation in Platelets and Leukocytes. 

Fig. (33). Effects of polyacetylene compounds isolated from Saposhnikoviae Radix on arachidonate metabolism in human platelets.

The other sources of the arachidonic acid released by platelets in response to thrombin are phosphatidylcholine and phosphatidylethanolamine (Table 1.1). However, each of these phospholipids exists as three species in platelets, namely as the diacyl-, 1-0-alkyl-, or 1-0-alk-l enyl- forms (Table 1.2). Table 1.2 also shows that l-O-alkyl-2-acyl-PC and l-O-alk-l enyl-2-acyl-PE are enriched in arachidonic acid relative to the other classes of PC or PE, giving rise to the idea that they could serve as important sources of arachidonic acid in stimulated platelets. Purdon and Smith " prelabelled platelets with pH]-arachidonic acid and followed the changes in the different species of PC and PE following thrombin stimulation. It was found that while there was a decrease in radiolabel of both 1,2-diacyl-PC and 1,2-diacyl-PE at all times studied, there was no decrease in the other species of PC or PE, and, indeed, radiolabel in l-O-alkyl-2-acyl-PC and l-0-alk-l -enyl-2-acyl-PE increased at later time points (3-5 min) after thrombin. The thrombin-induced incorporation of arachidonic acid in plasmalogen PE was observed previously by others. Purdon and Smith " concluded that, upon stimulation of human platelets, arachidonic acid is released from both 1,2-diacyl-PC and 1,2-diacyl-PE for metabolism by cyclo-oxygenase and lipoxygenase, while certain other pools of phosphatidylcholine and phosphatidylethanolamine act to collect arachidonic acid. 

Kimura, Y., H. Okuda, T. Nomura, T. Fukai, and S. Arichi Effects of Flavonoids and Related Compounds from Mulberry Tree on Arachidonate Metabolism in Rat Platelet Homogenates. Chem. Pharm. Bull. (Japan) 34,1223 (1986). 

Ajoene was discovered as the most potent platelet inhibitor from an oil-macerated crushed garlic (Apitz-Castro et al 1983), and they revealed that ajoene inhibited both of the arachidonate metabolism and the membrane G-protein level signal transduction of platelets (Apitz-Castro eta/. 1986a, 1986b, 1988). 

Needleman, R, Wyche, A., Raz, A., 1979 Platelet and blood vessel arachidonate metabolism and interactions. J. Clin. Invest. 63, 345-349. 

There is some evidence that in cells with low anandamide amidase activity, such as platelets and neutrophils, anandamide is inactivated by an oxidative pathway involving 12(5)-lipoxygenase (Edgemond, 1998). Metabolism of anandamide by enzymes of the arachidonic acid cascade... 

Srivastava KC. (1984). Aqueous extracts of onion, garlic and ginger inhibit platelet aggregation and alter arachidonic acid metabolism. Biomed Biochim Acta. 43(8-9) S335-46. 

The acid-soluble SH-groups in platelets are mainly those of glutathione (GSH). GSH is a cofactor for enzymes such as peroxidase. If feverfew is able to interfere with this cofactor, enzyme function may be impaired. One pathway that may be affected in this way is the metabolism of arachidonic acid (Figure 6.1). In the presence of feverfew extract an increase was found in lipoxygenase product formation and impaired conversion of HPETE to HETE, for which GSH is a cofactor [52]. Inhibition of the liberation of [ " C]arachidonic acid from phospholipids was also found [53], which implies impairment of phospholipase A2 activity and for which SH-groups are thought to be important. 

Diethylcarbamazine citrate (Hetrazan) is active against several microfilaria and adult filarial worms. It interferes with the metabolism of arachidonic acid and blocks the production of prostaglandins, resulting in capillary vasoconstriction and impairment of the passage of the microfilaria. Diethylcarbamazine also increases the adherence of microfilariae to the vascular wall, platelets, and granulocytes. 

HV051 Sekiya, K., T. Fushimi, T. Kanamori, et al. Regulation of arachidonic acid metabolism in platelets by vegetables. 

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