Thromboxanes roles

Another vasoactive substance produced by the endothelium is thromboxane A2 (TxA2). Normally, small amounts of TxA2 are released continuously however, increased synthesis appears to be associated with some cardiac diseases. Synthesized from arachidonic acid, a plasma membrane phospholipid, TxA2 is a potent vasoconstrictor. Furthermore, this substance stimulates platelet aggregation, suggesting that it plays a role in thrombotic events such as myocardial infarction (heart attack). Nonsteroidal anti-inflammatory drugs such as aspirin and ibuprofen block formation of TxA2 and reduce formation of blood clots. 

Lipids have multiple roles in cells. Recent discoveries show that the same lipid may have both structural and regulatory roles in the cell. For example, while arachidonic acid (20 4co6) is a major constituent of brain inositides and PtdEtn, the free acid is also a precursor of a number of important bio messengers, the eicosanoids, such as prostaglandins, prostacyclins, leukotrienes and thromboxanes... 

Capra, V., Habib, A., Accomazzo, M. R., et al. (2003) Thromboxane prostanoid receptor in human airway smooth muscle cells a relevant role in proliferation. Eur. J. Pharmacol. 474, 149-159. 

Nishimura, H., Tokuyama, K., Inoue, Y., et al. (2001) Acute effects of prostaglandin D-2 to induce airflow obstruction and airway microvascular leakage in guinea pigs role of thromboxane A(2) receptors. Prostaglandins Other Lipid Medial. 66, 1-15. 

Figure 11.31 Effects of endothelial cells, via prostacyclins, and platelets, via thromboxanes, on aggregation of platelets. Aggregation of platelets plays an important role in thrombosis. The drug inhibited COX-2 and hence prostacyclin formation. However, both COX-1 and COX-2 are present in platelets so COX-1 continues to produce thromboxane.

Nagai H, Shimazawa T, Yakuo I, et al. 1989b. The role of thromboxane A2 [Tx/ ] in liver injury in mice. Prostaglandins 38 439- 446. 

T. Kobayashi, Y. Tahara, M. Matsumoto, M. Iguchi, H. Sano, T. Murayama, H. Aral, H. Oida, T. Yurugi-Kobayashi, J.K. Yamashita, H. Katagiri, M. Majima, M. Yokode, T. Kita, S. Narumiya, Roles of thromboxane A(2) and prostacyclin in the development of atherosclerosis in apoE-deficient mice, J. Clin. Invest. 114 (2004) 784. 

Arruzazabala, M. L., V. Molina, D. Carbajal, S. Valdes, and R. Mas. Effect of policosanol on cerebral ischemia in Mongolian gerbils role of prostacyclin and thromboxane A2. Prostaglandins Leuko Essent Fatty Acids 1993 49(3) 695-697. 

PGH2 is the precursor of various prostaglandins and thromboxanes. Each reaction is catalyzed by a separate tissue-specific enzyme as indicated in figure 19.19. The tissue localization of the enzyme relates to the role of the... 

Phospholipase A2 has an important role in the production of arachidonic acid. This is the precursor of some very important signal molecules such as the prostaglandins, prostacyclins, thromboxanes and leukotrienes. Most of the arachidonic acid in cells is attached at the 2-position of certain phospholipids, and is released by the action of phospholipase A2. The role of Ca2+ in the secretion of these signal molecules will be discussed in the next section. 

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