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Aspirin (acetylsalicylic acid) is the most widely used drug in the world.

Arachidonic acid is metabolised by Prostaglandin H Synthase (PGHS) or Cyclooxygenase (COX) to synthesise prostanoids. A homogeneous, enzymatically active cyclooxygenase(COX) or prostaglandin endoperoxide synthase (PGHS) was isolated in 1976 [19]. This membrane-bound hemoprotein and glycoprotein with a molecular weight of 72 kDa is found in greatest amounts in the endoplasmic reticulum of prostanoid-forming cells. Aspirin selectively acetylates the hydroxyl group of one serine residue (Ser 530) located 70 amino acids from the C terminus of the enzyme. Acetylation leads to irreversible COX inhibition. Prostanoids are tissue-specific lipid compounds involved in signalling, and these include Prostaglandin (PG) D2, E2, F2α, Thromboxane A2 (TXA2) and prostacyclin (PGI2). Two major isoforms of PGHS have been identified: COX-1 and COX-2. COX-1 is constitutively expressed in most tissues, while COX-2 is expressed in several tissues, such as vascular endothelium, brain and kidney. COX-1 is the only isoform present in mature platelets and is involved in synthesis of TXA2, which has a central role in platelet aggregation. COX-2 in the vascular endothelium, on the other hand, is involved in PGI2 synthesis. Aspirin irreversibly inactivates both COX-1 and COX-2.

Anti-inflammatory action of aspirin is thought to be mediated through several mechanisms, including sustained inhibition of prostanoid synthesis, inhibition of protein kinase IkBkinase β (IKKβ) in the NF-kB pathway. Analgesic effects of aspirin are thought to be mediated through numerous mechanisms. Aspirin may also contribute to antinociception via: activation of adenosine A(2) receptors (8), inhibiting the inhibitor of NF-kB (IkB) kinase β (thereby preventing translocation of NF-kB) to the nucleus; inhibition of sphingosine-1-phosphate generation; inhibition of α, β-methylene ATP-induced nociception; inhibition of acid-sending ion channels (with high doses of aspirin); acetylation of COX-2 leading to aspirin-triggered lipoxins (e.g., 15-epi-LX A4); promotion of aspirin-triggered DHA pathway.

It has become increasingly evident that arachidonic acid metabolites play a role in the regulation of anterior pituitary hormone secretion, including ACTH. Arachidonic acid is released from esterified stores of cell membrane phospholipids and metabolized to biologically active eicosanoids via three enzyme pathways: to PGs and thromboxanes via cyclooxygenase, to leukotrienes and hydroxyeicosatetraenoic acids by lipoxygenase, and to epoxyeicosatraenoic acids by epoxygenase. PGs modulate cellular responses to various hormones via specific cell receptors and have variable biological activities that are organ and species specific. In vitro studies demonstrate that PGs influence ACTH secretion. PGE2 inhibits ACTH release in response to arginine vasopressin.