CORE FOUNDATIONS FOR MEDICINE TUTORIAL ON EICOSANOIDS

Prostanoids

Cyclooxygenase-1 (COX-1) or cycloxygenase-2 (COX-2) converts arachidonic acid to the common prostanoid precursor, prostaglandin H.

Other enzymes lead to leukotriene and lipoxin synthesis.

A knowledge of COX-1 and COX-2 is important for understanding the medical aspects of prostanoid action. The essential to know differences between COX 1 and COX 2 are:

Distribution:.

  • Most cells synthesize COX-1.
  • COX-2 is present primarily in:
    • cells that mediate pain, fever and inflammation
    • endothelial cells that line blood vessels
    • the epithelial cells that line the gastrointestinal tract.
Expression:
  • COX-1 and COX-2 are encoded by different genes.
  • COX-1 is synthesized at a relatively constant rate; its synthesis is not induced.
  • COX-2 synthesis is induced by extracellular signals; in cells not receiving these signals, COX-2 is not present or is present in small amounts.
  • Glucocorticoids suppress expression of the COX-2 gene.
COX inhibitors:
  • NSAIDS (non-steroidal anti-inflamatory drugs) other than aspirin inhibit both COX-1 and COX-2.
  • Aspirin inhibits COX-1 and alters the activity of COX-2 (in the presence of aspirin COX-2 produces lipoxin precursors rather than prostaglandin H).
  • Inhibition of COX-2 provides relief from pain, fever and inflammation.
  • Inhibition of COX-1 increases irritation of the stomach lining and decreases blood clotting.
  • Some drugs specifically inhibit COX-2.

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