Prostaglandin synthesis and COX-enzymes
Because prostaglandins are important pain stimuli and because pharmacological treatment of pain in general practice is focused on prostaglandins, their synthetical pathway and functions are described here.
Synthesis of prostaglandin begins with the conversion of phospholipids from the cell membrane into arachidonic acid (AA). This step involves the enzyme phospholipase A2, which is localised in the membrane. The enzyme cyclo-oxygenase (COX) is responsible for the next step: conversion of AA into prostaglandins. The COX enzyme exists in three isoforms: COX-1, COX-2, and COX-3.
COX-1 enzyme is transcribed from a constitutive household COX-1 gene and is always present. The transcription from the gene is initiated by physiological stimuli. The COX-1 enzyme converts AA into prostaglandins with cytoprotective actions at the level of the kidney, GI tract and platelets. The location of the COX-1 enzyme dictates the function of the prostaglandins it releases:
COX-2 gene is also present in many tissues but the COX-2 enzyme is not always present. Transcription from the gene can be induced in inflammation or tissue damage by stimuli such as cytokines, growth factors and endotoxins. COX-2 converts AA into pro-inflammatory prostaglandins and other inflammatory mediators that increase pain, create edema (swelling) and promote the production of other inflammatory mediators.
The newest isoform is COX-3 - a COX-1 splice variant- and appears to be like COX-1 helping to protect the gastrointestinal tract. It also is unique in that it functions in regulating body temperature.
For an overview of prostaglandin synthesis click here.
Bradykinin indirectly causes pain by activating the phospholipase A2 enzyme in the membrane.
Prostaglandins are NOT present in the synovial fluid in the joints of patients with rheumatoid arthritis.