From the Guidelines
The prostaglandin production pathway begins with the release of arachidonic acid from cell membrane phospholipids by phospholipase, which is then converted to prostaglandin H2 (PGH2) by cyclooxygenase enzymes (COX-1 and COX-2) as shown in the most recent and highest quality study 1. The pathway involves the following steps:
- Arachidonic acid is liberated from membrane phospholipids by phospholipase
- Arachidonic acid is converted to prostaglandin H2 (PGH2) by cyclooxygenase enzymes (COX-1 and COX-2)
- PGH2 is then converted to various prostaglandins, including PGE2, PGF2α, PGD2, PGI2 (prostacyclin), and thromboxane A2, through the action of specific synthases
- These prostaglandins have distinct physiological functions and are involved in various processes, including inflammation, pain, and fever The cyclooxygenase enzymes (COX-1 and COX-2) are the target of non-steroidal anti-inflammatory drugs (NSAIDs) like ibuprofen and aspirin, which inhibit these enzymes to reduce prostaglandin synthesis and thereby decrease inflammation, pain, and fever, as described in 1 and supported by earlier studies such as 1. The prostaglandin production pathway is crucial for comprehending both normal physiological processes and the mechanism of action of common medications, and understanding this pathway is essential for making informed decisions in clinical practice, particularly in the context of using NSAIDs and aspirin 1.
From the FDA Drug Label
The mechanism of action of celecoxib capsules are believed to be due to inhibition of prostaglandin synthesis, primarily via inhibition of COX-2. Prostaglandins sensitize afferent nerves and potentiate the action of bradykinin in inducing pain in animal models. Prostaglandins are mediators of inflammation. Since celecoxib is an inhibitor of prostaglandin synthesis, its mode of action may be due to a decrease of prostaglandins in peripheral tissues.
The prostaglandin production pathway involves the synthesis of prostaglandins, which are mediators of inflammation. The pathway is inhibited by COX-2 inhibition, which is the mechanism of action of celecoxib. Key points about the pathway include:
- Prostaglandin synthesis: inhibited by celecoxib
- COX-2: primarily involved in the inhibition of prostaglandin synthesis
- Prostaglandins: sensitize afferent nerves, potentiate the action of bradykinin, and mediate inflammation 2
From the Research
Prostaglandin Production Pathway
The prostaglandin production pathway involves several steps and enzymes. The key steps are:
- Arachidonic acid release from membrane phospholipids by phospholipase A2 3, 4, 5, 6
- Conversion of arachidonic acid to prostaglandin H2 by prostaglandin synthase (also known as cyclooxygenase) 3, 4, 5
- Prostaglandin H2 is then converted to various prostaglandins, such as PGD2, PGE2, and PGF2 5
Enzymes Involved
The enzymes involved in the prostaglandin production pathway are:
- Phospholipase A2 (PLA2), which releases arachidonic acid from membrane phospholipids 3, 4, 5, 6
- Prostaglandin synthase (cyclooxygenase), which converts arachidonic acid to prostaglandin H2 3, 4, 5
- Cyclooxygenase (COX) isoenzymes, including COX-1, COX-2, and COX-3, which have different functions and expressions 5
Pathways
There are two main pathways for prostaglandin synthesis:
- Intracellular pathway, where arachidonic acid is released and converted to prostaglandin H2 by prostaglandin synthase-2 3
- Transcellular pathway, where secretory phospholipase A2 (sPLA2) mobilizes arachidonic acid from distal cells, which is then converted to prostaglandin H2 by prostaglandin synthase-1 3
Inhibitors
Several inhibitors of the prostaglandin production pathway have been identified, including: