Prostaglandins Overview

Introduction to Prostaglandins

• Prostaglandins were first isolated from prostate gland secretion.
• Initially thought to be hormones from the prostate gland.
• Discovered by Swedish scientist Von Euler, awarded Nobel Prize in the 1970s.

Presence in the Body

• Prostaglandins are found in various tissues:
  • Bone tissue
  • Nerve cells
  • Muscle cells
  • Reproductive tissues (e.g., testes)

Biosynthesis of Prostaglandins

• Source: Derived from arachidonic acid (20-carbon fatty acid).
• Production Location: Synthesized from membrane phospholipids.
• Key Enzyme: Phospholipase A2 releases arachidonic acid from membrane phospholipids.

Steps of Prostaglandin Synthesis

1. Arachidonic Acid Release: Cleavage by Phospholipase A2.
2. Formation of PGG2:
   • Cyclooxygenase activity of Prostaglandin H Synthase incorporates oxygen.
3. Conversion to PGH2:
   • PGG2 is reduced to PGH2 by peroxidase activity of Prostaglandin H Synthase.
4. Diverse Prostaglandins:
   • Various prostaglandins produced from PGH2 via different enzymes:
     • PGI Synthase → Prostaglandin I2 (PGI2)
     • PGD Synthase → Prostaglandin D2 (PGD2)
     • Thromboxane Synthase → Thromboxane A2 (TXA2)

Regulation of Prostaglandin Production

• Key Regulator: Phospholipase A2 activity.
• Positive Regulators:
  • Epinephrine
  • Angiotensin II
  • Vasopressin
• Negative Regulators: Steroids inhibit Phospholipase A2.
• Prostaglandin H Synthase Activity:
  • Triggered by catecholamines.
  • Inhibited by compounds like methyl salicylate and aspirin.

Mechanism of Action

• Prostaglandins act via G-protein coupled receptor signaling pathways.
• Stimulation often results in:
  • Increase in cyclic GMP
  • Activation of protein kinase A
  • Changes in gene expression.

Physiological Functions of Prostaglandins

• Diverse Effects:
  • PGI2: Vascular dilation, prevents platelet aggregation.
  • TXA2: Induces vasoconstriction, promotes platelet aggregation.
  • PGF2: Stimulates uterine muscle contraction (used to induce labor).
  • PGNF: Bronchial smooth muscle contraction.
  • PGE2: Bronchodilation, increases capillary permeability, involved in inflammation.
• Overall Function: Decrease gastric secretions and increase intestinal motility.

Conclusion

• Prostaglandins have complex roles in physiology, including inflammation and reproductive functions.
• Understanding their synthesis and regulation is crucial for comprehending their various physiological effects.

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