Biology Prostaglandins and Eicosanoids

Study Notes

Prostaglandins, thromboxanes, and leukotrienes are collectively known as eicosanoids.
Eicosanoids are 20-carbon compounds derived from arachidonic acid.
Prostanoids include prostaglandins (PGs), prostacyclins (PGIs), and thromboxanes (TXs).
Leukotrienes (LTs) are another class of eicosanoids.
Eicosanoids are potent compounds causing diverse responses, both physiological (inflammation) and pathological (hypersensitivity).
They maintain gastric and renal function, regulate smooth muscle contraction, control blood vessel diameter and platelet homeostasis.
Eicosanoids are not stored and have a short half-life, rapidly metabolized into inactive products.
Prostaglandins (PGs) are the most potent biologically active substances; even a nanogram per milliliter can cause smooth muscle contraction.
Naturally occurring PGs are primarily in the 2 series.
PGs have a very short half-life (around 30 seconds).
PG effects vary across tissues and can even oppose each other.
In most tissues, PGs act as local hormones, increasing cAMP levels.

Prostaglandins are derived from the polyunsaturated fatty acid arachidonic acid, stored in the cell membranes as phospholipids.
Arachidonic acid release is initiated by phospholipase A2 acting on phospholipids.
The next step is the formation of PGH2, the precursor for all prostaglandins, through the oxidative cyclization of free arachidonic acid by PGH synthase.
PGH synthase is a protein in the endoplasmic reticulum membrane.
It has two catalytic activities: fatty acid cyclooxygenase (COX) that needs two oxygen molecules, and peroxidase that depends on reduced glutathione.
PGH2 is then transformed into various prostaglandins and thromboxanes by cell-specific synthases.

Phospholipase (PL) is activated by epinephrine.
Steroids inhibit PL, preventing arachidonic acid release from cell membranes.
Cyclooxygenase is activated by catecholamines but is inhibited by non-steroidal anti-inflammatory drugs (NSAIDs).
Aspirin irreversibly inhibits cyclooxygenase by acetylating a serine residue in its active site.

PGE2 and PGD2 induce inflammation by increasing capillary permeability.
Cortisol and aspirin are strong anti-inflammatory drugs because they inhibit prostaglandin synthesis.
PGE2 reduces T and B cell functions.
PGE2 plays a role in sleep promotion.
Prostacyclin (PGI2) is produced by vascular endothelium and causes vasodilation.
It inhibits platelet aggregation and provides vessel wall protection.
Thromboxane (TXA2) is produced by platelets, leading to vasoconstriction and platelet aggregation.
Prostacyclin and thromboxane activity opposes.
PGF2 stimulates uterine muscles; used for medical termination of pregnancy and to control postpartum hemorrhage.
PGF2 constricts bronchial smooth muscle, while PGE2 is a bronchodilator.
PGE2 is used in aerosols to treat bronchospasm.
PGs in general inhibit gastric secretion and increase intestinal motility.
This inhibitory effect on gastric secretion is used to treat acid peptic disease.
Diarrhea might be a side effect.
PGE2 decreases lipolysis, increases calcium mobilization, and stimulates glycogen synthesis.

LTs are produced from arachidonic acid.
Leukotriene B4 (LTB4) is a potent chemotactic agent, attracting cells to inflammatory sites.
LTB4 is produced by neutrophils.
In structure, the number "4" denotes four double bonds.
LTs cause smooth muscle contraction, constrict bronchioles, increase capillary permeability, activate leukocytes, and cause vasoconstriction.