Eicosanoids Flashcards
Types of eicosanoids
prostanoids
leukotrienes
lipoxins
Types of Prostanoids
Prostacyclin - prostaglandin I2
Prostaglandin
Tromboxanes
Leukotrienes
produced in WBCs
role in inflammation
Types of Leukotrienes
Leukotriene A4: -gatekeeper -divided into B4 or C4 -inhibited by Zileuton Leukotriene B4: -produced by leukocytes -chemoattractant -allows WBC to leave blood vessels Leukotriene C4,D4,E4: -inflammation -bronchoconstriction, vasoconstriction, smooth muscle constriction
Prostacyclin
a prostanoid
role: vasodilator, bronchodilator. prevents platelet activation
Prostaglandins
a prostanoid
role: induce birth, maintain patent PDA, treatment of peptic ulcers, vasodilator, erectile dysfunction, glaucoma
Types of prostaglandins
Prostaglandin H2: -gatekeeper Prostaglandin D2: -made by mast cells -promotes immune cell recruitment -bronchoconstriction, vasodilation Prostaglandin E1: -used in: PDA, erectile dysfunction, limb ischemia -produced from dihomo-gamma-linolenic acid Prostaglandin E2: -vasodilator, bronchoconstrictor -increase body temperature -mucous formation, HCO3- secretion, mucosal blood flow, epithelial regeneration Prostaglandin F2a
Tromboxanes
a prostanoid Thromboxane A2 -produced by activated platelets -short half life -role: activates other platelets, platelet aggregation. vasoconstriction Thromboxane B2: -inactive form
Aspirin
inhibits cyclooxygenases
irreversible acetylatin of a SER
Corticosteroids
inhibits phospholipase A2
COX 1
in cytosol
narrow substrate binding site
PG products secreted
expressed continuously
COX 2
in nuclear membrane
wide binding site
PG products may have nuclear targets
induced in inflammation and physiological imbalance
Lipoxins
anti-inflammatory
receptors:
-agonist on their specific G protein receptor ALX
-antagonist on CysLT receptors
-bind to AhR nuclear receptor - SOCS 2
inhibits:
-neu activation, adhesion, Leu extravasation, synthesis of proinflammatory mediators, ROS production
promote:
-synthesis of anti-inflammatory mediators
-phagocytosis of apoptotic Neu-S
Phospholipids/DAG -> Arachidonic acid
enzyme: Phospholipase A2
inhibited by corticosteroids
Arachidonic acid -> Prostaglandin H2
enzyme: COX1, COX2, peroxidase
- PROSTAGLANDIN D2 SYNTHASE - prostaglandin D2
- PROSTAGLANDIN E SYNTHASE - PG E2 - PG F2
- PROSTACYCLIN SYNTHASE - PG I2
- THROMBOXANE SYNTHASE - thromboxane A2-thromboxane B2