List 5 types of Eicosanoids
Prostaglandins, Prostacyclins, Thromboxanes, Leukotrienes, Lipoxins
Where are arachidonic acids derived from and by what action are they derived?
Arachidonic acid is released from membrane phospholipids via phopholipase A2.
What is the rate limiting step in prostaglandin synthesis?
Hydrolysis of arachonic acid
How do agents of prostaglandin production function?
Stimulate production by stimulating activity of phosphlipase A2
What is the first prostaglandin product?
PGH2
What are the 2 components of prostaglandin sythesis?
COX (cyclooxygenase) and PG hydroperoxidase (requires GSH)
COX-1 Enzyme
Constitutive (always in constant amount). Found in gastric mucosa, platelets, vascular endothelium, and kidney
COX-2 Enzyme
Inducible. Mainly in activated macrphages/monocytes stimulated by PAF, IL-1, or bacterial lipopolysaccharides. Also in smooth muscle cells. Epithelial/ondothelial cells, and neurons.
What inhibits COX2 induction?
Glucocorticoids
What inhibits COX enzymes?
NSAIDS (more type 2 than 1)
Aspirin’s MOA
inhibits COX1 more than 2. Involves acetylation of the COX enzyme
Steroidal anti-inflammatory drug MOA
inhibit phospholipase A2 activity
Major prostaglandins of blood vessels
PGI2 and PGF2
What is an important inhibitor of platelet aggregation?
PGI2
Major prostaglandin produced by platelets
Thromboxane
Actions of prostaglandins
mediators of inflammation, induce redness and heat, increase capillary permeability, pyrogens activate sythesis of prostaglandins, stimulate uterine contraction, inhibit gastric acid secretion
What are the products of lipoxygenases?
HPETEs
What is another name for HETEs?
leukotrienes
What is the most important product of human lipoxygenases?
5-HPETE, because they are converted into leukotrienes
Important secretory product of leukocytes
Leukotrienes
Leukotrienes’ role in inflammatory disorders
mediates inflammatory disorders
Which leukotrienes increase vascular permeability
LTB4, LTC4, LTD4, LTE4 (B thru E increase permeability)
