Inflammation-Prostaglandins and Leukotrienes Flashcards
What type of mediators are PG and LTs?
Eicosanoids
What is the basic biosynthesis of PG?
- -Trigger by cytokine, trauma, ADP, etc causes expression of arachidonic acid
- -Phospholipase A2 causes release of AA, which binds to cyclooxygenase (COX)
- -Formation of PGH2
What are the mechs of action for some of the PGs?
- TxA2: platelet releases it and binds to VSM or other platelets to cause vasoconstriction or aggregation, respectively
- PGI2: endothelial cells release it, binds to VSM or Platelet to cause vasodilation or disaggregation, respectively.
PGF2-alpha: uterus to uterine smooth muscle receptors to cause contraction and parturition
PGD2: Mast cell to lymphocyte or lung epithelial cell to cause chemotaxis or asthma, respectively
PGE2: various cells to spinal neuron (pain), neuron in POA (pyrexia), osteoclast bone resorption), or ovarian cell (ovulation)
What mainly mediates the effects of PGs?
G-protein coupled receptors
Gs- increased cAMP
Gq-increased PLC and Ca2+
Gi- decreased cAMP
What cells are associated with production of leukotrienes?
polymorophonuclear lymphocytes
mast cells
macrophages
What is the basic biosynthesis of leukotrienes?
- -Trigger by immune complex or bacterial peptide causes release of AA
- -5 lipoxygenase (5LO) binds 5 lipoxygenase activator protein (FLAP), activating production of LTA4
- -Production of LTB4 (neutrophil chemoattractant and leukocyte adhesion to endothelial cells) or LTC4 (production of LTD4 or LTE4, causing smooth muscle contraction
What are the MOAs and effects of leukotrienes?
effects mediated by GPPCR
- chemoattractant effects
- neutrophil secretion
- airway smooth muscle contraction
- vascular endothelial cell expression of adhesion molecules
What are some drugs that modify PGs and LTs
NSAIDS: Cox enzyme, anti-inflammatory, analgesic, antipyretic
5LO inhibitors and receptor antags: manage asthma
