Eicosanoids Flashcards
What does eicosanoids stand for?
20 carbon fatty acid
How do Eicosanoids mediate their effects?
Agonists that work with 7-pass transmembrane receptors and heterotrimeric G-proteins
How long is the eicosanoid half-life?
seconds to minutes
What type of signaling do eicosanoids participate in?
Paracrine or autocrine
Name the functions of eicosanoids
Platelet aggregation Inflammation Asthma GI integrity Kidney & liver homeostasis Reproduction Development
What are the major classes of eicosanoids?
Prostacyclins
Prostaglandins
Thromboxanes
Leukotrienes
How many unsaturated bonds does PGE2 have?
2
Describe the generation of COX and 5-LOX eicosanoids
Phosholipase A2 cleaves a membrane phsopholipid into arachidonic acid
arachidonic acid folds and becomes either COX or LOX
What is the major issues with Steroidal anti-inflammatory drugs?
Blocking the production of Phospholipase A2 can cause a loss of GI integrity due to loss of COX-1 production
What are the latin terms for the signs of inflammation?
Rubor (redness)
Tumor (swelling)
Calor (fever)
Dolor (pain)
Why does blocking COX-1 factors cause intestinal ulcers & bleeding?
Survival factors to prevent apoptosis of GI stem cells are produced by COX-1
What is the main function for glucocorticoids?
Increase blood glucose levels for brain function
What triggers the release of glucocorticoids?
Stress
What is the pathway for the release of glucocorticoids?
Stress triggers release of ACTH from pituitary gland
ACTH releases glucocorticoids from adrenal gland
What are the main actions of glucocortcoids?
Inhibition of glucose uptake
Catabolism of proteins
Gluconeogenesis from amino acids
Suppression of immune response
Suppression of inflammation
What effect does COX-1 have on platelets and circulation?
Platelet aggregation
Vasoconstriction
What effects does COX-2 have on platelets and circulation?
Platelet resting
Prevention of unwanted platelet aggregation
Vasodilation
What is the symptom of COX-2 inhibitor toxicity?
Cardiovascular side effects
Unwanted platelet aggregation
What is the advantage of low dose aspirin?
Blocks COX-1 without affecting COX-2 in endothelia
Describe the activity of COX-2 in healthy endothelium
Endothelial cells express COX2
COX2 generates PGI2
PGI2 binds to PGI2 receptors (PI-R) to promote vasodilation and prevent platelet aggregation
PI-R signals by Gs, adenylyl cyclase, cAMP, PKA to activate Ca+ ATPase in SR to keep cytosolic Ca+ low
Low cytosolic Ca+ prevents platelets from changing shape and promotes vasodilation
Describe activity of COX-2 in destroyed endothelium
Platelet adhesion to extracellular matrix stimulates COX-1
COX-1 promotes platelets to produce Thromboxane (TXA2)
TXA2 binds to thromboxane receptors (TP-R) to cause platelet activation,aggregation and vasoconstriction
TP-R signals Gq, phospholipase C, IP3 to release Ca+ from Endoplasmic reticulum
High cytosolic Ca+ initiates changes in platelet shape and promotes vasoconstriction
What type of signaling is thromboxane and platelet aggregation?
Autocrine
What ensures that TXA2 only affects a localized region?
Short half life of 30s
Which eicosanoids is responsible for bronchioconstriction and muscus secretion?
5-LOX
